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Ilhan Y, Balcik OY, Guzel HG, Onder AH, Demir B, Baser MN, Karadag I, Ozbay MF, Genc TB, Uzuntas S, Poyrazoglu O, Beypinar I, Ergun Y, Ozturk B. Novel tumor marker index combining carcinoembryonic antigen and carbohydrate antigen 19-9: New prognostic factor for metastatic colorectal cancer. World J Gastrointest Oncol 2025; 17:104341. [DOI: 10.4251/wjgo.v17.i5.104341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/02/2025] [Accepted: 02/28/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Metastatic colorectal cancer (mCRC) is a global health challenge with a poor prognosis. Prognostic markers are critical for survival prediction.
AIM To evaluate a novel tumor marker index (TMI) combining carcinoembryonic antigen and carbohydrate antigen 19-9.
METHODS This multicenter, retrospective study measured baseline carcinoembryonic antigen and carbohydrate antigen 19-9 levels to calculate a TMI as the geometric mean of values normalized to their upper limits of normal. Receiver operating characteristic curve analysis assessed TMI’s prognostic accuracy, and patients were stratified into high-TMI (≥ 1.39) and low-TMI (< 1.39) groups. The primary endpoint was overall survival (OS), with progression-free survival and treatment response as secondary endpoints.
RESULTS The study included 305 mCRC patients with a median follow-up of 22.9 months. The median OS for high-TMI patients was 29.5 months, significantly lower than the 45.6 months observed in the low-TMI group (P = 0.02). The 2-year OS rates for the high- and low-TMI groups were 59.4% and 72.9%, respectively. Median progression-free survival was also shorter for the high-TMI group (14.0 vs 16.0 months, P = 0.84). High TMI is an independent prognostic factor for worse OS.
CONCLUSION TMI is a simple, cost-effective prognostic tool for mCRC, with high TMI associated with poorer survival outcomes.
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Affiliation(s)
- Yusuf Ilhan
- Department of Medical Oncology, Antalya City Hospital, Antalya 07080, Türkiye
| | - Onur Yazdan Balcik
- Department of Medical Oncology, Alanya Alaaddin Keykubat University, Antalya 07400, Türkiye
| | - Halil Goksel Guzel
- Department of Medical Oncology, Antalya Training and Research Hospital, Antalya 07100, Türkiye
| | - Arif Hakan Onder
- Department of Medical Oncology, Antalya Training and Research Hospital, Antalya 07100, Türkiye
| | - Bilgin Demir
- Department of Medical Oncology, Adnan Menderes University, Aydın 09100, Türkiye
| | - Mehmet Nuri Baser
- Department of Medical Oncology, Adnan Menderes University, Aydın 09100, Türkiye
| | - Ibrahim Karadag
- Department of Medical Oncology, Hitit University, Erol Olcok Education and Research Hospital, Corum 19169, Türkiye
| | - Mehmet Fatih Ozbay
- Department of Medical Oncology, Kırsehir Training and Research Hospital, Kırsehir 40200, Türkiye
| | - Tugrul Burak Genc
- Department of Medical Oncology, Mus State Hospital, Mus 49000, Türkiye
| | - Sahnura Uzuntas
- Department of Internal Medicine, Alanya Alaaddin Keykubat University, Antalya 07425, Türkiye
| | - Oguz Poyrazoglu
- Department of Internal Medicine, Hitit University, Erol Olcok Education and Research Hospital, Corum 19169, Türkiye
| | - Ismail Beypinar
- Department of Medical Oncology, Alanya Alaaddin Keykubat University, Antalya 07400, Türkiye
| | - Yakup Ergun
- Department of Medical Oncology, Bower Hospital, Diyarbakir 21100, Türkiye
| | - Banu Ozturk
- Department of Medical Oncology, Antalya Training and Research Hospital, Antalya 07100, Türkiye
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Asefi M, Rezvani N, Saidijam M, Soltanian AR, Khalilian AR, Mahdavinezhad A. Evaluation of epigenetic silencing of the miR-139-5p gene in the pathogenesis of colorectal cancer and its diagnostic biomarker capability in plasma samples. BMC Cancer 2025; 25:877. [PMID: 40375170 PMCID: PMC12079910 DOI: 10.1186/s12885-025-14290-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 05/08/2025] [Indexed: 05/18/2025] Open
Abstract
BACKGROUND The pathogenesis of CRC requires primary genetic and epigenetic mechanisms including, methylation of CpG islands of the genes. In the current study, micro RNA-139-5p (miR-139-5p) promoter methylated DNA was evaluated in tumor tissue and plasma samples from CRC affected patients. METHODS MiR-139-5p promoter methylation was investigated in 80 samples of tumoral tissue and healthy marginal tissue and the same number of plasma samples, using the MethyLight method. The miR-139-5p expression was assessed using the qPCR method. BT (Bioassay Technology) Elisa kit was applied to measure RAP-1b as a target gene of miR-139-5p. RESULTS Median PMR values of 12.4 (95% CI, 3.23-32.25) and 0.66 (95%CI, 0.51-1.0) were obtained from plasma samples of CRC patients and controls, sequentially. In plasma samples, the sensitivity and specificity of miR-139-5p promoter methylated marker were 75% and 92.5%, in the same order (AUC = 0.958). Lower expression of miR-139-5p in plasma and tumor tissue of patients (P < 0.001) was shown. Also, a significant rise of RAP-1b protein concentration was observed in both mentioned specimens. CONCLUSION Hyper-methylation of miR-139-5p could be suggested as high accuracy diagnostic biomarker for the detection of CRC in plasma samples, pending further validation with large prospective studies.
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Affiliation(s)
- Masoud Asefi
- Research Center for Molecular Medicine, Institute of Cancer, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Nayebali Rezvani
- Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Massoud Saidijam
- Research Center for Molecular Medicine, Institute of Cancer, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ali Reza Soltanian
- Modeling of Noncommunicable Diseases Research Center, Institute of Health Sciences and Technologies, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ali Reza Khalilian
- Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Ali Mahdavinezhad
- Research Center for Molecular Medicine, Institute of Cancer, Hamadan University of Medical Sciences, Hamadan, Iran.
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Yazdanian Z, Mobarra N, Fazel A, Fazeli MS, Ghasemi S, Danesteh S, Khoshrou A, Pakzad R, Raji S, Rafiee M, Akbar S. Ribonucleotide-diphosphate reductase subunit M2 (RRM2) expression and colorectal cancer invasiveness: a potential prognostic biomarker. Mol Biol Rep 2025; 52:447. [PMID: 40332681 DOI: 10.1007/s11033-025-10510-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 04/14/2025] [Indexed: 05/08/2025]
Abstract
BACKGROUND By evaluating serum Ribonucleotide-diphosphate Reductase subunit M2 (RRM2) levels and mRNA tissue expression, we aimed to investigate the potential role of RRM2 as a prognostic biomarker in Colorectal Cancer (CRC) patients. METHODS This descriptive-analytic cohort study was conducted on 50 newly diagnosed CRC patients (stage II, III). Real-time PCR determined the mRNA tissue expression of RRM2. Fifty healthy individuals who came to the hospital of Golestan University of Medical Sciences and Tehran University of Medical Sciences for routine check-ups were considered the control group. Serum RRM2 protein was measured using an ELISA method in the patient group before, one month, and three months after the surgery, and in the control group just on the day of a routine check-up. The tumor metastasis node (TMN) classification system and occurrence of liver metastasis were evaluated in CRC patients. RESULTS The RRM2 gene expression ratio and 95% confidence interval (CI) of the cancerous tissue was 6.56 times higher than the normal tissue (p < 0.001). Blood Sugar level (BS) (p < 0.001) and platelet level (PLT [range 0.004-499 × 103 /mm3]; p = 0.010) were higher in the case group compared with the control group significantly, while Mean Corpuscular Volume (MCV) was significantly lower in the case group (p = 0.015). Overall, the mean serum of RRM2 protein levels in patients was remarkably diminished from before surgery until three months after surgery (p < 0.001). CONCLUSION Serum RRM2 level and mRNA expression were significantly higher among CRC patients which could be considered a biomarker regarding CRC progression.
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Affiliation(s)
- Zahra Yazdanian
- Department of Biochemistry, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Naser Mobarra
- Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Abdolreza Fazel
- Department of Surgery, Sayyad Shirazi Hospital, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mohammad Sadegh Fazeli
- Department of General Surgery, School of Medicine Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Samira Ghasemi
- Department of Biochemistry, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
- Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sina Danesteh
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Alireza Khoshrou
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Pakzad
- Department of Epidemiology, Faculty of Health, Ilam University of Medical Sciences, Ilam, Iran
| | - Sara Raji
- Persian Cohort Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahdi Rafiee
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Soroush Akbar
- Department of Biochemistry, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
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Li C, Zhang W, Chen Q, Xiao F, Yang X, Xiao B, Cheng Y, Qin J, Li X, Wan D, Pan Z, Peng J, Wu X. Development and validation of a logistic regression model for the diagnosis of colorectal cancer. Sci Rep 2025; 15:14759. [PMID: 40295643 PMCID: PMC12037792 DOI: 10.1038/s41598-025-98968-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 04/16/2025] [Indexed: 04/30/2025] Open
Abstract
Colorectal cancer (CRC) diagnosis is challenging due to generalized symptoms. Various biomarker models exist, but their clinical application is limited by low sensitivity and heterogeneous cutoff values. This study aimed to develop and validate a diagnostic model for CRC. Data from 489 patients-337 with CRC and 152 with benign disease-were included. Patients were randomly assigned to training (n = 342) and validation (n = 147) cohorts. Logistic regression identified age (OR 1.06), CA153 (OR 0.26), CEA (OR 4.49), CYFRA 21-1 (OR 5.88), ferritin (OR 0.15), and hs-CRP (OR 0.05) as independent risk factors. Sensitivity and specificity were 88.61% and 82.86% in the training cohort and 90.00% and 76.60% in the validation cohort. Cutoff values for the biomarkers were: CA199, 9.809 U/mL; CA125, 7.743 U/mL; CA153, 6.295 U/mL; CEA, 3.982 ng/mL; CYFRA 21-1, 1.769 ng/mL; ferritin, 163.361 mg/L; hs-CRP, 0.196 mg/L; and serum albumin, 55.966 g/L. The model showed higher sensitivity for early-stage CRC (95.45%, 95% CI 87.2-98.6%) than late-stage CRC (87.27%, 95% CI 76.4-93.5%; P = 0.08). AUCs were 0.907 (training) and 0.872 (validation). The model demonstrated higher sensitivity for early-stage CRC (95.45%) than late-stage CRC (87.27%), underscoring its utility in early detection.
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Affiliation(s)
- Cong Li
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Weili Zhang
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Qichen Chen
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Fei Xiao
- Department of Clinical Laboratory, People's Hospital of Maoming, Maoming, China
| | - Xia Yang
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Binyi Xiao
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Yanshuang Cheng
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Jiayi Qin
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Xueying Li
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Desen Wan
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Zhizhong Pan
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China
| | - Jianhong Peng
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China.
| | - Xiaojun Wu
- Department of Colorectal Surgery, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Yuexiu District, Guangzhou, 510060, China.
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Lindgren M, Ljuslinder I, Jonsson P, Nyström H. Type IV collagen, carcinoembryonic antigen, osteopontin, and hepatocyte growth factor as biomarkers for liver metastatic colorectal cancer. Int J Biol Markers 2025:3936155251329590. [PMID: 40289465 DOI: 10.1177/03936155251329590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
IntroductionDiagnosis and monitoring of metastatic colorectal cancer (mCRC) depend on diagnostic imaging. Circulating carcinoembryonic antigen (CEA) can be analyzed but no optimal, non-invasive biomarker exists. Circulating collagen IV (COL IV) is a promising biomarker in patients with colorectal liver metastases (CLM). This study aimed to evaluate COL IV and other cancer-related and stroma-derived proteins as biomarkers for mCRC.Materials & methodsPlasma COL IV and 10 other proteins were analyzed with ELISA and Luminex multiplex assays.ResultsmCRC patients have elevated levels of circulating COL IV, CEA, interleukin-8 (IL-8), hepatocyte growth factor (HGF), cytokeratin-19 fragments (CYFRA 21-1), osteopontin (OPN), and migration inhibitory factor (MIF) compared to primary CRC (pCRC) patients. COL IV is elevated in mCRC patients compared to healthy individuals. Levels of COL IV, CEA, OPN, CYFRA 21-1, IL-8, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were dependent on the metastatic site. OPN, CEA, and HGF are very good at discriminating between mCRC patients and pCRC controls. COL IV is very good at distinguishing between mCRC patients and healthy controls. The combination of OPN + CEA is superior at detecting mCRC than CEA alone. High HGF and COL IV levels correlate to poor prognosis.ConclusionOPN, CEA, and HGF are potential biomarkers for mCRC. COL IV is a potential biomarker for CLM. The combination of OPN with CEA is superior to CEA alone in detecting mCRC. Levels of circulating proteins depend on metastatic localization, implying that a combination of markers is better than single markers in detecting mCRC disease. High levels of COL IV and HGF have potential prognostic value.
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Affiliation(s)
- Moa Lindgren
- Department of Diagnostics and Intervention/Surgery, Umeå University, SE-901 85, Sweden
| | - Ingrid Ljuslinder
- Department of Diagnostics and Intervention/Oncology, Umeå University, SE-901 87, Sweden
| | - Pär Jonsson
- Department of Chemistry, Umeå University, SE-907 36, Sweden
| | - Hanna Nyström
- Department of Diagnostics and Intervention/Surgery, Umeå University, SE-901 85, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, SE-901 87, Sweden
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Liu C, Liu N, Zhang T, Tu Y. Adoptive immune cell therapy for colorectal cancer. Front Immunol 2025; 16:1557906. [PMID: 40236691 PMCID: PMC11996668 DOI: 10.3389/fimmu.2025.1557906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 02/28/2025] [Indexed: 04/17/2025] Open
Abstract
Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality worldwide, with limited options for patients at advanced stages. Immunotherapy, particularly immune cell-based therapies, has gained significant attention as an innovative approach for targeting CRC. This review summarizes the progress in various immune cell therapies, including DC vaccine, CAR/TCR-T cells, CAR-NK cells et al, each engineered to recognize and attack cancer cells expressing specific antigens. CAR-T cell therapy, which has been successful in hematologic cancers, faces challenges in CRC due to the solid tumor microenvironment, which limits cell infiltration and persistence. CAR-NK cells, CAR-M and CAR-γδ T cells, however, offer alternative strategies due to their unique properties, such as the ability to target tumor cells without prior sensitization and a lower risk of inducing severe cytokine release syndrome. Recent advances in lentiviral transduction have enabled effective expression of CARs on NK and γδ T cells, providing promising preclinical results in CRC models. This review explores the mechanisms, tumor targets, preclinical studies, and early-phase clinical trials of these therapies, addressing key challenges such as enhancing specificity to tumor antigens and overcoming the immunosuppressive tumor microenvironment. The potential of combination therapies, including immune checkpoint inhibitors and cytokine therapy, is also discussed some as a means to improve the effectiveness of immune cell-based treatments for CRC. Continued research is essential to translate these promising approaches into clinical settings, offering new hope for CRC patients.
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Affiliation(s)
- Chenxiao Liu
- Guangdong Province Science and Technology Expert Workstation, Huizhou Central People’s Hospital, Huizhou, Guangdong, China
| | - Nan Liu
- Guangdong Province Science and Technology Expert Workstation, Huizhou Central People’s Hospital, Huizhou, Guangdong, China
- Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China
| | - Tongcun Zhang
- Guangdong Province Science and Technology Expert Workstation, Huizhou Central People’s Hospital, Huizhou, Guangdong, China
- Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China
| | - Yanyang Tu
- Science Research Center, Huizhou Central People’s Hospital, Huizhou, Guangdong, China
- Huizhou Central People’s Hospital Academy of Medical Sciences, Huizhou Central People’s Hospital, Huizhou, Guangdong, China
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Kawahara R, Kautto L, Bansal N, Dipta P, Chau TH, Liquet-Weiland B, Ahn SB, Thaysen-Andersen M. HEXB Drives Raised Paucimannosylation in Colorectal Cancer and Stratifies Patient Risk. Mol Cell Proteomics 2025; 24:100927. [PMID: 39947398 PMCID: PMC11932691 DOI: 10.1016/j.mcpro.2025.100927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 02/08/2025] [Accepted: 02/10/2025] [Indexed: 03/28/2025] Open
Abstract
Noninvasive prognostic markers are needed to improve the survival of colorectal cancer (CRC) patients. Toward this goal, we applied untargeted systems glycobiology approaches to snap-frozen and formalin-fixed paraffin-embedded tumor tissues and peripheral blood mononuclear cells from CRC patients spanning different disease stages and matching controls to faithfully uncover molecular changes associated with CRC. Quantitative glycomics and immunohistochemistry revealed that noncanonical paucimannosidic N-glycans are elevated in CRC tumors relative to normal adjacent tissues. Cell origin-focused glycoproteomics enabled using the well-curated Human Protein Atlas combined with immunohistochemistry of CRC tumor tissues recapitulated these findings and indicated that the paucimannosidic proteins were in part from tumor-infiltrating monocytes (e.g., MPO, AZU1) and of CRC cell origin (e.g., LGALS3BP, PSAP). Biosynthetically explaining these observations, N-acetyl-β-D-hexosaminidase (Hex) subunit β (HEXB) was found to be overexpressed in CRC tissues relative to normal adjacent colorectal tissues and colocalization and enzyme inhibition studies confirmed that HEXB facilitates paucimannosidic protein biosynthesis in CRC cells. Employing a sensitive, quick, and robust enzyme activity assay, we then showed that Hex activity was elevated in plasma and peripheral blood mononuclear cells from patients with advanced CRC relative to controls and those with early-stage disease. Surveying a large donor cohort, the plasma Hex activity was found to be raised in CRC patients relative to normal controls and correlated with the 5-year survival of CRC patients indicating that elevated plasma Hex activity is a potential disease risk marker for patient outcome. Our glycoproteomics-driven findings open avenues for better prognostication and disease risk stratification in CRC.
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Affiliation(s)
- Rebeca Kawahara
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia; Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, Aichi, Japan.
| | - Liisa Kautto
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Naaz Bansal
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Priya Dipta
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - The Huong Chau
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Benoit Liquet-Weiland
- School of Mathematical and Physical Sciences, Macquarie University, Sydney, New South Wales, Australia; Université de Pau et Pays de L'Adour, Laboratoire de Mathématiques et de leurs Applications de PAU, CNRS, E2S-UPPA, Pau, France
| | - Seong Beom Ahn
- Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia
| | - Morten Thaysen-Andersen
- School of Natural Sciences, Macquarie University, Sydney, New South Wales, Australia; Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, Aichi, Japan.
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Guo C, Kumar A, Liao C. Pterostilbene Exhibited the Anticancer Effect Against 1, 2-Dimethylhydrazine (DMH)-Induced Colorectal Cancer via Alteration of Oxidative Stress, Inflammation and Gut Microbiota. J Biochem Mol Toxicol 2025; 39:e70123. [PMID: 40084940 DOI: 10.1002/jbt.70123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/06/2024] [Accepted: 12/21/2024] [Indexed: 03/16/2025]
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. The current investigation aimed to assess the chemoprotective effects of pterostilbene against 1,2-dimethylhydrazine (DMH)-induced colorectal cancer in mice. An in-silico study was conducted to perform docking studies against nuclear factor kappa factor (NF-κB). CRC was induced in mice by administering DMH (20 mg/kg) subcutaneously, and the mice were subsequently administered various dosages of pterostilbene (5, 10, and 15 mg/kg). At the end of the study, various biochemical parameters, including inflammatory cytokines, inflammatory markers, and antioxidant enzymes, were examined. Additionally, the mice's stools were collected for the analysis of intestinal microbiota. A total of 5 hydrogen bonds were identified between NF-κB and pterostilbene using LigPlot+. Pterostilbene significantly (p < 0.001) reduced tumor incidence, tumor weight, and increased body weight. Pterostilbene significantly (p < 0.001) altered the levels of lipid peroxidation, reduced glutathione, superoxide dismutase, glutathione peroxidase, and catalase as well as the activity of both phase I and phase II enzymes. Furthermore, pterostilbene significantly (p < 0.001) decreased the levels of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, interferon-γ, and interleukin-1β, while increasing the levels of anti-inflammatory cytokines like interleukin-4 and interleukin-10. Pterostilbene considerably suppressed the levels of cyclooxygenase-2 and prostaglandin E2, as well as inducible nitric oxide synthase and simultaneously elevated the levels of apoptosis-related parameters, including caspase-3, caspase-8, and caspase-9. Moreover, pterostilbene significantly reduced the abundance of Staphylococcus in the intestinal microbiota and enhanced the levels of beneficial bacteria, such as Bifidobacterium, Akkermansia, and Lactobacillus. Pterostilbene demonstrated a chemoprotective effect against CRC by effectively reducing oxidative stress, mitigating inflammatory responses, and inducing alterations in gut microbiota levels.
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Affiliation(s)
- Chengyun Guo
- Department of Anorectal, Sanmenxia Central Hospital, Henan, China
| | - Ankit Kumar
- Department of Pharmacology, Venkateshwara College of Pharmacy, Meerut, India
| | - Chao Liao
- Department of Anorectal, Ankang Hospital of Traditional Chinese Medicine, Ankang, China
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Hu RH, Yan DY, Zhang KH, Zhang D, Cui XM, Jiang XH, Zhang S. Lipid levels and insulin resistance markers in patients with colorectal cancer: Propensity score matching analysis. World J Gastrointest Oncol 2025; 17:100204. [PMID: 39817133 PMCID: PMC11664609 DOI: 10.4251/wjgo.v17.i1.100204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 10/16/2024] [Accepted: 10/29/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a prevalent malignant neoplasm characterized by subtle early manifestations. AIM To investigate the correlation among serum lipid profiles, the triglyceride-glucose (TyG) index, and the atherosclerotic index (AI) in patients with CRC. Furthermore, it explored the clinical diagnostic utility of combining serum lipids with cancer antigens in the context of CRC. METHODS A retrospective analysis encompassed 277 patients with CRC and 1034 healthy individuals. RESULTS Following propensity score matching, patients with CRC exhibited significantly reduced levels of serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C), as well as a diminished TyG index. Conversely, they displayed elevated AI levels compared to their healthy counterparts. Patients in advanced stages exhibited lower serum levels of TG, TC, and LDL-C compared to those in early stages. Patients with positive lymph node metastasis demonstrated reduced levels of TG, LDL-C, and the TyG index. Receiver operating characteristic analysis revealed that the combination of the TyG index, carcinoembryonic antigen, and carbohydrate antigen 19-9 yielded the highest positive prediction rate for CRC at 75.3%. CONCLUSION Preoperative serum lipid profiles exhibit a robust association with patients with CRC. The concurrent assessment of multiple serum lipids and cancer antigens effectively enhances the diagnostic accuracy for CRC.
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Affiliation(s)
- Ren-Hao Hu
- Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
| | - Dong-Yi Yan
- Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200092, China
| | - Ke-Hui Zhang
- Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
- School of Medicine, Tongji University, Shanghai 200092, China
| | - Di Zhang
- Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
- Department of Emergency Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
| | - Xi-Mao Cui
- Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
| | - Xiao-Hua Jiang
- Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
| | - Shun Zhang
- Department of Gastrointestinal Surgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200120, China
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10
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Filippi A, Deculescu-Ioniță T, Hudiță A, Baldasici O, Gălățeanu B, Mocanu MM. Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer. Int J Mol Sci 2025; 26:631. [PMID: 39859345 PMCID: PMC11766403 DOI: 10.3390/ijms26020631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 01/10/2025] [Accepted: 01/11/2025] [Indexed: 01/27/2025] Open
Abstract
Cancer stem cells (CSC) are known to be the main source of tumor relapse, metastasis, or multidrug resistance and the mechanisms to counteract or eradicate them and their activity remain elusive. There are different hypotheses that claim that the origin of CSC might be in regular stem cells (SC) and, due to accumulation of mutations, these normal cells become malignant, or the source of CSC might be in any malignant cell that, under certain environmental circumstances, acquires all the qualities to become CSC. Multiple studies indicate that lifestyle and diet might represent a source of wellbeing that can prevent and ameliorate the malignant phenotype of CSC. In this review, after a brief introduction to SC and CSC, we analyze the effects of phenolic and non-phenolic dietary compounds and we highlight the molecular mechanisms that are shown to link diets to CSC activation in colon, breast, and prostate cancer. We focus the analysis on specific markers such as sphere formation, CD surface markers, epithelial-mesenchymal transition (EMT), Oct4, Nanog, Sox2, and aldehyde dehydrogenase 1 (ALDH1) and on the major signaling pathways such as PI3K/Akt/mTOR, NF-κB, Notch, Hedgehog, and Wnt/β-catenin in CSC. In conclusion, a better understanding of how bioactive compounds in our diets influence the dynamics of CSC can raise valuable awareness towards reducing cancer risk.
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Affiliation(s)
- Alexandru Filippi
- Department of Biochemistry and Biophysics, “Carol Davila” University of Medicine and Pharmacy of Bucharest, 050474 Bucharest, Romania;
| | - Teodora Deculescu-Ioniță
- Department of Pharmacognosy, Phytochemistry and Phytotherapy, “Carol Davila” University of Medicine and Pharmacy of Bucharest, 050474 Bucharest, Romania;
| | - Ariana Hudiță
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (A.H.); (B.G.)
| | - Oana Baldasici
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuță”, 400015 Cluj-Napoca, Romania;
| | - Bianca Gălățeanu
- Department of Biochemistry and Molecular Biology, University of Bucharest, 050095 Bucharest, Romania; (A.H.); (B.G.)
| | - Maria-Magdalena Mocanu
- Department of Biochemistry and Biophysics, “Carol Davila” University of Medicine and Pharmacy of Bucharest, 050474 Bucharest, Romania;
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11
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Saha S, Ghosh S, Ghosh S, Nandi S, Nayak A. Unraveling the complexities of colorectal cancer and its promising therapies - An updated review. Int Immunopharmacol 2024; 143:113325. [PMID: 39405944 DOI: 10.1016/j.intimp.2024.113325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 10/01/2024] [Accepted: 10/02/2024] [Indexed: 10/30/2024]
Abstract
Colorectal cancer (CRC) continues to be a global health concern, necessitating further research into its complex biology and innovative treatment approaches. The etiology, pathogenesis, diagnosis, and treatment of colorectal cancer are summarized in this thorough review along with recent developments. The multifactorial nature of colorectal cancer is examined, including genetic predispositions, environmental factors, and lifestyle decisions. The focus is on deciphering the complex interactions between signaling pathways such as Wnt/β-catenin, MAPK, TGF-β as well as PI3K/AKT that participate in the onset, growth, and metastasis of CRC. There is a discussion of various diagnostic modalities that span from traditional colonoscopy to sophisticated molecular techniques like liquid biopsy and radiomics, emphasizing their functions in early identification, prognostication, and treatment stratification. The potential of artificial intelligence as well as machine learning algorithms in improving accuracy as well as efficiency in colorectal cancer diagnosis and management is also explored. Regarding therapy, the review provides a thorough overview of well-known treatments like radiation, chemotherapy, and surgery as well as delves into the newly-emerging areas of targeted therapies as well as immunotherapies. Immune checkpoint inhibitors as well as other molecularly targeted treatments, such as anti-epidermal growth factor receptor (anti-EGFR) as well as anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies, show promise in improving the prognosis of colorectal cancer patients, in particular, those suffering from metastatic disease. This review focuses on giving readers a thorough understanding of colorectal cancer by considering its complexities, the present status of treatment, and potential future paths for therapeutic interventions. Through unraveling the intricate web of this disease, we can develop a more tailored and effective approach to treating CRC.
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Affiliation(s)
- Sayan Saha
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| | - Shreya Ghosh
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| | - Suman Ghosh
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| | - Sumit Nandi
- Department of Pharmacology, Gupta College of Technological Sciences, Asansol, West Bengal 713301, India
| | - Aditi Nayak
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India.
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12
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Šarošković M, Vuković M, Stojanoski S, Zorić M, Prvulović Bunović N, Spirovski M, Nosek I. Significance of apparent diffusion coefficient in diagnosis of rectal carcinoma. Front Oncol 2024; 14:1464183. [PMID: 39416464 PMCID: PMC11479860 DOI: 10.3389/fonc.2024.1464183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Accepted: 09/13/2024] [Indexed: 10/19/2024] Open
Abstract
Introduction The apparent diffusion coefficient (ADC) is a quantitative parameter that facilitates the detection and reliable differentiation of rectal cancer. MR differentiation between rectal carcinoma, post-radiation proctitis, and normal rectal wall with the ADC values and their comparison depending on the level of tumor markers and pathohistological characteristics of rectal carcinoma. Methods The retrospective study performed at the Oncology Institute of Vojvodina included 300 patients, 100 each with rectal cancer, post-radiation proctitis, and normal rectum. Mean ADC values were obtained by measuring the region of interest (ROI) of the rectal wall. Results Rectal cancer showed lower ADC values (0.665 ± 0.086 x 10-3mm2/s) compared to both post-radiation proctitis (1.648 ± 0.268 x 10-3mm2/s) and normal rectum (1.180 ± 0.110 x 10-3mm2/s) (p<0.001). No significant differences in ADC values were observed between different grades of rectal cancer (p=0.874; p>0.05), depending on the presence of metastases in the lymph nodes (p=0.357; p>0.05), different TN stage (p=0.196; p>0.05), local spread of the tumor (p=0.312; p>0.05), the presence of RAS mutation (p=0.829; p>0.05) and the value of tumor markers (p=0.923; p>0.05). ADC values below 1.013 x 10-3mm2/s with 100% sensitivity and 96% specificity indicate the presence of rectal cancer in relation to normal wall, with a positive predictive value of 96.1% and a negative of 100%. ADC values below 1.255 x 10-3mm2/s with 100% sensitivity and 95% specificity indicate rectal cancer in relation to post-radiation proctitis. ADC values above 1.339 x 10-3mm2/s with 87% sensitivity and 89% specificity indicate post-radiation proctitis in relation to normal wall. Discussion The ADC is a useful marker in differentiating between rectal cancer, post-radiation proctitis, and normal rectal wall with high sensitivity and specificity, but it cannot be used to distinguish the histological grades of rectal cancer, nor other pathohistological parameters.
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Affiliation(s)
- Milica Šarošković
- Department of Radiology, Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
| | - Miloš Vuković
- Department of Radiology, Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
- Department for Radiology diagnostics, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Stefan Stojanoski
- Department of Radiology, Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
- Department for Radiology diagnostics, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
| | - Milica Zorić
- Department of Radiology, Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
| | - Nataša Prvulović Bunović
- Department for Radiology diagnostics, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
- Department of Nuclear Medicine, Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
| | - Milena Spirovski
- Department for Radiology diagnostics, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
- Department of Oncology, Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
| | - Igor Nosek
- Department of Radiology, Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia
- Department for Radiology diagnostics, Oncology Institute of Vojvodina, Sremska Kamenica, Serbia
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13
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Dimberg J, Shamoun L, af Geijerstam K, Landerholm K, Wågsäter D. Significance of Gene Polymorphism and Gene Expression of BACE2 in Swedish Patients with Colorectal Cancer. Oncology 2024; 103:48-55. [PMID: 39217971 PMCID: PMC11731834 DOI: 10.1159/000540887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION β-site amyloid precursor protein (APP) cleaving enzyme 2 (BACE2) cleaves APP which is ubiquitously expressed in a variety of cell types including cancer cells. BACE2 can process APP in several ways and appears to be involved in the pathogenesis of cancer. Our purpose was to assess the association of mRNA expression and genetic polymorphism of BACE2 in colorectal cancer (CRC) susceptibility and its association to clinicopathological factors in Swedish patients with CRC. METHODS A total of 720 CRC patients and 470 healthy controls were genotyped for BACE2 gene polymorphism rs2012050, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction. Reverse transcription quantitative PCR was used to investigate the BACE2 gene expression in 192 CRC tissue and 181 paired normal tissue. RESULTS Assessing clinicopathological factors, we noted that carrying of T allele in C/T and C/T+T/T was significantly associated with a protective role against disseminated cancer and higher lymph node status. Moreover, individuals carrying T/T genotype were significantly more likely to have poorly differentiated cancer. Follow-up data for patients in poorly differentiated cancer and the Kaplan-Meier analysis showed that the cancer-specific survival curves differed between C/C and C/T+T/T for the BACE2 gene polymorphism and that the carriers of the genotype C/C were associated with more favorable prognosis. We found no significant differences in the genotypic frequencies between the patients and healthy controls. BACE2 mRNA level was significantly 2.2-fold upregulated in CRC tissue when compared to noncancerous tissue. A higher BACE2 mRNA level was observed in smaller tumors and in rectal cancer when compared to colon cancer. CONCLUSION In patients with CRC, our results indicate BACE2 rs2012050 as a useful potential predictor of poor differentiation, disseminated cancer and lymph node status and that the BACE2 mRNA expression is associated to tumor size and cancer location.
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Affiliation(s)
- Jan Dimberg
- Department of Clinical Diagnostics, School of Health and Welfare, Jönköping University, Jönköping, Sweden
| | - Levar Shamoun
- Department of Laboratory Medicine and Pathology, Region Jönköping County, Jönköping, Sweden
| | | | - Kalle Landerholm
- Department of Surgery, Region Jönköping County, Jönköping, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Dick Wågsäter
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
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14
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Fabijanec M, Hulina-Tomašković A, Štefanović M, Verbanac D, Ćelap I, Somborac-Bačura A, Grdić Rajković M, Demirović A, Ramić S, Krušlin B, Rumora L, Čeri A, Koržinek M, Petrik J, Ljubičić N, Baršić N, Barišić K. MicroRNA-193a-3p as a Valuable Biomarker for Discriminating between Colorectal Cancer and Colorectal Adenoma Patients. Int J Mol Sci 2024; 25:8156. [PMID: 39125725 PMCID: PMC11311302 DOI: 10.3390/ijms25158156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 07/16/2024] [Accepted: 07/22/2024] [Indexed: 08/12/2024] Open
Abstract
Specific markers for colorectal cancer (CRC), preceded by colorectal adenoma (pre-CRC), are lacking. This study aimed to investigate whether microRNAs (miR-19a-3p, miR-92a-3p, miR-193a-3p, and miR-210-3p) from tissues and exosomes are potential CRC biomarkers and compare them to existing biomarkers, namely carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9. MiRNA was isolated in the samples of 52 CRC and 76 pre-CRC patients. Expression levels were analyzed by RT-qPCR. When comparing pre-CRC and CRC tissue expression levels, only miR-193a-3p showed statistically significant result (p < 0.0001). When comparing the tissues and exosomes of CRC samples, a statistically significant difference was found for miR-193a-3p (p < 0.0001), miR-19a-3p (p < 0.0001), miR-92a-3p (p = 0.0212), and miR-210-3p (p < 0.0001). A receiver-operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to evaluate the diagnostic value of CEA, CA 19-9, and miRNAs. CEA and CA 19-9 had good diagnostic values (AUCs of 0.798 and 0.668). The diagnostic value only of miR-193a-3p was highlighted (AUC = 0.725). The final logistic regression model, in which we put a combination of CEA concentration and the miR-193a-3p expression level in tissues, showed that using these two markers can distinguish CRC and pre-CRC in 71.3% of cases (AUC = 0.823). MiR-193a-3p from tissues could be a potential CRC biomarker.
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Affiliation(s)
- Marija Fabijanec
- Center for Applied Medical Biochemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia;
| | - Andrea Hulina-Tomašković
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Mario Štefanović
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
- Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia
| | - Donatella Verbanac
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Ivana Ćelap
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
- Department of Clinical Chemistry, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia
| | - Anita Somborac-Bačura
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Marija Grdić Rajković
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Alma Demirović
- Department of Pathology and Cytology “Ljudevit Jurak”, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia; (A.D.); (B.K.)
| | - Snježana Ramić
- Department of Oncological Pathology, University Hospital for Tumors, Sestre Milosrdnice University Hospital Centre, 10000 Zagreb, Croatia;
| | - Božo Krušlin
- Department of Pathology and Cytology “Ljudevit Jurak”, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia; (A.D.); (B.K.)
| | - Lada Rumora
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Andrea Čeri
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Martha Koržinek
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - József Petrik
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
| | - Neven Ljubičić
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia; (N.L.)
| | - Neven Baršić
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia; (N.L.)
| | - Karmela Barišić
- Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia; (M.Š.); (D.V.); (I.Ć.); (A.S.-B.); (M.G.R.); (L.R.); (A.Č.); (M.K.); (J.P.); (K.B.)
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15
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Hitchcock CL, Chapman GJ, Mojzisik CM, Mueller JK, Martin EW. A Concept for Preoperative and Intraoperative Molecular Imaging and Detection for Assessing Extent of Disease of Solid Tumors. Oncol Rev 2024; 18:1409410. [PMID: 39119243 PMCID: PMC11306801 DOI: 10.3389/or.2024.1409410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Accepted: 05/28/2024] [Indexed: 08/10/2024] Open
Abstract
The authors propose a concept of "systems engineering," the approach to assessing the extent of diseased tissue (EODT) in solid tumors. We modeled the proof of this concept based on our clinical experience with colorectal carcinoma (CRC) and gastrinoma that included short and long-term survival data of CRC patients. This concept, applicable to various solid tumors, combines resources from surgery, nuclear medicine, radiology, pathology, and oncology needed for preoperative and intraoperative assessments of a patient's EODT. The concept begins with a patient presenting with biopsy-proven cancer. An appropriate preferential locator (PL) is a molecule that preferentially binds to a cancer-related molecular target (i.e., tumor marker) lacking in non-malignant tissue and is the essential element. Detecting the PL after an intravenous injection requires the PL labeling with an appropriate tracer radionuclide, a fluoroprobe, or both. Preoperative imaging of the tracer's signal requires molecular imaging modalities alone or in combination with computerized tomography (CT). These include positron emission tomography (PET), PET/CT, single-photon emission computed tomography (SPECT), SPECT/CT for preoperative imaging, gamma cameras for intraoperative imaging, and gamma-detecting probes for precise localization. Similarly, fluorescent-labeled PLs require appropriate cameras and probes. This approach provides the surgeon with real-time information needed for R0 resection.
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Affiliation(s)
- Charles L. Hitchcock
- Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, United States
- Actis Medical, LLC, Powell, OH, United States
| | - Gregg J. Chapman
- Actis Medical, LLC, Powell, OH, United States
- Department of Electrical and Computer Engineering, College of Engineering, The Ohio State University, Columbus, OH, United States
| | | | | | - Edward W. Martin
- Actis Medical, LLC, Powell, OH, United States
- Division of Surgical Oncology, Department of Surgery, College of Medicine, The Ohio State University, Columbus, OH, United States
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16
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Mihailović J, Roganović J, Starčević I, Nikolić I, Prvulović Bunović N, Nikin Z. Diagnostic Performance of F-18 FDG PET/CT in the Detection of Recurrent Colorectal Cancer: Correlation with Biochemical Markers and Conventional Imaging Modalities. J Clin Med 2024; 13:3602. [PMID: 38930131 PMCID: PMC11204678 DOI: 10.3390/jcm13123602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/05/2024] [Accepted: 06/10/2024] [Indexed: 06/28/2024] Open
Abstract
Background/Objectives: Although the role of PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of F-18 FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, a retrospective study was performed including 134 CRC patients referred for PET/CT imaging on the suspicion of recurrence, based on elevated CEA and/or CA 19-9 and/or equivocal CIM findings. According to our institution's Tumor Board CRC protocol, after the initial treatment, which was dependent on the TNM stage (neoadjuvant therapy, primary resection, or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy, every six months. The statistics, including univariate and multivariate analyses were conducted using the IBM SPSS 20.0 statistical software. p-values < 0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. PET/CT showed high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA showed a high sensitivity of 98.1% but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy for CA 19-9 and CIM for diagnosis of CRC recurrence were 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p < 0.001), 0.844 (95% CI: 0.772-0.916; p < 0.001), 0.753 (95% CI: 0.612-0.844; p < 0.001), and 0.547 (95% CI: 0.442-0.652; p = 0.358), respectively. Univariate analysis showed that both PET/CT and CIM positive results were highly associated with CRC recurrence (p < 0.001 and p < 0.001, respectively). At the same time, gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) had no significance (p = 0.211, p = 0.158, p = 0.583, and p = 0.201, respectively). Our multivariate analysis showed that independent predictors for CRC recurrence are positive PET/CT scans (p < 0.001), positive CIM results (p = 0.001), and elevated CA 19-9 levels (p = 0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p = 0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting the CRC recurrence (p = 0.023). Conclusions: F-18 FDG PET/CT showed high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the post-operative follow-op in patients with elevated tumor markers.
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Affiliation(s)
- Jasna Mihailović
- Department of Nuclear Medicine, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia;
- Division of Nuclear Medicine, Oncology Institute of Vojvodina, Put dr Goldmana 4, 21204 Sremska Kamenica, Serbia; (J.R.); (I.S.)
| | - Jelena Roganović
- Division of Nuclear Medicine, Oncology Institute of Vojvodina, Put dr Goldmana 4, 21204 Sremska Kamenica, Serbia; (J.R.); (I.S.)
| | - Ivana Starčević
- Division of Nuclear Medicine, Oncology Institute of Vojvodina, Put dr Goldmana 4, 21204 Sremska Kamenica, Serbia; (J.R.); (I.S.)
| | - Ivan Nikolić
- Department of Internal Medicine, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia;
- Clinic for Medical Oncology, Oncology Institute of Vojvodina, Put dr Goldmana 4, 21204 Sremska Kamenica, Serbia
| | - Nataša Prvulović Bunović
- Department of Nuclear Medicine, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000 Novi Sad, Serbia;
- Centre for Diagnostic Imaging, Oncology Institute of Vojvodina, Put dr Goldmana 4, 21204 Sremska Kamenica, Serbia
| | - Zoran Nikin
- Department for Pathoanatomical Diagnostics, Oncology Institute of Vojvodina, Put dr Goldmana 4, 21204 Sremska Kamenica, Serbia;
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17
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Dişçi E, Peksöz R, Laloğlu E, Yıldırgan Mİ, Albayrak Y, Şirin MA, Ağırman E, Atamanalp SS. The Role of Serum Dickkopf1 and CKAP4 Levels in Diagnosing Colorectal Cancer and Measuring the Disease Severity: A Prospective Study. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:933. [PMID: 38929550 PMCID: PMC11205388 DOI: 10.3390/medicina60060933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 05/11/2024] [Accepted: 05/28/2024] [Indexed: 06/28/2024]
Abstract
Background and Objective: Colorectal cancer (CRC) is among the most common types of cancer. Although the disease is treatable in its early stages, five-year survival falls below 20% in the later stages. CEA and CA19-9 are tumor markers used in the diagnosis and follow-up of the disease in clinical practice; however, their diagnostic effectiveness is insufficient. Therefore, the identification of biomarkers that can be easily studied from serum and can diagnose CRC and determine its severity is highly important. In this context, dickkopf1 (DKK1) and cytoskeleton-associated protein 4 (CKAP4) are both promising biomarkers. Materials and Methods: Serum DKK1 and CKAP4 levels were measured in 55 patients with CRC and 40 healthy controls. The patients with CRC were divided into groups based on pathological stages and histological differentiation. The serum levels of both proteins in patients with CRC were measured preoperatively and 10 and 30 days postoperatively. Results: Serum DKK1 and CKAP4 were significantly higher in the CRC group than in the healthy controls (p < 0.05). Serum levels of both proteins rose in line with the disease stage and grade but decreased following surgical resection. A positive correlation was observed between tumor diameter and protein blood levels. The diagnostic efficacy of DKK1 and CKAP4 in CRC (approximately 95%) was higher than that of markers such as CEA and CA19-9. Conclusions: The DKK1 and CKAP4 serum values of patients with CRC are promising biomarkers. They can potentially be used in CRC management, namely, in the diagnosis and treatment of tumor response access and in tumor aggressiveness prediction.
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Affiliation(s)
- Esra Dişçi
- Department of General Surgery, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey; (E.D.); (R.P.); (M.İ.Y.)
| | - Rıfat Peksöz
- Department of General Surgery, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey; (E.D.); (R.P.); (M.İ.Y.)
| | - Esra Laloğlu
- Department Medical Biochemistry, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey
| | - Mehmet İlhan Yıldırgan
- Department of General Surgery, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey; (E.D.); (R.P.); (M.İ.Y.)
| | - Yavuz Albayrak
- Department of General Surgery, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey; (E.D.); (R.P.); (M.İ.Y.)
| | - Mehmet Akif Şirin
- Department of General Surgery, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey; (E.D.); (R.P.); (M.İ.Y.)
| | - Enes Ağırman
- Department of General Surgery, Erzurum City Hospital, Erzurum 25240, Turkey
| | - Sabri Selçuk Atamanalp
- Department of General Surgery, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey; (E.D.); (R.P.); (M.İ.Y.)
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18
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Devalle S, Aran V, Bastos Júnior CDS, Pannain VL, Brackmann P, Gregório ML, Ferreira Manso JE, Moura Neto V. A panorama of colon cancer in the era of liquid biopsy. THE JOURNAL OF LIQUID BIOPSY 2024; 4:100148. [PMID: 40027146 PMCID: PMC11863817 DOI: 10.1016/j.jlb.2024.100148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/13/2024] [Accepted: 03/13/2024] [Indexed: 03/05/2025]
Abstract
Colon cancer (CC) is one of the most frequent cancers worldwide being responsible for over 500 thousand deaths in 2022. Its financial and human burden is expected to increase in the next decades accompanying the growing and aging of the global population. Much of this burden could be alleviated considering that the lethality of CC is mostly due to its late diagnosis and failure in the individualized management of patients. Coordinated government actions and implementation of better diagnostic tools capable of detecting CC earlier and of tracking tumoral evolution are mandatory to achieve a reduction in CC's social impact. CtDNA-based liquid biopsy (LB) has great potential to contribute to patients' screening adhesion, CC earlier detection, and to longitudinal tumor follow-up. In this review, we will discuss the latest epidemiological data on CC disease, diagnostic, subtypes, genetics, and treatment management focusing on the advantages and limitations of ctDNA-based LB, including important bottlenecks and solutions necessary for its clinical translation. The latest ctDNA-directed CC clinical trials will also be examined.
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Affiliation(s)
- Sylvie Devalle
- Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria de Estado de Saúde, Rio de Janeiro, Brazil
| | - Veronica Aran
- Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria de Estado de Saúde, Rio de Janeiro, Brazil
| | | | - Vera Lucia Pannain
- Departamento de Patologia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Paulo Brackmann
- Clínica de Coloproctologia do Hospital Naval Marcílio Dias - IPB/HNMD, Rio de Janeiro, Brazil
| | - Marcelo Leal Gregório
- Instituto de Pesquisas Biomédicas do Hospital Naval Marcílio Dias - IPB/HNMD, Rio de Janeiro, Brazil
| | - José Eduardo Ferreira Manso
- Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Vivaldo Moura Neto
- Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria de Estado de Saúde, Rio de Janeiro, Brazil
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Hajjafari A, Sadr S, Rahdar A, Bayat M, Lotfalizadeh N, Dianaty S, Rezaei A, Moghaddam SP, Hajjafari K, Simab PA, Kharaba Z, Borji H, Pandey S. Exploring the integration of nanotechnology in the development and application of biosensors for enhanced detection and monitoring of colorectal cancer. INORG CHEM COMMUN 2024; 164:112409. [DOI: 10.1016/j.inoche.2024.112409] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2024]
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20
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Kamada T, Ohdaira H, Takahashi J, Aida T, Nakashima K, Ito E, Hata T, Yoshida M, Eto K, Suzuki Y. Novel tumor marker index using carcinoembryonic antigen and carbohydrate antigen 19-9 is a significant prognostic factor for resectable colorectal cancer. Sci Rep 2024; 14:4192. [PMID: 38378762 PMCID: PMC10879146 DOI: 10.1038/s41598-024-54917-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 02/18/2024] [Indexed: 02/22/2024] Open
Abstract
We evaluated the usefulness of a newly devised tumor marker index (TMI), namely, the geometric mean of normalized carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), in determining colorectal cancer (CRC) prognosis. This retrospective cohort study included 306 patients with stages I-III CRC who underwent elective laparoscopic resection between April 2010 and March 2020. Survival rates and risk factors of relapse-free survival (RFS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier curves and Cox proportional hazards model. High-TMI group (122 patients) had significantly lower rates (95% confidence interval [95% CI]) for 5-year RFS (89.7%, 83.9-93.5 vs. 65.8%, 56.3-73.8, p < 0.001) and CSS (94.9%, 89.4-97.6 vs. 77.3%, 67.7-84.4, p < 0.001) than low-TMI group. Multivariate analysis (hazard ratio [95% CI]) indicated ≥ T3 disease (RFS: 2.69, 1.12-6.45, p = 0.026; CSS: 7.64, 1.02-57.3, p = 0.048), stage III CRC (RFS: 3.30, 1.74-6.28, p < 0.001; CSS: 6.23, 2.04-19.0, p = 0.001), and high TMI (RFS: 2.50, 1.43-4.38, p = 0.001; CSS: 3.80, 1.63-8.87, p = 0.002) as significant RFS and CSS predictors. Area under the curve (AUC) of 5-year cancer deaths (0.739, p < 0.001) was significantly higher for TMI than for CEA or CA19-9 alone. Preoperative TMI is a useful prognostic indicator for patients with resectable CRC.
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Affiliation(s)
- Teppei Kamada
- Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan.
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Hironori Ohdaira
- Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan
| | - Junji Takahashi
- Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Takashi Aida
- Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Keigo Nakashima
- Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Eisaku Ito
- Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Taigo Hata
- Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Masashi Yoshida
- Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan
| | - Ken Eto
- Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yutaka Suzuki
- Department of Surgery, International University of Health and Welfare Hospital, 537-3, Iguchi, Nasushiobara, Tochigi, 329-2763, Japan
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21
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Lei X, Zhou D, Wen Y, Sha W, Ma J, Tu X, Zhai K, Li C, Wang H, Tao J, Chen Z, Ruan W, Fan JB, Wang B, Cui C. Cell-free DNA methylation profiles enable early detection of colorectal and gastric cancer. Am J Cancer Res 2024; 14:744-761. [PMID: 38455396 PMCID: PMC10915336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 12/07/2023] [Indexed: 03/09/2024] Open
Abstract
Colorectal cancer (CRC) and gastric cancer (GC) rank the top five common and lethal cancers worldwide. Early detection can significantly reduce the mortality of CRC and GC. However, current clinical screening methods including invasive endoscopic techniques and noninvasive fecal occult blood test screening tests/fecal immunochemical test have shown low sensitivity or unsatisfactory patient's compliance. Aberrant DNA methylation occurs frequently in tumorigenesis and cell-free DNA (cfDNA) methylation has shown the potential in multi-cancer detection. Herein, we aimed to explore the value of cfDNA methylation in the gastrointestinal cancer detection and develop a noninvasive method for CRC and GC detection. We applied targeted methylation sequencing on a total of 407 plasma samples from patients diagnosed with CRC, GC, and noncancerous gastrointestinal benign diseases (Non-Ca). By analyzing the methylation profiles of 34 CRC, 62 GC and 107 Non-Ca plasma samples in the training set (n=203), we identified 40,110 gastrointestinal cancer-specific markers and 63 tissue of origin (TOO) prediction markers. A new integrated model composed of gastrointestinal cancer detection and TOO prediction for three types of classification of CRC, GC and Non-Ca patients was further developed through logistic regression algorithm and validated in an independent validation set (n=103). The model achieved overall sensitivities of 83% and 81.3% at specificities of 81.5% and 80% for identifying gastrointestinal cancers in the test set and validation set, respectively. The detection sensitivities for GC and CRC were respectively 81.4% and 83.3% in the cohort of the test and validation sets. Among these true positive cancer samples, further TOO prediction showed accuracies of 95.8% and 95.8% for GC patients and accuracies of 86.7% and 93.3% for CRC patients, in test set and validation set, respectively. Collectively, we have identified novel cfDNA methylation biomarkers for CRC and GC detection and shown the promising potential of cfDNA as a noninvasive gastrointestinal cancer detection tool.
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Affiliation(s)
- Xiaotian Lei
- Department of Surgery, Zhujiang Hospital, Southern Medical UniversityGuangzhou, Guangdong, China
| | - Dongxun Zhou
- Department of Endoscopy and Gastroenterology, Eastern Hepatobiliary Hospital, Naval Medical University225 Changhai Road, Shanghai, China
| | - Ying Wen
- AnchorDx Medical Co., Ltd.Guangzhou, Guangdong, China
| | - Weihong Sha
- Guangdong Provincial People’s HospitalGuangzhou, Guangdong, China
| | - Juan Ma
- Guangdong Provincial People’s HospitalGuangzhou, Guangdong, China
- Diagnosis and Treatment Center of High Altitude Digestive Disease, Xining Second People’s HospitalXining, Qinghai, China
| | - Xixiang Tu
- AnchorDx Medical Co., Ltd.Guangzhou, Guangdong, China
| | - Kewei Zhai
- The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou, Henan, China
| | - Caixia Li
- Jiyuan Second People’s HospitalJiyuan, Henan, China
| | - Hong Wang
- AnchorDx Medical Co., Ltd.Guangzhou, Guangdong, China
| | - Jinsheng Tao
- AnchorDx Medical Co., Ltd.Guangzhou, Guangdong, China
| | - Zhiwei Chen
- AnchorDx Medical Co., Ltd.Guangzhou, Guangdong, China
- AnchorDx, Inc.Fremont, CA, The United States
| | - Weimei Ruan
- AnchorDx Medical Co., Ltd.Guangzhou, Guangdong, China
| | - Jian-Bing Fan
- AnchorDx Medical Co., Ltd.Guangzhou, Guangdong, China
- AnchorDx, Inc.Fremont, CA, The United States
- Southern Medical UniversityGuangzhou, Guangdong, China
| | - Bin Wang
- Department of Oncology, Changhai Hospital, Naval Medical University168 Changhai Road, Shanghai, China
| | - Chunhui Cui
- Department of Surgery, Zhujiang Hospital, Southern Medical UniversityGuangzhou, Guangdong, China
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22
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Jahani-Sherafat S, Azimirad M, Raeisi H, Azizmohammad Looha M, Tavakkoli S, Ahmadi Amoli H, Moghim S, Rostami-Nejad M, Yadegar A, Zali MR. Alterations in the gut microbiota and their metabolites in human intestinal epithelial cells of patients with colorectal cancer. Mol Biol Rep 2024; 51:265. [PMID: 38302841 DOI: 10.1007/s11033-024-09273-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 01/19/2024] [Indexed: 02/03/2024]
Abstract
BACKGROUND The gut microbiota has become one of the main risk factors for the formation and development of colorectal cancer (CRC). CRC intensification may be due to the microbial pathogens' colonization and their released metabolites. Here, we analyzed Bacteroidetes and Clostridia bacteria in CRC patients and studied bacterial metabolome in cancerous tissues compared to their adjacent normal tissues. METHODS AND RESULTS The population of selected bacteria in biopsy specimens of 30 patients with CRC was studied by RT-qPCR. The mutagenicity and cytotoxicity effects of microbiota metabolites were evaluated by Ames test and MTT Assay, respectively. Moreover, gene expression in carcinogenic pathways was studied by RT-qPCR, and genes with different expressions in tumor and non-tumor tissues were diagnosed. Based on microbiota analysis, the relative abundance of Clostridia and C. difficile was significantly higher in CRC tissue, whereas C. perfringens showed higher relative abundance in normal tissue. AIMES test confirmed the proliferation and mutagenicity effects of the bacterial metabolites in CRC patients. Significant upregulation of C-Myc, GRB2, IL-8, EGFR, PI3K, and AKT and downregulation of ATM were observed in CRC samples compared to the control. CONCLUSIONS The influence of bacterial metabolites on inflammation and altered expression of genes in the cell signaling pathways was observed. The findings confirm the role gut microbiota composition and bacterial metabolites as key players in CRC onset and development.
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Affiliation(s)
- Somayeh Jahani-Sherafat
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St, Velenjak, Tehran, Iran
- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Microbiology Department, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St, Velenjak, Tehran, Iran
| | - Hamideh Raeisi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St, Velenjak, Tehran, Iran
| | - Mehdi Azizmohammad Looha
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sajjad Tavakkoli
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Sharareh Moghim
- Microbiology Department, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Rostami-Nejad
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Celiac Disease and Gluten Related Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Shahid Arabi Ave., Yemen St, Velenjak, Tehran, Iran.
| | - Mohammad Reza Zali
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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23
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Wang H, Shan X, Zhang M, Qian K, Shen Z, Zhou W. Nomograms for predicting overall survival in colorectal cancer patients with metastasis to the liver, lung, bone, and brain. Cancer Causes Control 2023; 34:1059-1072. [PMID: 37486401 DOI: 10.1007/s10552-023-01744-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 06/21/2023] [Indexed: 07/25/2023]
Abstract
BACKGROUND The aim of this study was to identify the heterogeneous and homogeneous prognostic factors associated with distant metastasis to the liver, lung, bone, and brain in colorectal cancer (CRC) patients and then construct nomograms to predict the prognosis. METHODS CRC patients registered in the surveillance, epidemiology, and end results database between 2010 and 2017 were included. A Cox regression model was used to analyse homogeneous and heterogeneous prognostic factors, and Kaplan‒Meier analysis was performed to estimate overall survival (OS). Predictive nomograms were constructed, and their performance was evaluated with C-indexes, calibration curves and the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS A total of 37,641 patients with distant metastasis to the liver, lung, bone, and brain were included. The median survival times of patients with liver metastasis, lung metastasis, bone metastasis, and brain metastasis were 12.00 months (95% CI 11.73-12.27 months), 10.00 months (95% CI 9.60-10.41 months), 5.00 months (95% CI 4.52-5.48 months), and 3.00 months (95% CI 2.28-3.72 months), respectively. An older age, higher N stage, elevated carcinoembryonic antigen level, no surgery at the primary site and no/unknown treatment with chemotherapy were identified as homogeneous prognostic factors for the four types of metastases. The calibration curves, C-indexes and AUCs exhibited good performance for predicting the OS of patients with distant metastases to the liver, lung, bone, and brain. CONCLUSIONS CRC patients with distant metastasis to the liver, lung, bone, and brain exhibited homogeneous and heterogeneous prognostic factors, all of which were associated with shorter survival. The nomograms showed good accuracy and may be used as tools for clinicians to predict the prognosis of CRC patients with distant metastasis.
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Affiliation(s)
- Hongmei Wang
- Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, 400016, China
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, 400016, China
| | - Xuefeng Shan
- Department of Pharmacy, Bishan Hospital of Chongqing Medical University, Chongqing, 402760, China
| | - Min Zhang
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China
| | - Kun Qian
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Zhengze Shen
- Department of pharmacy, Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, China.
| | - Weiying Zhou
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, 400016, China.
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, 400016, China.
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24
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Ibrahim D, Khater SI, Abdelfattah-Hassan A, Alqahtani LS, Metwally AS, Bazeed SM, Elgamal A, Sheraiba NI, Hussein EM, Ali Alasmary F, Salem GA, Ali M, Mahfouz H. Prospects of new targeted nanotherapy combining liponiosomes with berberine to combat colorectal cancer development: An in vivo experimental model. Int J Pharm 2023; 647:123511. [PMID: 37839495 DOI: 10.1016/j.ijpharm.2023.123511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 10/11/2023] [Accepted: 10/12/2023] [Indexed: 10/17/2023]
Abstract
Colorectal cancer (CRC) is one of the most identified and deadly malignancies worldwide. It presents a serious challenge due to its quick growth, which finally culminates in severe malignancy. It is critical to improve the efficacy of berberine (BR) as an anticancer agent to overcome its limited bioavailability. Implementation of a novel, effective nanocarrier system of liponiosomes for BR (LipoNio.BR) can support mechanistic actions associated with its anti-CRC role. Following CRC induction in rats using 1,2 Dimethylhydrazine (40 mg DMH/kg/week), the potency and mechanistic actions of LipoNio.BR were assessed by evaluating the lesion severity and molecular mechanisms controlling oxidative stress, apoptosis, autophagy, and inflammatory responses, and conducting histopathological and immunohistochemistry examinations of colonic tissues. The results indicated that the severity of clinical signs comprising weight gain loss, increased diarrhea and rectal bleeding, and reduced survivability were greatly restored in the LipoNio.BR-treated group. LipoNio.BR remarkably reduced CRC development compared to FBR (free berberine), as it induced apoptosis via upregulating apoptotic genes (Bax and caspase3, increased up to 7.89 and 6.25-fold, respectively) and downregulating the anti-apoptotic gene Bcl-2 by 2.25-fold. LipoNio.BR mitigated the oxidative stress associated with CRC and maintained redox homeostasis. Notably, the excessive inflammatory response associated with CRC was prominently reduced following administration of LipoNio.BR [which decreased iterleukin (IL-B, IL-6), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), proliferating cell nuclear antigen (PCNA), follistatin, and activin BA (beta-A) expression]. LipoNio.BR modulated the expression of nuclear factor kappa B (NF-κB) and mammalian target of rapamycin (mTOR), which impacted tumor vascularity (decreased Vascular endothelial growth factor (VEGF) expression by 2.36-fold). The severity of the histopathological alterations in the colonic tissues, including the development of neoplastic epithelium and the invasion of some neoplastic masses, was greatly reduced in the LipoNio.BR group compared to the FBR-(free berberine) administrated group. Following CRC induction, immunohistochemical staining revealed that the overexpression of cyclin and COX-2 in colonic tissues were suppressed in the LipoNio.BR group. Taken together, these findings suggest that LipoNio.BR has a potential role in reducing CRC progression to a greater extent compared to free BR and could be considered a promising and potent therapy against CRC.
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Affiliation(s)
- Doaa Ibrahim
- Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt.
| | - Safaa I Khater
- Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University, 44519 Zagazig, Egypt.
| | - Ahmed Abdelfattah-Hassan
- Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt; Biomedical Sciences Program, University of Science and Technology, Zewail City of Science and Technology, October Gardens, 6th of October, Giza 12578, Egypt.
| | - Leena S Alqahtani
- Department of Biochemistry, College of Science, University of Jeddah, Jeddah 80203, Saudi Arabia.
| | - Aya Sh Metwally
- Department of Pharmacology, Factulty of Vet. Medicine, Aswan University, Egypt.
| | - Shefaa M Bazeed
- Department of Biochemistry and Animal Physiology, Faculty of Veterinary Medicine, Badr University in Cairo (BUC), Cairo, Egypt.
| | - Aya Elgamal
- Department of Animal Histology and Anatomy, Faculty of Veterinary Medicine, Badr University in Cairo (BUC), Cairo, Egypt.
| | - Nagwa I Sheraiba
- Department of Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, University of Sadat City, Sadat 32897, Egypt.
| | - Elham M Hussein
- Physics Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt.
| | - Fatmah Ali Alasmary
- Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
| | - Gamal A Salem
- Department of Pharmacology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt.
| | - Mohamed Ali
- Department of Biochemistry, Faculty of Science, Zagazig University, 44519 Zagazig, Egypt.
| | - Hala Mahfouz
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
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Mouliou DS. C-Reactive Protein: Pathophysiology, Diagnosis, False Test Results and a Novel Diagnostic Algorithm for Clinicians. Diseases 2023; 11:132. [PMID: 37873776 PMCID: PMC10594506 DOI: 10.3390/diseases11040132] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 09/15/2023] [Accepted: 09/19/2023] [Indexed: 10/25/2023] Open
Abstract
The current literature provides a body of evidence on C-Reactive Protein (CRP) and its potential role in inflammation. However, most pieces of evidence are sparse and controversial. This critical state-of-the-art monography provides all the crucial data on the potential biochemical properties of the protein, along with further evidence on its potential pathobiology, both for its pentameric and monomeric forms, including information for its ligands as well as the possible function of autoantibodies against the protein. Furthermore, the current evidence on its potential utility as a biomarker of various diseases is presented, of all cardiovascular, respiratory, hepatobiliary, gastrointestinal, pancreatic, renal, gynecological, andrological, dental, oral, otorhinolaryngological, ophthalmological, dermatological, musculoskeletal, neurological, mental, splenic, thyroid conditions, as well as infections, autoimmune-supposed conditions and neoplasms, including other possible factors that have been linked with elevated concentrations of that protein. Moreover, data on molecular diagnostics on CRP are discussed, and possible etiologies of false test results are highlighted. Additionally, this review evaluates all current pieces of evidence on CRP and systemic inflammation, and highlights future goals. Finally, a novel diagnostic algorithm to carefully assess the CRP level for a precise diagnosis of a medical condition is illustrated.
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Jiang H, Zhou S, Li G. Novel biomarkers used for early diagnosis and tyrosine kinase inhibitors as targeted therapies in colorectal cancer. Front Pharmacol 2023; 14:1189799. [PMID: 37719843 PMCID: PMC10502318 DOI: 10.3389/fphar.2023.1189799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 08/14/2023] [Indexed: 09/19/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common and second most lethal type of cancer worldwide, presenting major health risks as well as economic costs to both people and society. CRC survival chances are significantly higher if the cancer is diagnosed and treated early. With the development of molecular biology, numerous initiatives have been undertaken to identify novel biomarkers for the early diagnosis of CRC. Pathological disorders can be diagnosed at a lower cost with the help of biomarkers, which can be detected in stool, blood, and tissue samples. Several lines of evidence suggest that the gut microbiota could be used as a biomarker for CRC screening and treatment. CRC treatment choices include surgical resection, chemotherapy, immunotherapy, gene therapy, and combination therapies. Targeted therapies are a relatively new and promising modality of treatment that has been shown to increase patients' overall survival (OS) rates and can inhibit cancer cell development. Several small-molecule tyrosine kinase inhibitors (TKIs) are being investigated as potential treatments due to our increasing awareness of CRC's molecular causes and oncogenic signaling. These compounds may inhibit critical enzymes in controlling signaling pathways, which are crucial for CRC cells' development, differentiation, proliferation, and survival. On the other hand, only one of the approximately 42 TKIs that demonstrated anti-tumor effects in pre-clinical studies has been licensed for clinical usage in CRC. A significant knowledge gap exists when bringing these tailored medicines into the clinic. As a result, the emphasis of this review is placed on recently discovered biomarkers for early diagnosis as well as tyrosine kinase inhibitors as possible therapy options for CRC.
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Abraham AT, Padam S. Clostridium septicum Bacteremia As the Presenting Sign of Colon Cancer. Cureus 2023; 15:e45343. [PMID: 37849577 PMCID: PMC10577671 DOI: 10.7759/cureus.45343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/15/2023] [Indexed: 10/19/2023] Open
Abstract
Colon cancer is one of the leading causes of morbidity and mortality throughout the world. Some of the most common presenting signs are a change in bowel habits, alteration of fecal contour or consistency, blood in stool, fatigue, and weight loss. However, it may present insidiously. This is the case of an 81-year-old female with Clostridium septicum bacteremia as the primary presenting sign of metastatic colon cancer. In further literature review, we discuss the genomic associations that contribute to the severity of the disease and explore the potential links between the gut microbiome and colorectal carcinoma. This article highlights risk factor modifications and lab abnormalities that may be useful for the primary care provider and acute care practitioner.
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Affiliation(s)
- Andrew T Abraham
- Internal Medicine, University of Central Florida College of Medicine, Graduate Medical Education/Hospital Corporation of America (HCA) Florida, North Florida Hospital, Gainesville, USA
| | - Sripal Padam
- Internal Medicine, University of Central Florida College of Medicine, Graduate Medical Education/Hospital Corporation of America (HCA) Florida, North Florida Hospital, Gainesville, USA
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Malkani N, Rashid MU. Systemic Diseases and Gastrointestinal Cancer Risk. JOURNAL OF CANCER & ALLIED SPECIALTIES 2023; 9:473. [PMID: 37575213 PMCID: PMC10405983 DOI: 10.37029/jcas.v9i2.473] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 06/15/2023] [Indexed: 08/15/2023]
Abstract
Importance Gastrointestinal (GI) cancers are the second leading cause of cancer-related deaths worldwide. Observations The global challenges GI cancers pose are high, especially in middle- and low-income countries. Patients with these cancers present with symptoms of poor appetite, weight loss, heartburn, abdominal pain, fatigue and anaemia. Several risk factors contribute to GI cancers, including age, gender, obesity, pathogenic infections, smoking cigarettes, alcohol consumption and dietary habits. Most of these cancers are sporadic. However, some patients are at high risk due to a family history of GI cancers. Systemic diseases affect multiple organs, and their chronic occurrence elicits inflammatory responses at various sites. These diseases also contribute to GI cancers. Conclusion and Relevance In this review, we discuss that untreated systemic diseases, including diabetes, hepatitis, acquired immune deficiency syndrome, ulcers and hypertension, can potentially lead to GI cancers if they remain untreated for a longer period. Systemic diseases initiate oxidative stress, inflammatory pathways and genetic manipulations, which altogether confer risks to GI cancers. Here, we describe the association between systemic diseases and their underlying mechanisms leading to GI cancers.
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Affiliation(s)
- Naila Malkani
- Department of Zoology, Government College University, Lahore, Punjab, Pakistan
| | - Muhammad Usman Rashid
- Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan
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Luo Y, Yuan H, Pei Q, Chen Y, Xian J, Du R, Ye T. Artificial neural network-based diagnostic models for lung cancer combining conventional indicators with tumor markers. Exp Biol Med (Maywood) 2023; 248:829-838. [PMID: 37403334 PMCID: PMC10484194 DOI: 10.1177/15353702231177013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 03/16/2023] [Indexed: 07/06/2023] Open
Abstract
This study set out to establish a lung cancer diagnosis and prediction model uses conventional laboratory indicators combined with tumor markers, so as to help early screening and auxiliary diagnosis of lung cancer through a convenient, fast, and cheap way, and improve the early diagnosis rate of lung cancer. A total of 221 patients with lung cancer, 100 patients with benign pulmonary diseases, and 184 healthy subjects were retrospectively studied. General clinical data, the results of conventional laboratory indicators, and tumor markers were collected. Statistical Product and Service Solutions 26.0 was used for data analysis. The diagnosis and prediction model of lung cancer was established by artificial neural network - multilayer perceptron. After correlation and difference analysis, five comparison groups (lung cancer-benign lung disease group, lung cancer-health group, benign lung disease-health group, early-stage lung cancer-benign lung disease group, and early-stage lung cancer-health group) obtained 5, 28, 25, 16, and 25 valuable indicators for predicting lung cancer or benign lung disease, and then established five diagnostic prediction models, respectively. The area under the curve (AUC) of each combined diagnostic prediction model (0.848, 0.989, 0.949, 0.841, and 0.976) was higher than that of the diagnostic prediction model established only using tumor markers (0.799, 0.941, 0.830, 0.661, and 0.850), and the difference in the lung cancer-health group, the benign lung disease-health group, the early-stage lung cancer-benign lung disease group, and early-stage lung cancer-health group was statistically significant (P < 0.05). The artificial neural network-based diagnostic models for lung cancer combining conventional indicators with tumor markers have high performance and clinical significance in assisting the diagnosis of early lung cancer.
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Affiliation(s)
- Yanan Luo
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, P.R. China
| | - Hui Yuan
- Department of Pathophysiology, Mudanjiang Medical University, Mudanjiang 157011, P.R. China
| | - Qin Pei
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, P.R. China
| | - Yiyu Chen
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, P.R. China
| | - Jiawen Xian
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, P.R. China
| | - Rongrong Du
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, P.R. China
| | - Ting Ye
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, P.R. China
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Jiang W, Ma Z, Cao F, Hu L, Bao L, Chang P, Xu C, Lv X, Xie Y. Label-free integrated microfluidic plasmonic biosensor from vertical-cavity surface-emitting lasers for SARS-CoV-2 receptor binding domain protein detection. OPTICS EXPRESS 2023; 31:12138-12149. [PMID: 37157379 DOI: 10.1364/oe.486605] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
The nanoplasmonic sensor of the nanograting array has a remarkable ability in label-free and rapid biological detection. The integration of the nanograting array with the standard vertical-cavity surface-emitting lasers (VCSEL) platform can achieve a compact and powerful solution to provide on-chip light sources for biosensing applications. Here, a high sensitivity and label-free integrated VCSELs sensor was developed as a suitable analysis technique for COVID-19 specific receptor binding domain (RBD) protein. The gold nanograting array is integrated on VCSELs to realize the integrated microfluidic plasmonic biosensor of on-chip biosensing. The 850 nm VCSELs are used as a light source to excite the localized surface plasmon resonance (LSPR) effect of the gold nanograting array to detect the concentration of attachments. The refractive index sensitivity of the sensor is 2.99 × 106 nW/RIU. The aptamer of RBD was modified on the surface of the gold nanograting to detect the RBD protein successfully. The biosensor has high sensitivity and a wide detection range of 0.50 ng/mL - 50 µg/mL. This VCSELs biosensor provides an integrated, portable, and miniaturized idea for biomarker detection.
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Zhang Y, Yang Y, Zan L, Wang J, Yan L, Zhao L, Chen L, Xi Y, Bai W, Yang X. Preparation and application of patient-derived xenograft mice model of colorectal cancer. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2023; 26:248-254. [PMID: 36742145 PMCID: PMC9869887 DOI: 10.22038/ijbms.2022.67445.14780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 11/16/2022] [Indexed: 02/07/2023]
Abstract
Objectives Patient-derived xenograft (PDX) model becomes a more and more important tool for tumor research. This study aimed to establish a colorectal cancer PDX model and verify its applicability. Materials and Methods Fresh human colorectal cancer tissue was surgically removed and subcutaneously inoculated into immunodeficient mice to establish the PDX model. Hematoxylin and eosin (HE) staining and immunohistochemical staining were used to evaluate the model. The successful PDX model was selected to study the efficacy of capecitabine in treating colorectal cancer. Results HE staining showed that the PDX mice model of colorectal cancer could preserve the histological characteristics of the primary tumor. Immunohistochemistry staining showed α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and E-cadherin were strongly positively expressed in primary human and PDX tumor tissues, with a high degree of similarity. Capecitabine significantly inhibited PDX tumor growth and reduced the expression of AFP and CEA proteins in the tumor tissues (all P s<0.05). Conclusion We successfully established a colorectal cancer PDX model, and the PDX model could retain the histological and biological characteristics of the primary tumor. Using this PDX model, we revealed that capecitabine at a dose of 300-400 mg/kg can effectively treat colorectal cancer, and no significant difference in toxicity was found among different dose groups. The current work provides a feasible framework for establishing and validating the PDX tumor model to better facilitate the evaluation of drug efficacy and safety.
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Affiliation(s)
- Yutao Zhang
- Department of Colorectal and Anal Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China,These authors contributed eqully to this work
| | - Yongming Yang
- Laboratory Animal Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China,These authors contributed eqully to this work
| | - Likun Zan
- Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China
| | - Jing Wang
- Laboratory Animal Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China
| | - Lei Yan
- Laboratory Animal Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China
| | - Lili Zhao
- Laboratory Animal Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China
| | - Lixia Chen
- Laboratory Animal Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China
| | - Yanfeng Xi
- Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China,Corresponding authors: Yanfeng Xi. Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China. ; Wenqi Bai. Department of Colorectal and Anal Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China. ; Xihua Yang. Laboratory Animal Cente, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China. Tel: 86+13403419805;
| | - Wenqi Bai
- Department of Colorectal and Anal Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China,Corresponding authors: Yanfeng Xi. Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China. ; Wenqi Bai. Department of Colorectal and Anal Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China. ; Xihua Yang. Laboratory Animal Cente, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China. Tel: 86+13403419805;
| | - Xihua Yang
- Laboratory Animal Center, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China,Corresponding authors: Yanfeng Xi. Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China. ; Wenqi Bai. Department of Colorectal and Anal Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China. ; Xihua Yang. Laboratory Animal Cente, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, 030013, Taiyuan, Shanxi, China. Tel: 86+13403419805;
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Abo-elela DA, Salem AMH, Swellam M, Hegazy MGA. Potential diagnostic role of circulating MiRNAs in colorectal cancer. Int J Immunopathol Pharmacol 2023; 37:3946320221144565. [PMID: 36598779 PMCID: PMC9830083 DOI: 10.1177/03946320221144565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
OBJECTIVES Colorectal cancer (CRC) is the third most common and fourth most deadly cancer worldwide despite its various screening method. Thus, the search for novel and better markers is continuous. This study aimed to assess the combined expression levels of miR-133a, miR-574-3p, and miR-27a in early diagnosis of colorectal cancer in comparison to traditional tumor markers (CEA and CA19.9). METHODS miR-133a, miR-574-3p, and miR-27a were assessed in sera of 120 participants categorized into healthy control group (n = 20), benign group (n = 30) and malignant group (n = 70) using real-time PCR. RESULTS miR-133a, miR-574-3p, and miR-27a expressions showed significant difference among different staging, grading and tumor size of CRC. The sensitivities of the three miRNAs whether combined or individually used were better than routinely used tumor markers (CEA and CA19.9) leading to more accurate and faster diagnosis of CRC. CONCLUSION Synergetic detection of miRNA-133a, miRNA-574-3p, and miRNA-27a may serve as better noninvasive biomarkers with higher combined sensitivity for early diagnosis of CRC than individual detection of miRNAs.
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Affiliation(s)
- Dina A Abo-elela
- Biochemistry Department, Faculty of
Science, Ain Shams
University, Cairo, Egypt
| | - Ahmed MH Salem
- Biochemistry Department, Faculty of
Science, Ain Shams
University, Cairo, Egypt
| | - Menha Swellam
- Biochemistry Department,
Biotechnology Research Institute, High Throughput Molecular and Genetic
laboratory, Central Laboratories Network and the Centers of Excellence,
National
Research Centre, Cairo, Egypt
| | - Marwa GA Hegazy
- Biochemistry Department, Faculty of
Science, Ain Shams
University, Cairo, Egypt
- Marwa GA Hegazy, Department of
Biochemistry, Faculty of science, Ain Shams University, Abassia, Cairo 11566,
Egypt. ;
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Gegovska M, Hiljadnikova-Bajro M. Novel laboratory biomarkers in colorectal cancer management. MAKEDONSKO FARMACEVTSKI BILTEN 2022. [DOI: 10.33320/maced.pharm.bull.2022.68.03.160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Affiliation(s)
- Marija Gegovska
- Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Mother Theresa 47, 1000 Skopje, Republic of North Macedonia
| | - Marija Hiljadnikova-Bajro
- Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Mother Theresa 47, 1000 Skopje, Republic of North Macedonia
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Cancer secretome: finding out hidden messages in extracellular secretions. Clin Transl Oncol 2022; 25:1145-1155. [PMID: 36525229 DOI: 10.1007/s12094-022-03027-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/23/2022] [Indexed: 12/23/2022]
Abstract
Secretome analysis has gained popularity recently as a very well-designed proteomic approach that is being used to study various interactions and their effects on cellular activity. This analysis is especially helpful while studying the effects of the cells on their microenvironment, paracrine and autocrine processes, their therapeutic purposes, and as a new diagnostic perspective. Cancer is a condition rather than a specific type of disease and is still yet to be fully understood. Cancer secretome is a fairly new concept that is being implemented to examine the interactions taking place in the tumor microenvironment and can help to understand the phenomena like induction of tumorigenesis, stimulation of immune cells, etc. The secretome analysis helps to gain a different perspective on the existing knowledge on cancer and its effects. The recent advances in secretome studies are directed toward secreted components as drug targets, biomarkers, and companion tools for diagnostic and prognostic purposes in cancer. This review aims to find the interactors in different types of cancer and understand the existing unstructured secretome data and its application in prognosis, diagnosis, and in biomarker study.
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Yi X, Hu W. Advances in adoptive cellular therapy for colorectal cancer: a narrative review. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:1404. [PMID: 36660664 PMCID: PMC9843349 DOI: 10.21037/atm-22-6196] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 12/19/2022] [Indexed: 01/01/2023]
Abstract
Background and Objective In recent years, adoptive cell therapy (ACT) has shown great potential in antitumor treatment. To significantly improve the clinical efficacy of ACT against solid tumors, we may need to carefully study the latest developments in ACT. As one of the most common malignancies, colorectal cancer (CRC) is a major risk to human health and has become a significant burden on global healthcare systems. This article reviews the recent advances in the treatment of CRC with ACT. Methods We searched PubMed for articles related to ACT for CRC published as of August 31, 2022, and retrieved relevant clinical trial information on the National Institutes of Health ClinicalTrials.gov website. Based on search results, comprehensive and systematic review is made. Key Content and Findings This article provides an overview of the research progress of ACT for CRC, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR)-engineered T-cell therapy, and tumor-infiltrating lymphocyte (TIL) therapy. Common tumor-associated antigens (TAAs) in clinical trials of CAR-T cell therapy for CRC are described. Conclusions Despite many obstacles, ACT shows great promise in treating CRC. Therefore, more basic experimental studies and clinical trials are warranted to further clarify the effectiveness and safety of ACT.
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Affiliation(s)
- Xing Yi
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Wenwei Hu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China
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Jia SN, Han YB, Yang R, Yang ZC. Chemokines in colon cancer progression. Semin Cancer Biol 2022; 86:400-407. [PMID: 35183412 DOI: 10.1016/j.semcancer.2022.02.007] [Citation(s) in RCA: 73] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/02/2022] [Accepted: 02/03/2022] [Indexed: 01/27/2023]
Abstract
Colon cancer is a major human cancer accounting for about a tenth of all cancer cases thus making it among the top three cancers in terms of incidence as well as mortality. Metastasis to distant organs, particularly to liver, is the primary reason for associated mortality. Chemokines, the chemo-attractants for various immune cells, have increasingly been reported to be involved in cancer initiation and progression, including in colon cancer. Here we discuss the available knowledge on the role of several chemokines, such as, CCL2, CCL3, CCL5, CXCL1, CXCL2, CXCL8 in colon cancer progression. CCL20 is one chemokine with emerging evidence for its role in influencing colon cancer tumor microenvironment through the documents effects on fibroblasts, macrophages and immune cells. We focus on CCL20 and its receptor CCR6 as promising factors that affect multiple levels of colon cancer progression. They interact with several cytokines and TLR receptors leading to increased aggressiveness, as supported by multitude of evidence from in vitro, in vivo studies as well as human patient samples. CCL20-CCR6 bring about their biological effects through regulation of several signaling pathways, including, ERK and NF-κB pathways, in addition to the epithelial-mesenchymal transition. Signaling involving CCL20-CCR6 has profound effect on colon cancer hepatic metastasis. Combined with elevated CCL20 levels in colon tumors and metastatic patients, the above information points to a need for further evaluation of chemokines as diagnostic and/or prognostic biomarkers.
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Affiliation(s)
- Sheng-Nan Jia
- Department of HepatoPancreatoBiliary Medicine, The Second Hospital of Jilin University, Changchun, 130000, China
| | - Ying-Bo Han
- Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, 130000, China
| | - Rui Yang
- Department of Gastroenterology, The Second Hospital of Jilin University, Changchun, 130000, China
| | - Ze-Cheng Yang
- Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, 130000, China.
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Qin X, Wu F, Chen C, Li Q. Recent advances in CAR-T cells therapy for colorectal cancer. Front Immunol 2022; 13:904137. [PMID: 36238297 PMCID: PMC9551069 DOI: 10.3389/fimmu.2022.904137] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 09/09/2022] [Indexed: 11/17/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer, with a high mortality rate and a serious impact on people’s life and health. In recent years, adoptive chimeric antigen receptor T (CAR-T) cells therapy has shown well efficacy in the treatment of hematological malignancies, but there are still many problems and challenges in solid tumors such as CRC. For example, the tumor immunosuppressive microenvironment, the low targeting of CAR-T cells, the short time of CAR-T cells in vivo, and the limited proliferation capacity of CAR-T cells, CAR-T cells can not effectively infiltrate into the tumor and so on. New approaches have been proposed to address these challenges in CRC, and this review provides a comprehensive overview of the current state of CAR-T cells therapy in CRC.
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Affiliation(s)
- Xiaoling Qin
- Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Fengjiao Wu
- Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Chang Chen
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Department of Pharmacology, Harbin Medical University, Harbin, China
- *Correspondence: Qi Li, ; Chang Chen,
| | - Qi Li
- Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin, China
- *Correspondence: Qi Li, ; Chang Chen,
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Yin H, Huang Z, Niu S, Ming L, Jiang H, Gu L, Huang W, Xie J, He Y, Zhang C. 5-Methylcytosine (m5C) modification in peripheral blood immune cells is a novel non-invasive biomarker for colorectal cancer diagnosis. Front Immunol 2022; 13:967921. [PMID: 36211353 PMCID: PMC9532581 DOI: 10.3389/fimmu.2022.967921] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 09/02/2022] [Indexed: 11/23/2022] Open
Abstract
Current non-invasive tumor biomarkers failed to accurately identify patients with colorectal cancer (CRC), delaying CRC diagnosis and thus leading to poor prognosis. Dysregulation of 5-Methylcytosine (m5C) RNA has gradually been reported in various cancers, but their role in tumor diagnosis is rarely mentioned. Our study aimed to determine the role of m5C methylation modification in blood immune cells for the diagnosis of CRC. Peripheral blood samples were obtained from a total of 83 healthy controls and 196 CRC patients. We observed that m5C RNA contents in blood immune cells of CRC patients were markedly enhanced in both training set and validation set. Moreover, levels of m5C increased with CRC progression and metastasis but reduced after treatment. Compared with common blood tumor biomarkers, m5C levels in peripheral blood immune cells had superior discrimination and reclassification performance in diagnosing CRC. Besides, bioinformatics and qRT-PCR analysis identified increased expression of m5C-modified regulators NSUN5 and YBX1 in CRC patients’ blood. A series of animal models and cell co-culture models further demonstrated that CRC tumor cells could increase immune cells’ m5C levels and m5C-modified regulators. Monocyte was the predominant m5C-modified immune cell type in CRC patients’ blood by Gene set variation analysis (GSVA). Taken together, m5C methylation modification in peripheral blood immune cells was a promising biomarker for non-invasive diagnosis of CRC.
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Affiliation(s)
- Haofan Yin
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Zhijian Huang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Shiqiong Niu
- Department of Clinical Laboratory, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Liang Ming
- Department of Clinical Laboratory, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Hongbo Jiang
- Department of Clinical Laboratory, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Liang Gu
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Weibin Huang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
| | - Jinye Xie
- Department of Clinical Laboratory, Zhongshan City People's Hospital, The Affiliated Zhongshan Hospital of Sun Yat-Sen University, Zhongshan, China
- *Correspondence: Changhua Zhang, ; Yulong He, ; Jinye Xie,
| | - Yulong He
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
- *Correspondence: Changhua Zhang, ; Yulong He, ; Jinye Xie,
| | - Changhua Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
- Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China
- *Correspondence: Changhua Zhang, ; Yulong He, ; Jinye Xie,
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Demiryas S, Orhan A. Advancements in Gastrointestinal System Biomarkers. Biomark Med 2022. [DOI: 10.2174/9789815040463122010016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The requirement for diagnostic surgical operations of gastrointestinal system
diseases significantly decreases with the help of proper diagnostic tools. These
modalities are also beneficial for identifying postoperative complications, allowing us
to diagnose them in earlier stages, and increasing the postoperative survival rates.
Biomarkers are considered an integral part of diagnostic examinations. Developments
of biomarkers used for diagnosing and treating abdominal diseases are essential for
improving our capabilities in non-invasive monitoring. In this chapter, we review both
the novel and the routine biomarkers in the diagnosis and follow-up of gastrointestinal
system diseases.
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Affiliation(s)
- Suleyman Demiryas
- Department of General Surgery, Cerrahpaşa School of Medicine, IIstanbul University –
Cerrahpaşa, Istanbul, Turkey
| | - Anıl Orhan
- Department of General Surgery, Haseki Training and Research Hospital, University of Health
Sciences, Istanbul, Turkey
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Modulating the Siah2-PHD3-HIF1α axis and/or autophagy potentially retard colon cancer proliferation possibly, due to the damping of colon cancer stem cells. Biomed Pharmacother 2022; 154:113562. [PMID: 35994813 DOI: 10.1016/j.biopha.2022.113562] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 08/11/2022] [Accepted: 08/14/2022] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Hypoxic microenvironment of colon cancer is associated with HIF-1α upregulation. HIF-1α response elements are responsible for autophagy induction that promotes tumor proliferation. Moreover, HIF-1α induces tumor cell proliferation via maintaining cancer stem cells (CSCs) survival. Siah2 is E3 ubiquitin ligase that indirectly stabilizes HIF-1α. We hypothesized that dual inhibition of Siah2 as well as autophagy could be a promising approach that may inhibit CSCs growth. AIM OF THE WORK This study investigated the possible effect of vitamin K3 as a Siah2 inhibitor and hydroxychloroquine as an autophagy inhibitor in colon cancer management. The effect (if any) of these agents on CSCs growth will be also manipulated. METHODS Colon cancer was induced by dimethylhydrazine. MDA and GSH were selected as oxidative stress markers, Expression of HIF-1α, Caspase-3, VEGF, MMP-9, EpCAM, SCF, and CA19.9 were assayed using immunoassay. The Western blot technique was used to assess LC3Ⅰ, CD44, and CD133 whereas RT-PCR was used to investigate PHD3 and CD44 in colon tissues. Additionally, Ki-67 and Siah2 were detected immunohistochemically. RESULTS vitamin K3 and hydroxychloroquine either alone or in combination downregulated the expression of Siah2 and HIF-1α through upregulating PHD3 in colon tissues. This combination significantly downregulated MDA, Ki-67, VEGF, and MMP-9 expression and upregulated the expression of GSH and caspase-3. LC3Ⅰ was also upregulated. Interestingly, these therapeutic options were correlated with down-regulation of the cancer stem cell marker such as CD44 and EpCAM. CONCLUSION Our results suggested that suppression of both Siah2-PHD3-HIF-1α axis and autophagy retard colon cancer proliferation and dampened CSCs.
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Gattuso G, Crimi S, Lavoro A, Rizzo R, Musumarra G, Gallo S, Facciponte F, Paratore S, Russo A, Bordonaro R, Isola G, Bianchi A, Libra M, Falzone L. Liquid Biopsy and Circulating Biomarkers for the Diagnosis of Precancerous and Cancerous Oral Lesions. Noncoding RNA 2022; 8:60. [PMID: 36005828 PMCID: PMC9414906 DOI: 10.3390/ncrna8040060] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/21/2022] [Accepted: 08/08/2022] [Indexed: 12/19/2022] Open
Abstract
Oral cancer is one of the most common malignancies worldwide, accounting for 2% of all cases annually and 1.8% of all cancer deaths. To date, tissue biopsy and histopathological analyses are the gold standard methods for the diagnosis of oral cancers. However, oral cancer is generally diagnosed at advanced stages with a consequent poor 5-year survival (~50%) due to limited screening programs and inefficient physical examination strategies. To address these limitations, liquid biopsy is recently emerging as a novel minimally invasive tool for the early identification of tumors as well as for the evaluation of tumor heterogeneity and prognosis of patients. Several studies have demonstrated that liquid biopsy in oral cancer could be useful for the detection of circulating biomarkers including circulating tumor DNA (ctDNA), microRNAs (miRNAs), proteins, and exosomes, thus improving diagnostic strategies and paving the way to personalized medicine. However, the application of liquid biopsy in oral cancer is still limited and further studies are needed to better clarify its clinical impact. The present manuscript aims to provide an updated overview of the potential use of liquid biopsy as an additional tool for the management of oral lesions by describing the available methodologies and the most promising biomarkers.
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Affiliation(s)
- Giuseppe Gattuso
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Salvatore Crimi
- Department of General Surgery and Medical Surgery Specialties, University of Catania, 95123 Catania, Italy
| | - Alessandro Lavoro
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Roberta Rizzo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Giorgia Musumarra
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Simona Gallo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Flavia Facciponte
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | | | - Angela Russo
- Medical Oncology Unit, ARNAS Garibaldi, 95122 Catania, Italy
| | | | - Gaetano Isola
- Department of General Surgery and Surgical-Medical Specialties, School of Dentistry, University of Catania, Via S. Sofia 78, 95124 Catania, Italy
| | - Alberto Bianchi
- Department of General Surgery and Medical Surgery Specialties, University of Catania, 95123 Catania, Italy
| | - Massimo Libra
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
- Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123 Catania, Italy
| | - Luca Falzone
- Epidemiology and Biostatistics Unit, IRCCS Istituto Nazionale Tumori “Fondazione G. Pascale”, 80131 Naples, Italy
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Lindgren M, Rask G, Jonsson J, Berglund A, Lundin C, Jonsson P, Ljuslinder I, Nyström H. Type IV Collagen in Human Colorectal Liver Metastases—Cellular Origin and a Circulating Biomarker. Cancers (Basel) 2022; 14:cancers14143396. [PMID: 35884455 PMCID: PMC9325127 DOI: 10.3390/cancers14143396] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/30/2022] [Accepted: 07/11/2022] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Patients with colorectal liver metastases (CLM) can be cured through surgery if metastases are detected early in disease progression. Today, CLM diagnosis relies heavily on diagnostic imaging, and cheap, non-invasive, and efficiently measurable biomarkers are needed. Circulating type IV collagen (COL IV) is a potential biomarker for detecting CLM. Patients with CLM show elevated circulating levels of COL IV and increased tissue expression of COL IV in CLM tissue, which could result from enhanced production and degradation of COL IV. This study aimed to establish the cellular source behind enhanced COL IV levels, which is helpful in the evaluation of the biomarker potential of COL IV. We show that fibroblasts express COL IV both in vitro and in the stromal tissue of CLM. We also found that CLM tissue expresses COL IV-degrading proteases. Lastly, CLM patients have higher circulating COL IV levels than healthy controls. Abstract Circulating type IV collagen (cCOL IV) is a potential biomarker for patients with colorectal liver metastases (CLM) who present with elevated levels of COL IV in both CLM tissue and circulation. This study aimed to establish the cellular origin of elevated levels of COL IV and analyze circulating COL IV in CLM patients. The cellular source was established through in situ hybridization, immunohistochemical staining, and morphological evaluation. Cellular expression in vitro was assessed by immunofluorescence. Tissue expression of COL IV-degrading matrix metalloproteinases (MMPs)-2, -7, -9, and -13 was studied with immunohistochemical staining. Plasma levels of COL IV in CLM patients and healthy controls were analyzed with ELISA. This study shows that cancer-associated fibroblasts (CAFs) express COL IV in the stroma of CLM and that COL IV is expressed in vitro by fibroblasts but not by tumor cells. MMP-2, -7, -9, and -13 are expressed in CLM tissue, mainly by hepatocytes and immune cells, and circulating COL IV is significantly elevated in CLM patients compared with healthy controls. Our study shows that stromal cells, not tumor cells, produce COL IV in CLM, and that circulating COL IV is elevated in patients with CLM.
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Affiliation(s)
- Moa Lindgren
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
- Correspondence:
| | - Gunilla Rask
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
- Department of Medical Biosciences/Pathology, Umeå University, SE-901 87 Umeå, Sweden
| | - Josefin Jonsson
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
| | - Anette Berglund
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
| | - Christina Lundin
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
| | - Pär Jonsson
- Department of Chemistry, Umeå University, SE-907 36 Umeå, Sweden;
| | - Ingrid Ljuslinder
- Department of Radiation Sciences/Oncology, Umeå University, SE-901 87 Umeå, Sweden;
| | - Hanna Nyström
- Department of Surgical and Perioperative Sciences/Surgery, Umeå University, SE-901 85 Umeå, Sweden; (G.R.); (J.J.); (A.B.); (C.L.); (H.N.)
- Wallenberg Centre for Molecular Medicine, Umeå University, SE-901 87 Umeå, Sweden
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Inhibition of NLRP3 by Fermented Quercetin Decreases Resistin-Induced Chemoresistance to 5-Fluorouracil in Human Colorectal Cancer Cells. Pharmaceuticals (Basel) 2022; 15:ph15070798. [PMID: 35890097 PMCID: PMC9324057 DOI: 10.3390/ph15070798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 06/16/2022] [Accepted: 06/21/2022] [Indexed: 02/07/2023] Open
Abstract
The drug resistance of colorectal cancer (CRC) cells against 5-fluorouracil (5-FU) therapy is a major challenge to successful cancer treatment. While previous studies have proposed several 5-FU resistance mechanisms, the effects of the adipokines on cancer cells remain unclear. Thus, this study investigated the effect of resistin on 5-FU-treated CRC cell lines. The upregulation of NLRP3 can regulate the inflammatory responses in cancer cells and then enhance cancer progression. This study investigated the expression level and the function of NLRP3 on 5-FU-induced cytotoxicity in CRC cells and found that resistin-induced ERK activation and increased NLRP3 expression in CRC HCT-116 and DLD-1 cells were mediated by Toll-like receptor 4 (TLR4). The inhibition of TLR4 and ERK by pharmacological inhibitors attenuated the resistin-induced NLRP3 mRNA and protein levels. In contrast, the knockdown of NLRP3 enhanced the cytotoxic effects of 5-FU. Furthermore, quercetin is an effective chemopreventive compound. This study showed that quercetin fermented by Lactobacillus could exhibit low cytotoxicity on normal mucosa cells and improve the function of inhibiting CRC cells. The treatment of CRC cells with fermented quercetin increased the cytotoxicity and enhanced cell death in the presence of resistin. In this study, fermented quercetin induced the cytotoxicity and cell death of 5-FU in resistin-treated CRC cells, which is associated with the downregulation of NLRP3 expression and ERK phosphorylation. These results indicate the role of NLRP3 in the development of drug resistance to 5-FU in CRC cells. Elucidating the mechanism regarding the cytotoxicity effect of quercetin may provide another vision for the development of a chemotherapy strategy for CRC in the future.
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Karthika C, Sureshkumar R, Zehravi M, Akter R, Ali F, Ramproshad S, Mondal B, Kundu MK, Dey A, Rahman MH, Antonescu A, Cavalu S. Multidrug Resistance in Cancer Cells: Focus on a Possible Strategy Plan to Address Colon Carcinoma Cells. Life (Basel) 2022; 12:811. [PMID: 35743842 PMCID: PMC9224881 DOI: 10.3390/life12060811] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 05/26/2022] [Indexed: 12/20/2022] Open
Abstract
Even though various treatment methods are available for cancer, the death curve is not reducing. The diagnosis of cancer at the fourth stage and drug resistance are the leading reasons for treatment failure and lower survival rates. In this review article, we summarize the possible pitfalls during cancer treatment in general, which mainly include multidrug resistance, and propose a hypothesis for colorectal cancer specifically. We also evaluate multidrug resistance in cancer in general and colorectal cancer in particular and hypothesize a concept based on combination therapy with 5-fluorouracil, curcumin, and lipids for the possible management of colorectal cancer. In addition, a hypothetical approach, combining a synthetic agent and a natural chemotherapeutic agent, to treating colorectal cancer is also discussed. This hypothesis could improve the management of colorectal cancer.
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Affiliation(s)
- Chenmala Karthika
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty 643001, India;
| | - Raman Sureshkumar
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty 643001, India;
| | - Mehrukh Zehravi
- Department of Clinical Pharmacy Girls Section, Prince Sattam Bin Abdul Aziz University, Alkharj 11942, Saudi Arabia;
| | - Rokeya Akter
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, 24, Wonju 26426, Korea;
| | - Faraat Ali
- Department of Licensing and Enforcement, Laboratory Services, Botswana Medicines Regulatory Authority (BoMRA), Gaborone 999106, Botswana;
| | - Sarker Ramproshad
- Department of Pharmacy, Ranada Prasad Shaha University, Narayanganj 1400, Bangladesh; (S.R.); (B.M.)
| | - Banani Mondal
- Department of Pharmacy, Ranada Prasad Shaha University, Narayanganj 1400, Bangladesh; (S.R.); (B.M.)
| | | | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata 700073, India;
| | - Md. Habibur Rahman
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, 24, Wonju 26426, Korea;
| | - Angela Antonescu
- Faculty of Medicine and Pharmacy, University of Oradea, Pta 1 Decembrie 10, 410087 Oradea, Romania;
| | - Simona Cavalu
- Faculty of Medicine and Pharmacy, University of Oradea, Pta 1 Decembrie 10, 410087 Oradea, Romania;
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Sena P, Mancini S, Pedroni M, Reggiani Bonetti L, Carnevale G, Roncucci L. Expression of Autophagic and Inflammatory Markers in Normal Mucosa of Individuals with Colorectal Adenomas: A Cross Sectional Study among Italian Outpatients Undergoing Colonoscopy. Int J Mol Sci 2022; 23:5211. [PMID: 35563601 PMCID: PMC9104783 DOI: 10.3390/ijms23095211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 04/29/2022] [Accepted: 05/05/2022] [Indexed: 02/04/2023] Open
Abstract
Colorectal cancer (CRC) ranks among the three most common cancers in terms of both cancer incidence and cancer-related deaths in Western industrialized countries. Lifetime risk of colorectal cancer may reach 6% of the population living in developed countries. In the current era of personalized medicine, CRC is no longer considered as a single entity. In more recent years many studies have described the distinct differences in epidemiology, pathogenesis, genetic and epigenetic alterations, molecular pathways and outcome depending on the anatomical site. The aim of our study is to assess in a multidimensional model the association between metabolic status and inflammatory and autophagic changes in the normal colorectal mucosa classified as right-sided, left-sided and rectum, and the presence of adenomas. One hundred and sixteen patients undergoing colonoscopy were recruited and underwent a complete serum lipid profile, immunofluorescence analysis of colonic biopsies for MAPLC3 and myeloperoxidase expression, matched with clinical and anthropometric characteristics. Presence of adenomas correlated with cholesterol (total and LDL) levels, IL-6 levels, and MAPLC3 tissue expression, especially in the right colon. In conclusion, serum IL-6 amount and autophagic markers could be good predictors of the presence of colorectal adenomas.
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Affiliation(s)
- Paola Sena
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy;
| | - Stefano Mancini
- Department of Internal Medicine and Rehabilitation, Santa Maria Bianca Hospital, Mirandola 6, 41037 Modena, Italy;
| | - Monica Pedroni
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy; (M.P.); (L.R.B.); (L.R.)
| | - Luca Reggiani Bonetti
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy; (M.P.); (L.R.B.); (L.R.)
| | - Gianluca Carnevale
- Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy;
| | - Luca Roncucci
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy; (M.P.); (L.R.B.); (L.R.)
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Li H, Wang X, Huang X, He Y, Zhang Y, Hao C, Zeng P, Zhang M, Gao Y, Yang D, Shan M, Dou H, Li X, Chang X, Tian Z, Zhang L. Circulating Glycan Monosaccharide Composite-Based Biomarker Diagnoses Colorectal Cancer at Early Stages and Predicts Prognosis. Front Oncol 2022; 12:852044. [PMID: 35574422 PMCID: PMC9099097 DOI: 10.3389/fonc.2022.852044] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 04/06/2022] [Indexed: 12/29/2022] Open
Abstract
Introduction Early diagnosis could lead to a cure of colorectal cancer (CRC). Since CRC is related to aging and lifestyles, we tested if the environmental information-enriched monosaccharide composite (MC) of circulating glycans could serve as an early diagnostic biomarker for CRC. Meanwhile, we evaluated its role in predicting prognosis. Methods HPAEC-PAD was used to quantify glycan monosaccharide compositions from a total of 467 serum samples including CRC patients, colorectal adenoma (CRA) patients and healthy individuals. Two diagnostic model was constructed by logistic regression analysis. The diagnostic performance of the two models was verified in the retrospective validation group and the prospective validation group. The prognostic performance of the model was assessed by survival analysis. Results The concentrations of monosaccharides in serum were significantly higher in CRA and CRC patients than in healthy individuals. Two diagnostic models were constructed: MC1 was used to distinguish between healthy individuals and CRC; MC2 was used to distinguish between healthy individuals and CRA. Area under receptor operating characteristic curve (AUC) of MC2 and MC1 was 0.8025 and 0.9403 respectively. However, the AUC of CEA between healthy individuals and CRC was 0.7384. Moreover, in early stage of CRC (without lymph node metastasis), the positive rates of CEA and MC1 were 28% and 80%, respectively. The follow-up data showed that the increased MC1 value was associated with poor survival in patients with CRC (p=0.0010, HR=5.30). Discussion The MC1 model is superior to CEA in the diagnosis of CRC, especially in the early diagnosis. MC1 can be used for predicting prognosis of CRC patients, and elevated MC1 values indicate poor survival.
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Affiliation(s)
- Haoran Li
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xueling Wang
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
- Center for Clinical Research, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaodan Huang
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yanli He
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yiran Zhang
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
- Shandong Institute of Orthopedics and Traumatology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Cui Hao
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Pengjiao Zeng
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Meng Zhang
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yanyun Gao
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Dandan Yang
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Ming Shan
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Huaiqian Dou
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaoyu Li
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiaotian Chang
- Center for Clinical Research, The Affiliated Hospital of Qingdao University, Qingdao, China
- *Correspondence: Lijuan Zhang, ; Xiaotian Chang, ; Zibin Tian,
| | - Zibin Tian
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China
- *Correspondence: Lijuan Zhang, ; Xiaotian Chang, ; Zibin Tian,
| | - Lijuan Zhang
- Systems Biology & Medicine Center for Complex Diseases, The Affiliated Hospital of Qingdao University, Qingdao, China
- *Correspondence: Lijuan Zhang, ; Xiaotian Chang, ; Zibin Tian,
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Bonde A, Smith DA, Kikano E, Yoest JM, Tirumani SH, Ramaiya NH. Overview of serum and tissue markers in colorectal cancer: a primer for radiologists. Abdom Radiol (NY) 2021; 46:5521-5535. [PMID: 34415413 DOI: 10.1007/s00261-021-03243-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2021] [Revised: 08/05/2021] [Accepted: 08/07/2021] [Indexed: 12/17/2022]
Abstract
Serum and tissue tumor markers provide crucial information in the diagnosis, treatment, and follow-up of colorectal cancers. Tissue tumor markers are increasingly used for determination of targeted chemotherapy planning based on genotyping of tumor cells. Recently, plasma-based technique of liquid biopsy is being evaluated for providing tumor biomarkers in the management of colorectal cancer. Tumor markers are commonly used in conjunction with imaging during initial staging, treatment determination, response assessment, and determination of recurrence or metastatic disease. Knowledge of tumor markers and their association with radiological findings is thus crucial for radiologists. Additionally, various novel imaging techniques are being evaluated as potential noninvasive imaging biomarkers to predict tumor genotypes, features, and tumor response. We review and discuss the potential role of these newer imaging techniques.
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Affiliation(s)
- Apurva Bonde
- Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.
| | - Daniel A Smith
- Department of Radiology, University Hospitals Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA
| | - Elias Kikano
- Department of Radiology, University Hospitals Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA
| | - Jennifer M Yoest
- Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA
| | - Sree H Tirumani
- Department of Radiology, University Hospitals Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA
| | - Nikhil H Ramaiya
- Department of Radiology, University Hospitals Cleveland Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA
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Bialkowski K, Szpila A. Specific 8-oxo-dGTPase activity of MTH1 (NUDT1) protein as a quantitative marker and prognostic factor in human colorectal cancer. Free Radic Biol Med 2021; 176:257-264. [PMID: 34624481 DOI: 10.1016/j.freeradbiomed.2021.10.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 09/23/2021] [Accepted: 10/03/2021] [Indexed: 11/27/2022]
Abstract
The MTH1 (NUDT1) gene, because it is frequently upregulated in many types of human cancers, has been considered a general marker of carcinogenesis for over two decades. The MTH1 protein hydrolyzes the oxidized mutagenic DNA precursor, 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP), to the corresponding 5'-monophosphate and inorganic pyrophosphate. This prevents its incorporation into DNA by DNA polymerases and protects cells from the accumulation of 8-oxo-dGTP-induced point mutations. Elevated MTH1 mRNA and protein in many types of human cancer indicate a worse prognosis. However, the enzymatic activity of MTH1 has remained largely uninvestigated in this context. Therefore, we have set out to determine the specific 8-oxo-dGTPase activity of MTH1 in 57 pairs of human colorectal cancers (CRC) and adjacent cancer-free tissues (CFCF). The goal was to ascertain the potential for measuring this enzymatic activity as a way to differentiate cancerous from non-cancerous specimens of the intestine, as well as defining its capabilities as a prognostic value for disease-free survival. We found that 79% of CRC tumors exhibited a higher MTH1 activity than did CFCF, with a significant 1.6-fold increase in overall median value (p < 1E-6). The 8-oxo-dGTPase in both tissues was proportional to the corresponding levels of MTH1 protein, as assayed by Western blotting. Activity higher than the ROC-optimized threshold (AUC = 0.71) indicated cancerous tissue, with a 54% sensitivity and an 83% specificity. Postoperative fate followed for up to 100 months showed that higher 8-oxo-dGTPase, in either the CFCF or the CRC tumor, clearly lowered the probability of a relapse-free survival, although borderline statistical significance (p < 0.05) was crossed only for the CFCF.
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Affiliation(s)
- Karol Bialkowski
- Department of Clinical Biochemistry, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
| | - Anna Szpila
- Department of Clinical Biochemistry, L. Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz, Poland
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Tieng FYF, Abu N, Nasir SN, Lee LH, Ab Mutalib NS. Liquid Biopsy-Based Colorectal Cancer Screening via Surface Markers of Circulating Tumor Cells. Diagnostics (Basel) 2021; 11:2136. [PMID: 34829483 PMCID: PMC8618170 DOI: 10.3390/diagnostics11112136] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 11/15/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is ranked second for cancer-related deaths worldwide with approximately half of the patients being diagnosed at the late stages. The untimely detection of CRC results in advancement to the metastatic stage and nearly 90% of cancer-related deaths. The early detection of CRC is crucial to decrease its overall incidence and mortality rates. The recent introduction of circulating tumor cells (CTCs) has enabled a less invasive sampling method from liquid biopsies, besides revealing key information toward CRC metastasis. The current gold standard for CTC identification is the CellSearch® system (Veridex). This first-generation instrumentation relies on a single cell surface marker (CSM) to capture and count CTCs. Detection of CTCs allows the identification of patients at risk for metastasis, whereas CTC enumeration could improve risk assessment, monitoring of systemic therapy, and detection of therapy resistance in advanced metastatic CRC. In this review, we compared the pros and cons between single CSM-based CTC enrichment techniques and multi-marker-based systems. We also highlighted the challenges faced in the routine implementation of CSM-dependent CTC detection methods in CRC screening, prediction, prognosis, disease monitoring, and therapy selection toward precision medicine, as well as the dwelling on post-CTC analysis and characterization methods.
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Affiliation(s)
- Francis Yew Fu Tieng
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Nadiah Abu
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Siti Nurmi Nasir
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Learn-Han Lee
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University of Malaysia, Subang Jaya 47500, Selangor, Malaysia
| | - Nurul-Syakima Ab Mutalib
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University of Malaysia, Subang Jaya 47500, Selangor, Malaysia
- Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
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Aparicio C, Belver M, Enríquez L, Espeso F, Núñez L, Sánchez A, de la Fuente MÁ, González-Vallinas M. Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells. Int J Mol Sci 2021; 22:11781. [PMID: 34769211 PMCID: PMC8583883 DOI: 10.3390/ijms222111781] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/23/2021] [Accepted: 10/26/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is a global public health problem as it is the third most prevalent and the second most lethal cancer worldwide. Major efforts are underway to understand its molecular pathways as well as to define the tumour-associated antigens (TAAs) and tumour-specific antigens (TSAs) or neoantigens, in order to develop an effective treatment. Cell therapies are currently gaining importance, and more specifically chimeric antigen receptor (CAR)-T cell therapy, in which genetically modified T cells are redirected against the tumour antigen of interest. This immunotherapy has emerged as one of the most promising advances in cancer treatment, having successfully demonstrated its efficacy in haematological malignancies. However, in solid tumours, such as colon cancer, it is proving difficult to achieve the same results due to the shortage of TSAs, on-target off-tumour effects, low CAR-T cell infiltration and the immunosuppressive microenvironment. To address these challenges in CRC, new approaches are proposed, including combined therapies, the regional administration of CAR-T cells and more complex CAR structures, among others. This review comprehensively summarises the current landscape of CAR-T cell therapy in CRC from the potential tumour targets to the preclinical studies and clinical trials, as well as the limitations and future perspectives of this novel antitumour strategy.
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Affiliation(s)
| | | | | | | | | | | | | | - Margarita González-Vallinas
- Unidad de Excelencia Instituto de Biología y Genética Molecular (IBGM), University of Valladolid (UVa)-CSIC, 47003 Valladolid, Spain; (C.A.); (M.B.); (L.E.); (F.E.); (L.N.); (A.S.); (M.Á.d.l.F.)
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