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Yang J, Li ZX, Song MJ, Han SJ, Yang AJ, Zhang ZP, Sui CS, Qiao JL, Huang WH, He JQ. Prognostic value and therapeutic efficacy of interstitial circulating tumor cells in patients with advanced gastric cancer. World J Clin Oncol 2025; 16:101762. [DOI: 10.5306/wjco.v16.i5.101762] [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: 09/25/2024] [Revised: 03/08/2025] [Accepted: 04/08/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND The high mortality rate and recurrence/metastasis remain major challenges in the clinical management of gastric cancer (GC) patients. To optimize treatment stratification and management, there is an urgent need for efficient and non-invasive biomarkers. A meta-analysis on the prognostic role of circulating tumor cells (CTCs) in GC revealed a strong association between CTCs and patient prognosis. Among CTC subtypes, Interstitial CTCs (I-CTCs) exhibited the strongest invasiveness. This study innovatively investigated the expression profile of I-CTCs in advanced GC patients to evaluate their clinical utility.
AIM To evaluate the clinical utility of I-CTCs as a non-invasive prognostic biomarker in advanced GC. To investigate the correlation between I-CTC count thresholds and chemotherapy efficacy in advanced GC patients. To establish the potential of preoperative I-CTC profiling for optimizing treatment stratification and postoperative surveillance.
METHODS This study retrospectively analyzed 59 patients with advanced GC treated at the General Surgery Clinical Medical Center of Gansu Provincial Hospital between October 2019 and October 2020. The expression levels of I-CTCs were measured, and patient survival was monitored. The receiver operating characteristic curve was plotted to determine the optimal cut-off value for I-CTCs expression levels. Based on this cut-off value, 59 GC patients were grouped into positive and negative groups. The differences in clinicopathological characteristics between the two groups were analyzed. Patient survival was follow-up and recorded until October 2022. Plotting survival curves and performing univariate and multifactorial analyses of patient prognostic factors. The Kaplan-Meier method and Cox regression model were used, respectively.
RESULTS A total of 59 patients were included in this study, and receiver operating characteristic curve analysis showed that the best cut-off value for I-CTCs was 5, with an area under the curve of 0.8356 (95% confidence interval: 0.7122-0.9590). The I-CTC count of ≥ 5 defines the positive group, while counts < 5 are classified as the negative group. Positive I-CTCs correlated with the degree of tumor differentiation and disease progression (P < 0.05). 16 of 59 patients received neoadjuvant chemotherapy. There were divided into progressive disease and disease control groups based on response to neoadjuvant chemotherapy. Patients in the I-CTCs-negative group had longer overall survival and disease-free survival than those in the positive group (P < 0.05). Multifactorial analysis revealed that I-CTCs positivity (HR = 13.323, 95% confidence interval: 1.675-105.962, P = 0.014) was an independent risk factor for survival in patients with advanced GC.
CONCLUSION In patients with advanced GC, an I-CTC count of ≥ 5 is associated with both poor prognosis and reduced chemotherapy efficacy. I-CTCs may serve as a valuable preoperative biomarker for predicting the prognosis of advanced GC.
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Affiliation(s)
- Jing Yang
- Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, Guangdong Province, China
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730030, Gansu Province, China
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730030, Gansu Province, China
| | - Zu-Xi Li
- Department of Peripheral Vascular Intervention, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730060, Gansu Province, China
| | - Mei-Juan Song
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Shang-Jun Han
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Ai-Jia Yang
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Ze-Ping Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Chang-Sheng Sui
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Ji-Lin Qiao
- The First Clinical Medical College of Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Wen-Hua Huang
- Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, Guangdong Province, China
| | - Jun-Qiang He
- Department of General Surgery, Xinhui People’s Hospital of Southern Medical University, Jiangmen 529000, Guangdong Province, China
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Mastronicola R, Kayser E, Le Roux P, Barrat A, Aubertin A, Casse A, Nominé L, Villard H, Cortese S, Beulque E, Merlin JL, Dolivet G. Study of the survival of patients with head and neck cancer in relation to Circulating Tumor Cells (CTCs). PLoS One 2025; 20:e0320485. [PMID: 40168331 PMCID: PMC11960953 DOI: 10.1371/journal.pone.0320485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 02/19/2025] [Indexed: 04/03/2025] Open
Abstract
Distant metastasis in head and neck cancer are one of the first factors contributing to death. Currently, it is difficult to detect them early with our conventional techniques such as Positron Emission Tomography scanner (PET-scanner) and Magnetic Resonance Imaging (MRI). Therefore, it is important to find new markers that can help us in the care of the patient. This study aimed at comparing two methods (Reverse Transcription-Polymerase Chain Reaction and CellSearch) to detect circulating tumor cells (CTC) as a prognosticator. Results were statistically significant for markers EphB4 (p-value = 0.0003), CEA (p-value = 0.0006), CK 18 (p-value = 0.0011) and Ep-CAM (p-value = 0.0299) and demonstrate that our detection techniques could be used by optimizing our protocol. In addition, results of the rate of CTCs helped identify this as an indicator of a prognosis for the patient. Indeed, the study revealed that most patients in remission exhibited a decrease in post-operative CTCs, whereas patients experiencing relapses demonstrated an increase in CTCs, which was correlated with a poor prognosis.
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Affiliation(s)
- Romina Mastronicola
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
- CRAN, CNRS, UMR, Université de Lorraine, Vandœuvre-lès-Nancy, France
| | - Elise Kayser
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
| | - Pauline Le Roux
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
| | - Agathe Barrat
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
| | | | - Aurore Casse
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
| | - Léa Nominé
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
| | - Hélèna Villard
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
| | - Sophie Cortese
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
| | - Emilie Beulque
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
| | - Jean-Louis Merlin
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
- CRAN, CNRS, UMR, Université de Lorraine, Vandœuvre-lès-Nancy, France
| | - Gilles Dolivet
- Institut de Cancérologie de Lorraine ICL, Vandœuvre-lès-Nancy, France
- CRAN, CNRS, UMR, Université de Lorraine, Vandœuvre-lès-Nancy, France
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Zhang H, Jiao J, Long Y, Zhou L, Lv Y, Wei W, Sun Y, Han H, Chen C, Zhu Y, Zhang W. Targeting capture and eradicate circulating tumor cells by activated platelet derived vehicle for inhibiting triple-negative breast cancer metastasis. Mater Today Bio 2025; 31:101597. [PMID: 40092226 PMCID: PMC11910114 DOI: 10.1016/j.mtbio.2025.101597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 02/05/2025] [Accepted: 02/18/2025] [Indexed: 03/19/2025] Open
Abstract
Circulating tumor cells (CTCs) are cardinal intermediaries in the metastatic cascade, particularly in triple-negative breast cancer (TNBC), owing to their high-affinity interactions that bolster survival and dissemination. Addressing this pivotal mechanism, we have developed APEVs@DOX, a pioneering biomimetic delivery system. Utilizing activated platelet membranes as a scaffold, APEVs@DOX recapitulates the natural affinity between platelets and CTCs, enabling targeted delivery of doxorubicin. Our results, substantiated by meticulous in vitro and in vivo experimentation, revealed 78 % reduction in lung metastasis nodules in murine models relative to controls, affirming APEVs@DOX's proficiency in CTCs capture and eradication. This study not only illuminates the potential of CTCs-targeted therapies in the precision medicine armamentarium for TNBC but also contributes empirical data to guide the strategic design of anti-metastatic interventions. The therapeutic impact of APEVs@DOX in curtailing metastatic spread offers a beacon of hope for advancing TNBC treatment paradigms.
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Affiliation(s)
- Hongmei Zhang
- Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, 210000, China
- Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210000, China
- Gansu Wuwei Institute of Medical Sciences, Gansu, 733000, China
| | - Jinlan Jiao
- Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, 210000, China
| | - Yongxuan Long
- Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, 210000, China
| | - Lina Zhou
- Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210000, China
| | - Yinhua Lv
- Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210000, China
| | - Wenqian Wei
- Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210000, China
| | - Yuxiang Sun
- Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, China
| | - Hao Han
- Department of Ultrasound, Nanjing Drum Tower Hospital, The Affiliated Hospital of NanJing University Medical School, Nanjing, 210000, China
| | - Changrong Chen
- Department of Emergency Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210000, China
| | - Yun Zhu
- Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, 210000, China
- Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210000, China
- Nanjing Medical Center for Clinical Pharmacy, Nanjing, Jiangsu, 210000, China
| | - Weijie Zhang
- Division of Breast Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, 210000, China
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Aigner K, Selak E, Pizon M, Aigner KR. Arterial Infusion and Isolated Perfusion in Combination with Reversible Electroporation for Locally Relapsed Unresectable Breast Cancer. Cancers (Basel) 2024; 16:3991. [PMID: 39682178 DOI: 10.3390/cancers16233991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 11/21/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Relapsed unresectable triple-negative breast cancer is a demanding disease with only a few treatment options. Especially for patients with unresectable tumor masses, a treatment that offers rapid tumor shrinkage is needed. If patients are exhausted from several treatment lines, systemic side effects have to be avoided. Reversible electroporation has shown to be effective for breast cancer if combined with systemic bleomycin and/or cisplatin. To enhance the local effect and reduce the systemic side effects, we combined reversible electroporation with regional chemotherapy. MATERIALS AND METHODS Patients with advanced metastasized and relapsed breast cancer received regional chemotherapy via intra-arterial infusion and isolated thoracic perfusion combined with percutanous reversible electroporation. Circulating tumor cells (CETCs/CTCs) were counted before and 24 h after the treatment. Tumor response was evaluated by CT (computer tomography) control. RESULTS A total of 21 treatments were conducted for 14 patients who had a mean tumor size of 7.6 cm (standard deviation 3.3 cm). Higher local drug levels are present with arterial infusion compared to venous infusion and result in enhanced response rates. Circulating tumor cells decreased or stayed stable for 24 h after the treatment for 11 and 8 cases, respectively. An increase was observed in two cases. A total of 13 patients showed a clinical response with tumor shrinkage that led to resectability. One patient did not respond to the treatment regimen. CONCLUSIONS The combination of reversible electroporation with intra-arterial chemotherapy is feasible and results in a good clinical response with neglectable side effects. The treatment is repeatable and can lead to resectability.
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Affiliation(s)
- Kornelia Aigner
- Department Tumor Biology, Medias Klinikum, 84489 Burghausen, Germany
| | - Emir Selak
- Department Surgical Oncology, Medias Klinikum, 84489 Burghausen, Germany
| | - Monika Pizon
- Transfusionsmedizinisches Zentrum, 95448 Bayreuth, Germany
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Jiang J, Mo W, Lian X, Cao D, Cheng H, Wang H. Detection of PD‑L1 expression and epithelial‑mesenchymal transition of circulating tumor cells in non‑small cell lung cancer. Exp Ther Med 2024; 28:294. [PMID: 38827467 PMCID: PMC11140314 DOI: 10.3892/etm.2024.12583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 04/18/2024] [Indexed: 06/04/2024] Open
Abstract
The present study aimed to assess the roles of peripheral circulating tumor cell (CTC) count, CTC subtypes and programmed death ligand 1 (PD-L1) expression in the clinical staging and prognosis of patients with non-small cell lung cancer (NSCLC). A total of 100 patients with NSCLC with available tumor tissues were enrolled in the present study, and 7.5 ml peripheral blood was collected. Patients were divided into PD-L1-positive and PD-L1-negative groups according to PD-L1 immunohistochemical staining. Peripheral blood samples from both groups were analyzed to determine the CTC count, epithelial-type CTCs (E-CTCs), mesenchymal-type CTCs (M-CTCs) and PD-L1 expression. Clinical data were collected, and patients were followed up for a maximum of 36 months, with patient death as the endpoint event. Patients with PD-L1-positive tumors had a worse prognosis compared with those with PD-L1-negative tumors (P=0.045). The PD-L1-positive group exhibited significantly higher numbers of CTCs and M-CTCs compared with the PD-L1-negative group (P≤0.05). However, the number of E-CTCs did not differ significantly between the two groups (P>0.05). PD-L1-positive patients with higher CTC and M-CTC counts had relatively poorer prognoses (P≤0.05), while the number of E-CTCs had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the CTC count (P≤0.05), while E-CTC and M-CTC counts did not significantly differ between the two groups (P>0.05). The PD-L1-positive group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs compared with the PD-L1-negative group (P≤0.05), while PD-L1+ E-CTC counts did not differ significantly between the two groups (P>0.05). The PD-L1-positive patients with a higher number of PD-L1+ CTCs and PD-L1+ M-CTCs had relatively poorer prognoses (P≤0.05), while the PD-L1+ E-CTC count had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs (P≤0.05), while PD-L1+ E-CTC counts did not significantly differ between the two groups (P>0.05). Based on univariate and multivariate analyses, the number of PD-L1+ M-CTCs was identified as an independent prognostic factor for NSCLC. In conclusion, the presence of CTCs in peripheral blood, particularly PD-L1+ M-CTC subtype, indicated poorer clinical staging and prognosis in patients with NSCLC. These findings suggested that CTCs, specifically the PD-L1+ M-CTC subtype, could serve as a monitoring indicator for the clinical staging and prognosis of patients with NSCLC.
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Affiliation(s)
- Jianping Jiang
- Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Weiqiang Mo
- Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Xue Lian
- Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Dakui Cao
- Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Haiying Cheng
- Department of Nursing Administration, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
| | - Haiqin Wang
- Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang 314000, P.R. China
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Sayed ZS, Khattap MG, Madkour MA, Yasen NS, Elbary HA, Elsayed RA, Abdelkawy DA, Wadan AHS, Omar I, Nafady MH. Circulating tumor cells clusters and their role in Breast cancer metastasis; a review of literature. Discov Oncol 2024; 15:94. [PMID: 38557916 PMCID: PMC10984915 DOI: 10.1007/s12672-024-00949-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 03/21/2024] [Indexed: 04/04/2024] Open
Abstract
Breast cancer is a significant and deadly threat to women globally. Moreover, Breast cancer metastasis is a complicated process involving multiple biological stages, which is considered a substantial cause of death, where cancer cells spread from the original tumor to other organs in the body-representing the primary mortality factor. Circulating tumor cells (CTCs) are cancer cells detached from the primary or metastatic tumor and enter the bloodstream, allowing them to establish new metastatic sites. CTCs can travel alone or in groups called CTC clusters. Studies have shown that CTC clusters have more potential for metastasis and a poorer prognosis than individual CTCs in breast cancer patients. However, our understanding of CTC clusters' formation, structure, function, and detection is still limited. This review summarizes the current knowledge of CTC clusters' biological properties, isolation, and prognostic significance in breast cancer. It also highlights the challenges and future directions for research and clinical application of CTC clusters.
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Affiliation(s)
- Zeinab S Sayed
- Faculty of Applied Medical Science, Misr University for Science and Technology, 26Th of July Corridor, 6Th of October, Giza Governorate, Postal Code: 77, Egypt
| | - Mohamed G Khattap
- Technology of Radiology and Medical Imaging Program, Faculty of Applied Health Sciences Technology, Galala University, Suez, 435611, Egypt
| | | | - Noha S Yasen
- Radiology and Imaging Technology Department, Faculty of Applied Health Science Technology, Delta University for Science and Technology, Gamasa, Al Mansurah, Egypt
| | - Hanan A Elbary
- Faculty of Applied Medical Science, Misr University for Science and Technology, 26Th of July Corridor, 6Th of October, Giza Governorate, Postal Code: 77, Egypt
| | - Reem A Elsayed
- Faculty of Applied Medical Science, Misr University for Science and Technology, 26Th of July Corridor, 6Th of October, Giza Governorate, Postal Code: 77, Egypt
| | - Dalia A Abdelkawy
- Faculty of Applied Medical Science, Misr University for Science and Technology, 26Th of July Corridor, 6Th of October, Giza Governorate, Postal Code: 77, Egypt
| | | | - Islam Omar
- Faculty of Pharmacy, South Valley University, Qena, Egypt
| | - Mohamed H Nafady
- Radiation Sciences Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
- Faculty of Applied Health Science Technology, Misr University for Science and Technology, 6th of october, Egypt.
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Pu X, Zhang C, Ding G, Gu H, Lv Y, Shen T, Pang T, Cao L, Jia S. Diagnostic plasma small extracellular vesicles miRNA signatures for pancreatic cancer using machine learning methods. Transl Oncol 2024; 40:101847. [PMID: 38035445 PMCID: PMC10730862 DOI: 10.1016/j.tranon.2023.101847] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 11/14/2023] [Accepted: 11/20/2023] [Indexed: 12/02/2023] Open
Abstract
BACKGROUND Identifying biomarkers may lead to easier detection and a better understanding of pathogenesis of pancreatic ductal adenocarcinoma (PDAC). METHODS Plasma small extracellular vesicles (sEV) from 106 participants, including 20 healthy controls (HC), 12 chronic pancreatitis (CP) patients, 12 benign pancreatic tumour (BPT) patients, and 58 PDAC patients, were profiled for microRNA (miRNA) sequencing. Three machine learning methods were applied to establish and evaluate the diagnostic model. RESULTS The plasma sEV miRNA diagnostic signature (d-signature) selected using the three machine learning methods could distinguish PDAC patients from non-PDAC individuals, HC, and benign pancreatic disease (BPD, CP plus BPT) both in training and validation cohort. Combining the d-signature with carbohydrate antigen 19-9 (CA19-9) performed better than with each model alone. Plasma sEV miR-664a-3p was selected by all methods and used to predict PDAC diagnosis with high accuracy combined with CA19-9. Plasma sEV miR-664a-3p was significantly positively associated with the presence of vascular invasion, lower surgery ratio, and poor differentiation. MiR-664a-3p was mainly distributed in the PDAC cancer stroma, including fibers and vessels, and was accompanied by VEGFA expression. Overexpression of miR-664a-3p could promote the epithelial-mesenchymal transition (EMT) and angiogenesis. CONCLUSION In conclusion, our study demonstrated the potential utility of the sEV-miRNA d-signature in the diagnosis of PDAC via machine learning methods. A novel sEV biomarker, miR-664a-3p, was identified for the diagnosis of PDAC. It can also potentially promote angiogenesis and metastasis, provide insight into PDAC pathogenesis, and reveal novel regulators of this disease.
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Affiliation(s)
- Xiaofan Pu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Chaolei Zhang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Guoping Ding
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Hongpeng Gu
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Yang Lv
- Department of Emergency Medicine, Sir Run Run Shaw Hospital Xiasha Campus, School of Medicine, Zhejiang University, Hangzhou, China
| | - Tao Shen
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Tianshu Pang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Liping Cao
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Engineering Research Center of Cognitive Healthcare, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China.
| | - Shengnan Jia
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
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Wang X, Wang L, Lin H, Zhu Y, Huang D, Lai M, Xi X, Huang J, Zhang W, Zhong T. Research progress of CTC, ctDNA, and EVs in cancer liquid biopsy. Front Oncol 2024; 14:1303335. [PMID: 38333685 PMCID: PMC10850354 DOI: 10.3389/fonc.2024.1303335] [Citation(s) in RCA: 25] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 01/04/2024] [Indexed: 02/10/2024] Open
Abstract
Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vehicles (EVs) have received significant attention in recent times as emerging biomarkers and subjects of transformational studies. The three main branches of liquid biopsy have evolved from the three primary tumor liquid biopsy detection targets-CTC, ctDNA, and EVs-each with distinct benefits. CTCs are derived from circulating cancer cells from the original tumor or metastases and may display global features of the tumor. ctDNA has been extensively analyzed and has been used to aid in the diagnosis, treatment, and prognosis of neoplastic diseases. EVs contain tumor-derived material such as DNA, RNA, proteins, lipids, sugar structures, and metabolites. The three provide different detection contents but have strong complementarity to a certain extent. Even though they have already been employed in several clinical trials, the clinical utility of three biomarkers is still being studied, with promising initial findings. This review thoroughly overviews established and emerging technologies for the isolation, characterization, and content detection of CTC, ctDNA, and EVs. Also discussed were the most recent developments in the study of potential liquid biopsy biomarkers for cancer diagnosis, therapeutic monitoring, and prognosis prediction. These included CTC, ctDNA, and EVs. Finally, the potential and challenges of employing liquid biopsy based on CTC, ctDNA, and EVs for precision medicine were evaluated.
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Affiliation(s)
- Xiaoling Wang
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
| | - Lijuan Wang
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
| | - Haihong Lin
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
| | - Yifan Zhu
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
| | - Defa Huang
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Mi Lai
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Xuxiang Xi
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
| | - Junyun Huang
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
| | - Wenjuan Zhang
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
| | - Tianyu Zhong
- Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
- The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China
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Lopez-Gonzalez L, Sanchez Cendra A, Sanchez Cendra C, Roberts Cervantes ED, Espinosa JC, Pekarek T, Fraile-Martinez O, García-Montero C, Rodriguez-Slocker AM, Jiménez-Álvarez L, Guijarro LG, Aguado-Henche S, Monserrat J, Alvarez-Mon M, Pekarek L, Ortega MA, Diaz-Pedrero R. Exploring Biomarkers in Breast Cancer: Hallmarks of Diagnosis, Treatment, and Follow-Up in Clinical Practice. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:168. [PMID: 38256428 PMCID: PMC10819101 DOI: 10.3390/medicina60010168] [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: 12/12/2023] [Revised: 01/02/2024] [Accepted: 01/09/2024] [Indexed: 01/24/2024]
Abstract
Breast cancer is a prevalent malignancy in the present day, particularly affecting women as one of the most common forms of cancer. A significant portion of patients initially present with localized disease, for which curative treatments are pursued. Conversely, another substantial segment is diagnosed with metastatic disease, which has a worse prognosis. Recent years have witnessed a profound transformation in the prognosis for this latter group, primarily due to the discovery of various biomarkers and the emergence of targeted therapies. These biomarkers, encompassing serological, histological, and genetic indicators, have demonstrated their value across multiple aspects of breast cancer management. They play crucial roles in initial diagnosis, aiding in the detection of relapses during follow-up, guiding the application of targeted treatments, and offering valuable insights for prognostic stratification, especially for highly aggressive tumor types. Molecular markers have now become the keystone of metastatic breast cancer diagnosis, given the diverse array of chemotherapy options and treatment modalities available. These markers signify a transformative shift in the arsenal of therapeutic options against breast cancer. Their diagnostic precision enables the categorization of tumors with elevated risks of recurrence, increased aggressiveness, and heightened mortality. Furthermore, the existence of therapies tailored to target specific molecular anomalies triggers a cascade of changes in tumor behavior. Therefore, the primary objective of this article is to offer a comprehensive review of the clinical, diagnostic, prognostic, and therapeutic utility of the principal biomarkers currently in use, as well as of their clinical impact on metastatic breast cancer. In doing so, our goal is to contribute to a more profound comprehension of this complex disease and, ultimately, to enhance patient outcomes through more precise and effective treatment strategies.
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Affiliation(s)
- Laura Lopez-Gonzalez
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (L.L.-G.); (A.M.R.-S.); (S.A.-H.); (R.D.-P.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
| | - Alicia Sanchez Cendra
- Oncology Service, Guadalajara University Hospital, 19002 Guadalajara, Spain; (A.S.C.); (C.S.C.); (E.D.R.C.); (J.C.E.)
| | - Cristina Sanchez Cendra
- Oncology Service, Guadalajara University Hospital, 19002 Guadalajara, Spain; (A.S.C.); (C.S.C.); (E.D.R.C.); (J.C.E.)
| | | | - Javier Cassinello Espinosa
- Oncology Service, Guadalajara University Hospital, 19002 Guadalajara, Spain; (A.S.C.); (C.S.C.); (E.D.R.C.); (J.C.E.)
| | - Tatiana Pekarek
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (T.P.); (L.J.-Á.)
| | - Oscar Fraile-Martinez
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (T.P.); (L.J.-Á.)
| | - Cielo García-Montero
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (T.P.); (L.J.-Á.)
| | - Ana María Rodriguez-Slocker
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (L.L.-G.); (A.M.R.-S.); (S.A.-H.); (R.D.-P.)
| | - Laura Jiménez-Álvarez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (T.P.); (L.J.-Á.)
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Universitary Hospital, 28805 Alcala de Henares, Spain
| | - Luis G. Guijarro
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
- Unit of Biochemistry and Molecular Biology, Department of System Biology (CIBEREHD), University of Alcalá, 28801 Alcala de Henares, Spain
| | - Soledad Aguado-Henche
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (L.L.-G.); (A.M.R.-S.); (S.A.-H.); (R.D.-P.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
| | - Jorge Monserrat
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (T.P.); (L.J.-Á.)
| | - Melchor Alvarez-Mon
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (T.P.); (L.J.-Á.)
- Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine (CIBEREHD), University Hospital Príncipe de Asturias, 28806 Alcala de Henares, Spain
| | - Leonel Pekarek
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
- Oncology Service, Guadalajara University Hospital, 19002 Guadalajara, Spain; (A.S.C.); (C.S.C.); (E.D.R.C.); (J.C.E.)
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (T.P.); (L.J.-Á.)
| | - Miguel A. Ortega
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (T.P.); (L.J.-Á.)
- Cancer Registry and Pathology Department, Principe de Asturias University Hospital, 28806 Alcala de Henares, Spain
| | - Raul Diaz-Pedrero
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain; (L.L.-G.); (A.M.R.-S.); (S.A.-H.); (R.D.-P.)
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain; (O.F.-M.); (C.G.-M.); (L.G.G.); (M.A.-M.); (L.P.); (M.A.O.)
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Universitary Hospital, 28805 Alcala de Henares, Spain
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Pekarek L, Sánchez Cendra A, Roberts Cervantes ED, Sánchez Cendra C, Fraile-Martinez O, García-Montero C, Diaz-Pedrero R, Torres-Carranza D, Lopez-Gonzalez L, Aguado-Henche S, Rios-Parra A, García-Puente LM, García-Honduvilla N, Bujan J, Alvarez-Mon M, Saez MA, Ortega MA. Clinical and Translational Applications of Serological and Histopathological Biomarkers in Metastatic Breast Cancer: A Comprehensive Review. Int J Mol Sci 2023; 24:ijms24098396. [PMID: 37176102 PMCID: PMC10178988 DOI: 10.3390/ijms24098396] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 04/27/2023] [Accepted: 05/05/2023] [Indexed: 05/15/2023] Open
Abstract
Breast cancer is one of the most common malignancies worldwide and the most common form of cancer in women. A large proportion of patients begin with localized disease and undergo treatment with curative intent, while another large proportion of patients debuts with disseminated metastatic disease. In the last subgroup of patients, the prognosis in recent years has changed radically, given the existence of different targeted therapies thanks to the discovery of different biomarkers. Serological, histological, and genetic biomarkers have demonstrated their usefulness in the initial diagnosis, in the follow-up to detect relapses, to guide targeted treatment, and to stratify the prognosis of the most aggressive tumors in those with breast cancer. Molecular markers are currently the basis for the diagnosis of metastatic disease, given the wide variety of chemotherapy regions and existing therapies. These markers have been a real revolution in the therapeutic arsenal for breast cancer, and their diagnostic validity allows the classification of tumors with higher rates of relapse, aggressiveness, and mortality. In this sense, the existence of therapies targeting different molecular alterations causes a series of changes in tumor biology that can be assessed throughout the course of the disease to provide information on the underlying pathophysiology of metastatic disease, which allows us to broaden our knowledge of the different mechanisms of tissue invasion. Therefore, the aim of the present article is to review the clinical, diagnostic, predictive, prognostic utility and limitations of the main biomarkers available and under development in metastatic breast cancer.
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Affiliation(s)
- Leonel Pekarek
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Oncology Service, Guadalajara University Hospital, 19002 Guadalajara, Spain
| | | | | | | | - Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Cielo García-Montero
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Raul Diaz-Pedrero
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Department of General and Digestive Surgery, General and Digestive Surgery, Príncipe de Asturias Universitary Hospital, 28805 Alcala de Henares, Spain
| | - Diego Torres-Carranza
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
| | - Laura Lopez-Gonzalez
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
| | - Soledad Aguado-Henche
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
| | - Antonio Rios-Parra
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Pathological Anatomy Service, University Hospital Príncipe de Asturias, 28806 Alcala de Henares, Spain
| | - Luis M García-Puente
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Natalio García-Honduvilla
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Julia Bujan
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
| | - Melchor Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Immune System Diseases-Rheumatology, Oncology Service an Internal Medicine (CIBEREHD), University Hospital Príncipe de Asturias, 28806 Alcala de Henares, Spain
| | - Miguel A Saez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Pathological Anatomy Service, Central University Hospital of Defence-UAH Madrid, 28801 Alcala de Henares, Spain
| | - Miguel A Ortega
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcala de Henares, Spain
- Ramón y Cajal Institute of Sanitary Research (IRYCIS), 28034 Madrid, Spain
- Cancer Registry and Pathology Department, Principe de Asturias University Hospital, 28806 Alcala de Henares, Spain
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Liang L, Kaufmann AM. The Significance of Cancer Stem Cells and Epithelial-Mesenchymal Transition in Metastasis and Anti-Cancer Therapy. Int J Mol Sci 2023; 24:ijms24032555. [PMID: 36768876 PMCID: PMC9917228 DOI: 10.3390/ijms24032555] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
Cancer stem cells (CSCs) have been identified and characterized in both hematopoietic and solid tumors. Their existence was first predicted by Virchow and Cohnheim in the 1870s. Later, many studies showed that CSCs can be identified and isolated by their expression of specific cell markers. The significance of CSCs with respect to tumor biology and anti-cancer treatment lies in their ability to maintain quiescence with very slow proliferation, indefinite self-renewal, differentiation, and trans-differentiation such as epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET). The ability for detachment, migration, extra- and intravasation, invasion and thereby of completing all necessary steps of the metastatic cascade highlights their significance for metastasis. CSCs comprise the cancer cell populations responsible for tumor growth, resistance to therapies and cancer metastasis. In this review, the history of the CSC theory, their identification and characterization and their biology are described. The contribution of the CSC ability to undergo EMT for cancer metastasis is discussed. Recently, novel strategies for drug development have focused on the elimination of the CSCs specifically. The unique functional and molecular properties of CSCs are discussed as possible therapeutic vulnerabilities for the development of novel anti-metastasis treatments. Prospectively, this may provide precise personalized anti-cancer treatments with improved therapeutic efficiency with fewer side effects and leading to better prognosis.
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Fuloria S, Subramaniyan V, Gupta G, Sekar M, Meenakshi DU, Sathasivam K, Sudhakar K, Alharbi KS, Almutairi SS, Almalki WH, Fuloria NK. Detection of Circulating Tumor Cells and Epithelial Progenitor Cells: A Comprehensive Study. J Environ Pathol Toxicol Oncol 2023; 42:1-29. [PMID: 37017676 DOI: 10.1615/jenvironpatholtoxicoloncol.2022044456] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Technological advancement to enhance tumor cells (TC) has allowed discovery of various cellular bio-markers: cancer stem cells (CSC), circulating tumor cells (CTC), and endothelial progenitor cells (EPC). These are responsible for resistance, metastasis, and premetastatic conditions of cancer. Detection of CSC, CTC, and EPC assists in early diagnosis, recurrence prediction, and treatment efficacy. This review describes various methods to detect TC subpopulations such as in vivo assays (sphere-forming, serial dilution, and serial transplantation), in vitro assays (colony-forming cells, microsphere, side-population, surface antigen staining, aldehyde dehydrogenase activity, and Paul Karl Horan label-retaining cells, surface markers, nonenriched and enriched detection), reporter systems, and other analytical methods (flow cytometry, fluorescence microscopy/spectroscopy, etc.). The detailed information on methods to detect CSC, CTC, and EPC in this review will assist investigators in successful prognosis, diagnosis, and cancer treatment with greater ease.
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Affiliation(s)
- Shivkanya Fuloria
- Faculty of Pharmacy /Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah 08100, Malaysia
| | - Vetriselvan Subramaniyan
- Faculty of Medicine, Bioscience and Nursing, MAHSA University, Bandar Saujana Putra, 42610 Jenjarom Selangor, Malaysia
| | - Gaurav Gupta
- Department of Pharmacology, Suresh GyanVihar University, Jagatpura, Jaipur, India; Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical Sciences, Saveetha University, Chennai, India; Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Mahendran Sekar
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh 30450, Perak, Malaysia
| | | | | | - Kalvatala Sudhakar
- School of Pharmaceutical Sciences (LIT-Pharmacy), Lovely Professional University, Jalandhar 144411, India
| | - Khalid Saad Alharbi
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Al-Jouf, Saudi Arabia
| | | | - Waleed Hassan Almalki
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Neeraj Kumar Fuloria
- Faculty of Pharmacy/Centre of Excellence for Biomaterials Engineering, AIMST University, Kedah 08100, Malaysia
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Mäurer M, Schott D, Pizon M, Drozdz S, Wendt T, Wittig A, Pachmann K. Increased Circulating Epithelial Tumor Cells (CETC/CTC) over the Course of Adjuvant Radiotherapy Is a Predictor of Less Favorable Outcome in Patients with Early-Stage Breast Cancer. Curr Oncol 2022; 30:261-273. [PMID: 36661670 PMCID: PMC9857667 DOI: 10.3390/curroncol30010021] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Adjuvant radiotherapy (RT) is an integral component of a multidisciplinary treatment strategy for early-stage breast cancer. It significantly reduces the incidence of loco-regional recurrence but also of distant events. Distant events are due to tumor cells disseminated from the primary tumor into lymphatic fluid or blood, circulating epithelial tumor cells (CETC/CTC), which can reach distant tissues and regrow into metastases. The purpose of this study is to determine changes in the number of CETC/CTC in the course of adjuvant RT, and to evaluate whether they are correlated to local recurrence and distant metastases in breast cancer patients. METHODS Blood from 165 patients irradiated between 2002 and 2012 was analyzed 0-6 weeks prior to and 0-6 weeks after RT using the maintrac® method, and patients were followed over a median period of 8.97 (1.16-19.09) years. RESULTS Patients with an increase in CETC/CTC numbers over the course of adjuvant RT had a significantly worse disease-free survival (p = 0.004) than patients with stable or decreasing CETC/CTC numbers. CETC/CTC behavior was the most important factor in predicting subsequent relapse-free survival. In particular, patients who had received neoadjuvant chemotherapy were disproportionately more likely to develop metastases when cell counts increased over the course of RT (p = 0.003; hazard ratio 4.886). CONCLUSIONS Using the maintrac® method, CETC/CTC were detected in almost all breast cancer patients after surgery. The increase in CETC/CTC numbers over the course of RT represents a potential predictive biomarker to judge relative risk/benefit in patients with early breast cancer. The results of this study highlight the need for prospective clinical trials on CETC/CTC status as a predictive criterion and for individualization of treatment. CLINICAL TRIAL REGISTRATION The trial is registered (2 May 2019) at trials.gov under NCT03935802.
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Affiliation(s)
- Matthias Mäurer
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743 Jena, Germany
- Clinician Scientist Program OrganAge, Interdisciplinary Center for Clinical Research (IZKF), Jena University Hospital, 07747 Jena, Germany
| | - Dorothea Schott
- Transfusionsmedizinisches Zentrum Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany
| | - Monika Pizon
- Transfusionsmedizinisches Zentrum Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany
| | - Sonia Drozdz
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743 Jena, Germany
| | - Thomas Wendt
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743 Jena, Germany
| | - Andrea Wittig
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743 Jena, Germany
| | - Katharina Pachmann
- Transfusionsmedizinisches Zentrum Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany
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Gianni C, Palleschi M, Merloni F, Bleve S, Casadei C, Sirico M, Di Menna G, Sarti S, Cecconetto L, Mariotti M, De Giorgi U. Potential Impact of Preoperative Circulating Biomarkers on Individual Escalating/de-Escalating Strategies in Early Breast Cancer. Cancers (Basel) 2022; 15:96. [PMID: 36612091 PMCID: PMC9817806 DOI: 10.3390/cancers15010096] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 12/18/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
The research on non-invasive circulating biomarkers to guide clinical decision is in wide expansion, including the earliest disease settings. Several new intensification/de-intensification strategies are approaching clinical practice, personalizing the treatment for each patient. Moreover, liquid biopsy is revealing its potential with multiple techniques and studies available on circulating biomarkers in the preoperative phase. Inflammatory circulating cells, circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and other biological biomarkers are improving the armamentarium for treatment selection. Defining the escalation and de-escalation of treatments is a mainstay of personalized medicine in early breast cancer. In this review, we delineate the studies investigating the possible application of these non-invasive tools to give a more enlightened approach to escalating/de-escalating strategies in early breast cancer.
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Affiliation(s)
- Caterina Gianni
- Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy
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Li Z, Song M, Han S, Jin C, Yang J. The prognostic role of circulating tumor cells in gastric cancer: A meta-analysis. Front Oncol 2022; 12:963091. [PMID: 36313657 PMCID: PMC9610107 DOI: 10.3389/fonc.2022.963091] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE We conducted a meta-analysis to evaluate the relationship between circulating tumor cells (CTC) and the prognosis of patients with gastric cancer. MATERIALS AND METHODS The cohort studies reporting on the relationship between CTC and prognosis of gastric cancer were collected from Pubmed, Cochrane, Embase, CNKI, WanFang Data, and VIP databases. The two researchers independently screened the literature, extracted the data, and evaluated the bias risk of the included literature. The data were analyzed by Revman software (Review Manager version 5.4). RESULT A total of 14 retrospective cohort studies with 1053 patients were included. The results showed that the overall survival time (OS) and progression-free survival time (PFS) of CTC-positive patients were shorter compared to CTC-negative patients. Taking into consideration the critical value of CTC positive patients, country of origin, sample size, treatment mode, and study time, the subgroup analysis showed that CTC-positive was related to the shortening of OS in patients with gastric cancer. Based on the subgroup analysis of the factors such as CTC positive critical value < 2.8, sample size ≥ 75, mixed therapy, longer study duration, country, and immunofluorescence detection of CTC, it was found that OS in CTC positive group was shorter than that in CTC-negative group (all P<0.05), while the critical value of positive CTC ≥ 2.8, sample size ≥ 75, choice of treatment only for operation or non-operation, short study time and molecular detection of CTC were not associated with OS (all P>0.05). In addition, CTC-positive patients had a more advanced TNM staging, poorer tumor differentiation, and earlier distant metastasis. CONCLUSION CTC can be used as a prognostic indicator of gastric cancer. Gastric cancer patients with positive CTC may have a poorer prognosis compared to those with CTC-negative tumors. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022323155.
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Affiliation(s)
- Zuxi Li
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
| | - Meijuan Song
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
| | - Shangjun Han
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
| | - Chuanwei Jin
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
| | - Jing Yang
- The First Clinical School of Gansu University of Chinese Medicine, Lanzhou, China
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China
- Gansu Provincial Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumors, Gansu Provincial Hospital, Lanzhou, China
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Shao X, Jin X, Chen Z, Zhang Z, Chen W, Jiang J, Wang Z, Cui Y, Fan WH, Wang K, Yu X, Huang J. A comprehensive comparison of circulating tumor cells and breast imaging modalities as screening tools for breast cancer in Chinese women. Front Oncol 2022; 12:890248. [PMID: 35978805 PMCID: PMC9377692 DOI: 10.3389/fonc.2022.890248] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Accepted: 07/07/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Circulating tumor cells (CTCs) have been recognized as a sensitive biomarker for breast cancer (BC). This study aimed to comprehensively compare CTC with imaging modalities, including ultrasonography, mammography, and contrast-enhanced magnetic resonance imaging (MRI) in screening for BC in Chinese women. METHODS Three hundred forty-three participants were enrolled in this study, including 102 treatment-naive BC patients, 177 with breast benign diseases (BBD) and 64 healthy female patients. All participants underwent CTC testing and at least one of the following examinations, ultrasonography, mammography, and MRI at the Second Affiliated Hospital of Zhejiang University between December 2017 and November 2020. CTCs were quantitatively assessed using cell counting (CTC detection rate/counts) and categorically examined using a cutoff value (CTC classification). The diagnostic power of CTC tests and imaging modalities, including accuracy and capability to predict clinicopathological characteristics of BC, were evaluated and compared. RESULTS CTC classification with a cutoff value of 2 showed a "good" diagnostic accuracy of 0.889 for early- to mid-stage BC comparable to breast imaging modalities using Breast Imaging-Reporting and Data System (BI-RADS). MRI demonstrated the highest sensitivity of 0.872 for BC, and CTC classification had the highest specificity of 0.938. A relatively low sensitivity was found for mammography in this cohort of patients. Successful detection of BC by CTC detection rate/counts, but not CTC classification, correlated with two important clinicopathological features, American Joint Committee on Cancer (AJCC) stage and tumor-node-metastasis (TNM) stage. The detection power of certain imaging modalities was also associated with AJCC stage (ultrasonography, p = 0.0438 and MRI, p = 0.0422) and lymph node metastasis (ultrasonography, 0.0157). There were clear correlations between CTC tests (counts or classification) and imaging BI-RADS scoring system in detecting positive BC cases (p < 0.05). Further correlation analysis suggested that CTC quantity, but not CTC classification, had the capability to predict clinicopathological traits of BC that were identified by ultrasonography. CONCLUSIONS CTC tests have a diagnostic potency comparable to breast imaging modalities, and may be used as an alternative screening tool for BC.
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Affiliation(s)
- Xuan Shao
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
| | - Xiaoyan Jin
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
- Department of Surgical Oncology, Taizhou Municipal Hospital, Taizhou, China
| | - Zhigang Chen
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
| | - Zhigang Zhang
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
| | - Wuzhen Chen
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
| | - Jingxin Jiang
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
| | - Zhen Wang
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
| | - Ying Cui
- Hangzhou Watson Biotech, Hangzhou, China
| | | | - Ke Wang
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
| | - Xiuyan Yu
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
| | - Jian Huang
- Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou, China
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Meijer SE, Klebanov-Akopyn O, Pavlov V, Laks S, Hazzan D, Nissan A, Zippel D. Detection of Minimal Residual Disease in the Peripheral Blood of Breast Cancer Patients, with a Multi Marker (MGB-1, MGB-2, CK-19 and NY-BR-1) Assay. BREAST CANCER: TARGETS AND THERAPY 2021; 13:617-624. [PMID: 34815711 PMCID: PMC8605792 DOI: 10.2147/bctt.s337075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 11/04/2021] [Indexed: 11/23/2022]
Abstract
Purpose Minimal residual disease (MRD) refers to micrometastases that are undetectable by conventional means and is a potential source of disease relapse. This study aimed to detect the presence of breast cancer (BC) biomarkers (MGB-1, MGB-2, CK-19, NY-BR-1) using real-time polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMC) of BC patients and the impact of a positive assay on clinical outcome. Patients and Methods Patients in the analysis included females >18 years of age with biopsy-proven carcinoma of the breast. A 10 mL sample of venous blood was obtained from 10 healthy controls and 25 breast cancer patients. Comparisons of peripheral blood markers were made with clinicopathological variables. Results High-quality RNA was extracted from all samples with a mean RNA concentration of 224.8±155.3 ng/µL. Each of the molecular markers examined was highly expressed in the primary breast tumors (n = 3, positive controls) with none of the markers detected in healthy negative controls. The NY-BR-1 marker was expressed in one (4%) patient with metastatic disease with no MGB-1 and MGB-2 detected in any sample derived from the study patients. The CK-19 marker was detected in 16 (64%) of the BC cases. No correlation was found between CK-19 expression and tumor stage (P = 0.07) or nodal status (P = 0.32). No correlation was identified in the BC patients between CK-19 expression and receptor status in the BC primary tumor. Conclusion This study showed high expression of all 4 markers NY-BR-1, MGB-1, MGB-2 and CK-19 in the PBMCs derived from breast cancer patients. CK-19 was detected in 64% of the stage I–III cases operated with curative intent, the only recurrent events occurring in the CK-19-positive cases. Our data confirm the need to enhance techniques for detection of MRD, which may better predict patients at risk for relapse.
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Affiliation(s)
- Suzy E Meijer
- Department of Infectious Disease, Sourasky Medical Center, Tel Aviv, Israel
- The Surgical Oncology Laboratory, Hadassah-Hebrew University Hospital, Jerusalem, Israel
| | - Olga Klebanov-Akopyn
- The Surgical Oncology Laboratory, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Vera Pavlov
- The Surgical Oncology Laboratory, Hadassah-Hebrew University Hospital, Jerusalem, Israel
- The Surgical Oncology Laboratory, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Shachar Laks
- Department of General and Oncological Surgery – Surgery C, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - David Hazzan
- Department of General and Oncological Surgery – Surgery C, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Aviram Nissan
- The Surgical Oncology Laboratory, Hadassah-Hebrew University Hospital, Jerusalem, Israel
- The Surgical Oncology Laboratory, The Chaim Sheba Medical Center, Ramat Gan, Israel
- Department of General and Oncological Surgery – Surgery C, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Douglas Zippel
- The Surgical Oncology Laboratory, The Chaim Sheba Medical Center, Ramat Gan, Israel
- Department of General and Oncological Surgery – Surgery C, The Chaim Sheba Medical Center, Ramat Gan, Israel
- Correspondence: Douglas Zippel Department of General & Oncological Surgery-Surgery C, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, IsraelTel +972-3-530-2714Fax +972-3-5341562 Email
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Mäurer M, Pachmann K, Wendt T, Schott D, Wittig A. Prospective Monitoring of Circulating Epithelial Tumor Cells (CETC) Reveals Changes in Gene Expression during Adjuvant Radiotherapy of Breast Cancer Patients. ACTA ACUST UNITED AC 2021; 28:3507-3524. [PMID: 34590615 PMCID: PMC8482075 DOI: 10.3390/curroncol28050302] [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: 07/20/2021] [Revised: 08/22/2021] [Accepted: 09/03/2021] [Indexed: 11/27/2022]
Abstract
Circulating epithelial tumor cells (CETC) are considered to be responsible for the formation of metastases. Therefore, their importance as prognostic and/or predictive markers in breast cancer is being intensively investigated. Here, the reliability of single cell expression analyses in isolated and collected CETC from whole blood samples of patients with early-stage breast cancer before and after radiotherapy (RT) using the maintrac® method was investigated. Single-cell expression analyses were performed with qRT-PCR on a panel of selected genes: GAPDH, EpCAM, NANOG, Bcl-2, TLR 4, COX-2, PIK3CA, Her-2/neu, Vimentin, c-Met, Ki-67. In all patients, viable CETC were detected prior to and at the end of radiotherapy. In 7 of the 9 (77.8%) subjects examined, the CETC number at the end of the radiotherapy series was higher than before. The majority of genes analyzed showed increased expression after completion of radiotherapy compared to baseline. Procedures and methods used in this pilot study proved to be feasible. The method is suitable for further investigation of the underlying molecular biological mechanisms occurring in cells surviving radiotherapy and possibly the development of radiation resistance.
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Affiliation(s)
- Matthias Mäurer
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743 Jena, Germany; (T.W.); (A.W.)
- Correspondence:
| | - Katharina Pachmann
- Transfusion Center Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany; (K.P.); (D.S.)
| | - Thomas Wendt
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743 Jena, Germany; (T.W.); (A.W.)
| | - Dorothea Schott
- Transfusion Center Bayreuth, Kurpromenade 2, 95448 Bayreuth, Germany; (K.P.); (D.S.)
| | - Andrea Wittig
- Department of Radiotherapy and Radiation Oncology, University Hospital Jena, Bachstraße 18, 07743 Jena, Germany; (T.W.); (A.W.)
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The Alterations and Potential Roles of MCMs in Breast Cancer. JOURNAL OF ONCOLOGY 2021; 2021:7928937. [PMID: 34475953 PMCID: PMC8407980 DOI: 10.1155/2021/7928937] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 07/07/2021] [Accepted: 08/04/2021] [Indexed: 12/11/2022]
Abstract
The minichromosome maintenance (MCM) protein family plays a key role in eukaryotic DNA replication and has been confirmed to be associated with the occurrence and progression of many tumors. However, the expression levels, functions, and prognostic values of MCMs in breast cancer (BC) have not been clearly and systematically explained. In this article, we studied the transcriptional levels of MCMs in BC based on the Oncomine database. Kaplan-Meier plotter was used to analyze prognostic value of MCMs in human BC patients. Furthermore, we constructed a MCM coexpression gene network and performed functional annotation analysis through DAVID to reveal the functions of MCMs and coexpressed genes. The data showed that the expression of MCM2–8 and MCM10 but not MCM1 and MCM9 was upregulated in BC. Kaplan-Meier plotter analysis revealed that high transcriptional levels of MCM2, MCM4–7, and MCM10 were significantly related to low relapse-free survival (RFS) in BC patients. In contrast, high levels of MCM1 and MCM9 predicted high RFS for BC patients. This study suggests that MCM2, MCM4–7, and MCM10 possess great potential to be valuable prognostic biomarkers for BC and that MCM1 and MCM9 may serve as potential treatment targets for BC patients.
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Kryvoshlyk I. CIRCULATING TUMOR CELLS: WHERE WE LEFT OFF? BIOTECHNOLOGIA ACTA 2021. [DOI: 10.15407/biotech14.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Cancer metastasis and recurrence are the leading causes of cancer-related death. Tumor cells which leave the primary or secondary tumors and shed into the bloodstream are called circulating tumor cells (CTC). These cells are the key drivers of cancer dissemination to surrounding tissues and to distant organs. The use of CTC in clinical practice necessitates the deep insight into their biology, as well as into their role in cancer evasion of immune surveillance, tumor resistance to chemo- radio- and immunotherapies and metastatic dormancy. Aim. The purpose of the work was to review the current knowledge on the CTC biology, as well as the prospects for their use for the diagnosis and targeted treatment of metastatic disease. Methods. The work proposed the integrative literature review using MEDLINE, Biological Abstracts and EMBASE databases. Results. This review summarizes and discusses historical milestones and current data concerning СTС biology, the main stages of their life cycle, their role in metastatic cascade, clinical prospects for their use as markers for the diagnosis and prognostication of the disease course, as well as targets for cancer treatment. Conclusions. Significant progress in the area of CTC biology and their use in cancer theranostics convincingly proved the attractiveness of these cells as targets for cancer prognosis and therapy. The effective use of liquid biopsy with quantitative and phenotypic characteristics of CTCs is impeded by the imperfection of the methodology for taking biological material and by the lack of reliable markers for assessing the metastatic potential of CTCs of various origins. The variety of mechanisms of tumor cells migration and invasion requires the development of complex therapeutic approaches for anti-metastatic therapy targeting CTCs. Efforts to address these key issues could help developing new and effective cancer treatment strategies.
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Coleman R. Bisphosphonates and breast cancer - From cautious palliation to saving lives. Bone 2020; 140:115570. [PMID: 32745688 DOI: 10.1016/j.bone.2020.115570] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 07/13/2020] [Accepted: 07/28/2020] [Indexed: 01/11/2023]
Abstract
Bone metastases are common in breast cancer and may cause considerable morbidity including fractures, severe pain, nerve compression and hypercalcaemia. Alongside developments in the multidisciplinary management for patients with metastatic breast cancer, the use of bisphosphonates, and more recently denosumab, has transformed the course of advanced breast cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Additionally, because the bone marrow microenvironment is so intimately involved in the metastatic processes required for cancer dissemination, the use of adjuvant bisphosphonates has been studied extensively over the past 25 years in many randomised trials. We now have clear evidence that bisphosphonates significantly reduce both metastasis to bone and mortality in postmenopausal women with early breast cancer. Efficacy seems similar across different biological subgroups of postmenopausal breast cancer with the use of either a nitrogen-containing bisphosphonate such as intravenous zoledronate or daily oral ibandronate as well as the non-nitrogen containing agent, daily oral clodronate. In this overview of evolving role of bisphosphonates in breast cancer, focussing particularly on pamidronate and zoledronate, the long winding development road from the 1970s through to the present day is described and some of the serendipitous findings, "lucky breaks" and regulatory decisions along the way outlined.
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Affiliation(s)
- Robert Coleman
- Mellanby Centre for Bone Research, Department of Oncology and Metabolism, University of Sheffield, United Kingdom.
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