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Zhou Y, Li P, Yao S, Kong W. Endoscopic Rectal Ultrasound-Based Radiomics Analysis for the Prediction of Synchronous Liver Metastasis in Patients With Primary Rectal Cancer. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2025; 44:359. [PMID: 39392061 DOI: 10.1002/jum.16601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 09/23/2024] [Indexed: 10/12/2024]
Affiliation(s)
- Ying Zhou
- Tianjin Medical University, Tianjin, China
| | - Peifeng Li
- Tianjin Medical University, Tianjin, China
| | | | - Weina Kong
- Tianjin Medical University, Tianjin, China
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Vitale F, Zileri Dal Verme L, Paratore M, Negri M, Nista EC, Ainora ME, Esposto G, Mignini I, Borriello R, Galasso L, Alfieri S, Gasbarrini A, Zocco MA, Nicoletti A. The Past, Present, and Future of Biomarkers for the Early Diagnosis of Pancreatic Cancer. Biomedicines 2024; 12:2840. [PMID: 39767746 PMCID: PMC11673965 DOI: 10.3390/biomedicines12122840] [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: 11/01/2024] [Revised: 11/30/2024] [Accepted: 12/11/2024] [Indexed: 01/04/2025] Open
Abstract
Pancreatic cancer is one of the most aggressive cancers with a very poor 5-year survival rate and reduced therapeutic options when diagnosed in an advanced stage. The dismal prognosis of pancreatic cancer has guided significant efforts to discover novel biomarkers in order to anticipate diagnosis, increasing the population of patients who can benefit from curative surgical treatment. CA 19-9 is the reference biomarker that supports the diagnosis and guides the response to treatments. However, it has significant limitations, a low specificity, and is inefficient as a screening tool. Several potential biomarkers have been discovered in the serum, urine, feces, and pancreatic juice of patients. However, most of this evidence needs further validation in larger cohorts. The advent of advanced omics sciences and liquid biopsy techniques has further enhanced this field of research. The aim of this review is to analyze the historical evolution of the research on novel biomarkers for the early diagnosis of pancreatic cancer, focusing on the current evidence for the most promising biomarkers from different body fluids and the novel trends in research, such as omics sciences and liquid biopsy, in order to favor the application of modern personalized medicine.
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Affiliation(s)
- Federica Vitale
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Lorenzo Zileri Dal Verme
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Mattia Paratore
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Marcantonio Negri
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Enrico Celestino Nista
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Maria Elena Ainora
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Giorgio Esposto
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Irene Mignini
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Raffaele Borriello
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Linda Galasso
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Sergio Alfieri
- Centro Pancreas, Chirurgia Digestiva, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy;
| | - Antonio Gasbarrini
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Maria Assunta Zocco
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
| | - Alberto Nicoletti
- CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy; (F.V.); (L.Z.D.V.); (M.P.); (M.N.); (E.C.N.); (M.E.A.); (G.E.); (I.M.); (R.B.); (L.G.); (A.G.); (A.N.)
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Sanchez-Mendez J, Quino JE, Xiong W, Stern MC. Colorectal cancer outcomes among Hispanic/Latino patients in the United States: a scoping review protocol. JBI Evid Synth 2024; 22:1347-1354. [PMID: 38745480 PMCID: PMC11236500 DOI: 10.11124/jbies-23-00296] [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] [Indexed: 05/16/2024]
Abstract
OBJECTIVE This scoping review will identify the patterns of survival, treatment, and recurrence among Hispanic and/or Latino/a/x (H/L) patients with colorectal cancer (CRC) living in the United States (US) and Puerto Rico. Additionally, population- and individual-level determinants of cancer outcomes among H/L CRC patients will be mapped to highlight under-reported/under-investigated research areas. INTRODUCTION CRC is the third most common cancer excluding skin cancers in the US. Unlike non-Hispanic White populations, cancer is the number one cause of death in H/L populations and currently represents 21% of total deaths. Despite this, a lack of consensus exists on CRC outcomes for H/L patients. Most research on H/L individuals has examined incidence and screening of CRC, with fewer studies focusing on cancer outcomes. INCLUSION CRITERIA All epidemiological study designs and systematic reviews will be considered. The review will only include peer-reviewed studies that report on survival, treatment, and/or recurrence patterns for H/L patients with CRC residing in the US and Puerto Rico. METHODS A 3-step search with a 2-stage study selection process will be followed, as recommended by JBI and Arksey and O'Malley. Databases to be searched will include MEDLINE (PubMed), Embase (Ovid), and Scopus. A data extraction tool will be designed based on JBI recommendations. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRSIMA-ScR) will be used, with the results presented in a PRISMA diagram. Publications in English from database inception to the present will be considered. REVIEW REGISTRATION Open Science Framework https://osf.io/y6qf5.
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Affiliation(s)
- Joel Sanchez-Mendez
- Department of Population and Public Health Sciences, Keck School of Medicine of University of Southern California, University of Southern California, CA, USA
| | - Juanita Elizabeth Quino
- Department of Population and Public Health Sciences, Keck School of Medicine of University of Southern California, University of Southern California, CA, USA
| | - Wei Xiong
- Department of Population and Public Health Sciences, Keck School of Medicine of University of Southern California, University of Southern California, CA, USA
| | - Mariana C. Stern
- Department of Population and Public Health Sciences, Keck School of Medicine of University of Southern California, University of Southern California, CA, USA
- Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, University of Southern California, CA, USA
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Hoseini SH, Enayati P, Nazari M, Babakhanzadeh E, Rastgoo M, Sohrabi NB. Biomarker Profile of Colorectal Cancer: Current Findings and Future Perspective. J Gastrointest Cancer 2024; 55:497-510. [PMID: 38168859 DOI: 10.1007/s12029-023-00990-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2023] [Indexed: 01/05/2024]
Abstract
OBJECTIVE Breakthroughs in omics technology have led to a deeper understanding of the fundamental molecular changes that play a critical role in the development and progression of cancer. This review delves into the hidden molecular drivers of colorectal cancer (CRC), offering potential for clinical translation through novel biomarkers and personalized therapies. METHODS We summarizes recent studies utilizing various omics approaches, including genomics, transcriptomics, proteomics, epigenomics, metabolomics and data integration with computational algorithms, to investigate CRC. RESULTS Integrating multi-omics data in colorectal cancer research unlocks hidden biological insights, revealing new pathways and mechanisms. This powerful approach not only identifies potential biomarkers for personalized prognosis, diagnosis, and treatment, but also predicts patient response to specific therapies, while computational tools illuminate the landscape by deciphering complex datasets. CONCLUSIONS Future research should prioritize validating promising biomarkers and seamlessly translating them into clinical practice, ultimately propelling personalized CRC management to new heights.
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Affiliation(s)
| | - Parisa Enayati
- Biological Sciences Department, Northern Illinois University, DeKalb, IL, USA
| | - Majid Nazari
- Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
- , P.O. Box, Tehran, 64155-65117, Iran.
| | - Emad Babakhanzadeh
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Rastgoo
- Department of Microbiology, Shiraz Islamic Azad University, Shiraz, Iran
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Wang K, Ma L, Chen L, Jiang Y, Liu N, Cai J, Zhang Y. The clinical value of a nomogram constructed from CEA, CA199, PT, FIB, tumor differentiation and TNM stage in colorectal cancer. Cancer Biomark 2023; 38:537-549. [PMID: 37980649 DOI: 10.3233/cbm-230116] [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] [Indexed: 11/21/2023]
Abstract
BACKGROUND The accurate Tumor-Node-Metastasis (TNM) staging of colorectal cancer (CRC) is of great guiding significance for the judgment of tumor progression and prognosis, and the formulation of treatment strategies. OBJECTIVE The aim of this study was to construct a recurrence risk scoring (RRS) system and prognostic prediction model to improve the accuracy of staging, prognosis prediction, and clinical decision making in resectable CRC. METHODS CRC patients who underwent radical resection were retrospectively enrolled into study. Multivariable Cox regression model was applied to screen for independent prognostic factors. The RRS system is composed of independent prognostic factors which was awarded 1point each. A prognostic model composed of RRS and TNM staging system (RRS-TNM model) was applied to predict postoperative recurrence. RESULTS TNM stage, tumor differentiation, preoperative elevated Carcinoembryonic Antigen, Carbohydrate Antigen 199, Prothrombin Time and Fibrinogen were the independent prognostic biomarkers. 173 of 540 patients had recurrence. The 5-year cumulative recurrence rate (5-y CRR) and disease-free survival (DFS) of postoperative p-TNM stage I, II, and III were 12.7% and 104.8 months, 26.5% and 89.3 months, and 55.5% and 57.3 months, respectively. The 5-y CRR and DFS of preoperative Low-risk (RRS 0-1score), Middle-risk (RRS 2-3scores), and High-risk (RRS 4-5scores) groups were 13.9% and 101.1 months, 40.9% and 75.5 months, and 70.2% and 41.1 months. The AUC (area under ROC curve) of RRS system was not inferior to that of TNM staging system (0.713 vs. 0.666; P= 0.093). The AUC (0.770) and C-index value (0.721) of RRS-TNM model were significantly better than both RRS and TNM staging system (P< 0.001). CONCLUSIONS The RRS system accurately identifies CRC patients with high-risk recurrence preoperatively. Constructing a nomogram using the RRS system and TNM staging significantly improves the accuracy of staging and prognosis prediction, which is of great clinical significance for individualized clinical treatment and follow-up of CRC.
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Affiliation(s)
- Kang Wang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Lulu Ma
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Liying Chen
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Yatong Jiang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Ningquan Liu
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Jianchun Cai
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
| | - Yiyao Zhang
- Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
- Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, Fujian, China
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Alorda-Clara M, Torrens-Mas M, Morla-Barcelo PM, Martinez-Bernabe T, Sastre-Serra J, Roca P, Pons DG, Oliver J, Reyes J. Use of Omics Technologies for the Detection of Colorectal Cancer Biomarkers. Cancers (Basel) 2022; 14:817. [PMID: 35159084 PMCID: PMC8834235 DOI: 10.3390/cancers14030817] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/31/2022] [Accepted: 02/04/2022] [Indexed: 12/14/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers with high mortality rates, especially when detected at later stages. Early detection of CRC can substantially raise the 5-year survival rate of patients, and different efforts are being put into developing enhanced CRC screening programs. Currently, the faecal immunochemical test with a follow-up colonoscopy is being implemented for CRC screening. However, there is still a medical need to describe biomarkers that help with CRC detection and monitor CRC patients. The use of omics techniques holds promise to detect new biomarkers for CRC. In this review, we discuss the use of omics in different types of samples, including breath, urine, stool, blood, bowel lavage fluid, or tumour tissue, and highlight some of the biomarkers that have been recently described with omics data. Finally, we also review the use of extracellular vesicles as an improved and promising instrument for biomarker detection.
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Affiliation(s)
- Marina Alorda-Clara
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
| | - Margalida Torrens-Mas
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Translational Research in Aging and Longevity (TRIAL) Group, Instituto de Investigación Sanitaria Illes Balears (IdISBa), E-07120 Palma de Mallorca, Illes Balears, Spain
| | - Pere Miquel Morla-Barcelo
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
| | - Toni Martinez-Bernabe
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
| | - Jorge Sastre-Serra
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Ciber Fisiopatología Obesidad y Nutrición (CB06/03) Instituto Salud Carlos III, E-28029 Madrid, Madrid, Spain
| | - Pilar Roca
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Ciber Fisiopatología Obesidad y Nutrición (CB06/03) Instituto Salud Carlos III, E-28029 Madrid, Madrid, Spain
| | - Daniel Gabriel Pons
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
| | - Jordi Oliver
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Ciber Fisiopatología Obesidad y Nutrición (CB06/03) Instituto Salud Carlos III, E-28029 Madrid, Madrid, Spain
| | - Jose Reyes
- Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, E-07122 Palma de Mallorca, Illes Balears, Spain; (M.A.-C.); (M.T.-M.); (P.M.M.-B.); (T.M.-B.); (J.S.-S.); (P.R.); (D.G.P.)
- Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Edificio S, E-07120 Palma de Mallorca, Illes Balears, Spain
- Servicio Aparato Digestivo, Hospital Comarcal de Inca, E-07300 Inca, Illes Balears, Spain
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Lead Time and Prognostic Role of Serum CEA, CA19-9, IL-6, CRP, and YKL-40 after Adjuvant Chemotherapy in Colorectal Cancer. Cancers (Basel) 2021; 13:cancers13153892. [PMID: 34359796 PMCID: PMC8345682 DOI: 10.3390/cancers13153892] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/23/2021] [Accepted: 07/26/2021] [Indexed: 12/24/2022] Open
Abstract
In colorectal cancer (CRC), 20-50% of patients relapse after curative-intent surgery with or without adjuvant therapy. We investigated the lead times and prognostic value of post-adjuvant (8 months from randomisation to adjuvant treatment) serum CEA, CA19-9, IL-6, CRP, and YKL-40. We included 147 radically resected stage II-IV CRC treated with 24 weeks of adjuvant 5-fluorouracil-based chemotherapy in the phase III LIPSYT-study (ISRCTN98405441). All 147 were included in lead time analysis, but 12 relapsing during adjuvant therapy were excluded from post-adjuvant analysis. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired disease-free survival (DFS) with hazard ratio (HR) 5.21 (95% confidence interval 2.32-11.69); 3.72 (1.99-6.95); 2.58 (1.18-5.61), respectively, and elevated IL-6 and CRP with impaired overall survival (OS) HR 3.06 (1.64-5.73); 3.41 (1.55-7.49), respectively. Elevated post-adjuvant IL-6 in CEA-normal patients identified a subgroup with impaired DFS. HR 3.12 (1.38-7.04) and OS, HR 3.20 (1.39-7.37). The lead times between the elevated biomarker and radiological relapse were 7.8 months for CEA and 10.0-53.1 months for CA19-9, IL-6, CRP, and YKL-40, and the lead time for the five combined was 27.3 months. Elevated post-adjuvant CEA, IL-6, and CRP were associated with impaired DFS. The lead time was shortest for CEA.
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O'Neill RS, Stoita A. Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket? World J Gastroenterol 2021; 27:4045-4087. [PMID: 34326612 PMCID: PMC8311531 DOI: 10.3748/wjg.v27.i26.4045] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/24/2021] [Accepted: 06/15/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis. To combat this, there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma. Currently, serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker. In the search for a biomarker that is both sensitive and specific for the diagnosis of PC, there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC. Currently, promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA (miRNA) in serum and circulating tumour cells. Both these modalities, although in their infancy and yet to be widely accepted into routine clinical practice, possess merit in the early detection of PC. We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC (serum, urinary, salivary, faecal, pancreatic juice and biliary fluid).
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Affiliation(s)
- Robert S O'Neill
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney 2010, Australia
- St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
| | - Alina Stoita
- Department of Gastroenterology, St Vincent's Hospital Sydney, Sydney 2010, Australia
- St Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney 2010, Australia
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Uludag SS, Sanli AN, Zengin AK, Ozcelik MF. Systemic Inflammatory Biomarkers as Surrogate Markers for Stage in Colon Cancer. Am Surg 2021; 88:1256-1262. [PMID: 33596111 DOI: 10.1177/0003134821995059] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND This study aimed to investigate whether the systemic inflammatory parameters currently in use in staging the disease can be used as biomarker tests operated colon cancer patients. Neutrophil, lymphocyte, monocyte, platelet, neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), neutrophil/monocyte ratio (NMR), CRP, albumin, lymphocyte/CRP ratio, CRP/albumin ratio, and neutrophil/albumin ratio as systemic inflammatory biomarkers and prognostic nutritional index (PNI) were evaluated. METHODS This retrospective study included 592 patients. Patients with colon cancer in the cohort were divided into 2 subgroups: Tumor, nodes, metastases (TNM) stage 0, TNM stage 1, and TNM stage 2; early stage (n: 332) and TNM stage 3 and TNM stage 4; late stage (n: 260) colon cancer patients. RESULTS LDH (P < .001), NLR (P < .001), PLR (P < .05), CRP/albumin (P < .01), and neutrophil/albumin (P < .01) were significantly higher, while monocyte count (P < .05) and PNI (P < .01) were found to be significantly lower in late stage colon cancer patients than in early stage colon cancer patients. Moderate negative correlation was found between the PNI and the neutrophil/albumin ratio in late stage colon cancer patients (r: -.568, P < .001). CONCLUSIONS Our data suggest that high serum LDH, NLR, PLR, CRP/albumin, and neutrophil/albumin may be useful predictive markers for advanced stage in colon cancer. According to the receiver operating characteristic analysis results, CRP/albumin ratio can be used to discriminate early from late stage. Preoperative low monocyte count and PNI are associated with postoperative staging patients with colon cancer.
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Affiliation(s)
- Server Sezgin Uludag
- Department of Surgery, Cerrahpasa Medicine Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ahmet Necati Sanli
- Department of Surgery, Cerrahpasa Medicine Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Abdullah Kagan Zengin
- Department of Surgery, Cerrahpasa Medicine Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Mehmet Faik Ozcelik
- Department of Surgery, Cerrahpasa Medicine Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
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The Elevated Pre-Treatment C-Reactive Protein Predicts Poor Prognosis in Patients with Locally Advanced Rectal Cancer Treated with Neo-Adjuvant Radiochemotherapy. Diagnostics (Basel) 2020; 10:diagnostics10100780. [PMID: 33023215 PMCID: PMC7601888 DOI: 10.3390/diagnostics10100780] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/21/2020] [Accepted: 09/30/2020] [Indexed: 01/08/2023] Open
Abstract
The aim of the present study was to investigate the association of the pre-treatment C-reactive protein (CRP) plasma level with survival outcomes in a cohort of 423 consecutive patients with locally advanced rectal cancer treated with neo-adjuvant radiochemotherapy followed by surgical resection. To evaluate the prognostic value of the CRP level for clinical endpoints recurrence-free survival (RFS), local-regional control (LC), metastases-free survival (MFS), and overall survival (OS), uni- and multivariate Cox regression analyses were applied, and survival rates were calculated using Kaplan–Meier analysis. The median follow-up time was 73 months. In univariate analyses, the pre-treatment CRP level was a significant predictor of RFS (hazard ratio (HR) 1.015, 95% CI 1.006–1.023; p < 0.001), LC (HR 1.015, 95% CI 1.004–1.027; p = 0.009), MFS (HR 1.014, 95% CI 1.004–1.023; p = 0.004), and OS (HR 1.016, 95% CI 1.007–1.024; p < 0.001). Additionally, univariate analysis identified the MRI circumferential resection margin (mrCRM) and pre-treatment carcinoembryonic antigen (CEA) as significant predictor of RFS (HR 2.082, 95% CI 1.106–3.919; p = 0.023 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). Univariate analysis also revealed a significant association of the mrCRM (HR 2.089, 95% CI 1.052–4.147; p = 0.035) and CEA (HR 1.006, 95% CI 1.003–1.008; p < 0.001) with MFS. Age and CEA were prognostic factors for OS (HR 1.039, 95% CI 1.013–1.066; p = 0.003 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). In multivariate analysis that included parameters with a p-level < 0.20 in univariate analysis, the pre-treatment CRP remained a significant prognostic factor for RFS (HR 1.013, 95%CI 1.001–1.025; p = 0.036), LC (HR 1.014, 95% CI 1.001–1.027; p = 0.031), and MFS (HR 1.013, 95% CI 1.000–1.027; p = 0.046). The results support the hypothesis that an elevated pre-treatment CRP level is a predictor of poor outcome. If confirmed by additional studies, this easily measurable biomarker could contribute to the identification of patients who might be candidates for more aggressive local or systemic treatment approaches or the administration of anti-inflammatory drugs.
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Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development. Molecules 2020; 25:molecules25030619. [PMID: 32023884 PMCID: PMC7036866 DOI: 10.3390/molecules25030619] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 01/24/2020] [Accepted: 01/28/2020] [Indexed: 02/07/2023] Open
Abstract
Background: Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166 proteins for patients in stages I–II and III–IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (p < 0.01) for distinguishing stages I–II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.
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Peng Z, Duan F, Yin J, Feng Y, Yang Z, Shang J. Prognostic values of microRNA-130 family expression in patients with cancer: a meta-analysis and database test. J Transl Med 2019; 17:347. [PMID: 31640738 PMCID: PMC6805372 DOI: 10.1186/s12967-019-2093-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 10/11/2019] [Indexed: 02/19/2023] Open
Abstract
BACKGROUND Emerging evidence shows that microRNA-130 (miRNA-130) family may be useful as prognostic biomarkers in cancer. However, there is no confirmation in an independent validation study. The aim of this study was to summarize the prognostic value of miRNA-130 family (miRNA-130a and miRNA-130b) for survival in patients with cancer. METHODS The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the association strength between miRNA-130 family expression and prognosis. Kaplan-Meier plotters were used to verify the miRNA-130b expression and overall survival (OS). RESULTS A total of 2141 patients with OS and 1159 patients with disease-free survival (DFS)/progression-free survival (PFS) were analyzed in evidence synthesis. For the miRNA-130a, the overall pooled effect size (HR) was HR 1.58 (95% CI: 1.21-2.06, P < 0.001). Tissue and serum expression of miRNA-130a was significantly associated with the OS (HR = 1.54, 95% CI: 1.11-2.14, P = 0.009; HR = 1.65, 95% CI: 1.14-2.38, P = 0.008), and in gastric cancer (HR = 1.81, 95% CI: 1.34-2.45, P < 0.001). For the miRNA-13b, a statistical correlation was observed between high miRNA-130b expression and poor OS in patients with cancer (HR = 1.95, 95% CI: 1.47-2.59, P < 0.001), especially in tissue sample (HR = 2.01, 95% CI: 1.39-2.91, P < 0.001), Asian (HR = 2.55, 95% Cl: 1.77-3.69, P < 0.001) and hepatocellular carcinoma (HR = 1.87, 95% CI: 1.23-2.85, P = 0.004). The expression of miRNA-130b was significantly correlated with DFS/PFS (HR = 1.53, 95% CI: 1.31-1.77, P < 0.001), in tissue (HR = 1.98, 95% CI: 1.50-2.62, P < 0.001) and serum (HR = 1.37, 95% CI: 1.15-1.64, P < 0.001), especially in HCC (HR = 1.98, 95% CI: 1.50, 2.62, P < 0.001). In database test, a significant correlation between high miRNA-130b expression and poor OS for HCC patients was observed (HR = 1.55, 95% CI: 1.01, 2.35, P = 0.0045). CONCLUSION The high expression of miRNA-130 family might predict poor prognosis in cancer patients. Prospectively, combining miRNA-130a and miRNA-130b may be considered as powerful prognostic predictor for clinical application.
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Affiliation(s)
- Zhen Peng
- Department of Infectious Disease, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China.
| | - Fujiao Duan
- Medical Research Office, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China.
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
| | - Jingjing Yin
- College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
| | - Yajing Feng
- Department of Nosocomial Infection Management, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhongyu Yang
- College of Art and Science, The Ohio State University, Columbus, OH, USA
| | - Jia Shang
- Department of Infectious Disease, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
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Lee Y, Kim SS, Lee JH. Chemiluminescent dual-enzyme immunoassays capable of simultaneously quantifying carbohydrate antigen 19–9 and carcinoma embryonic antigen in a sample. Anal Chim Acta 2019; 1060:88-96. [DOI: 10.1016/j.aca.2019.01.048] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/21/2018] [Accepted: 01/23/2019] [Indexed: 12/22/2022]
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Bedin C, Crotti S, D'Angelo E, D'Aronco S, Pucciarelli S, Agostini M. Circulating Biomarkers for Response Prediction of Rectal Cancer to Neoadjuvant Chemoradiotherapy. Curr Med Chem 2019; 27:4274-4294. [PMID: 31060482 DOI: 10.2174/0929867326666190507084839] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 03/05/2019] [Accepted: 04/18/2019] [Indexed: 12/20/2022]
Abstract
Rectal cancer response to neoadjuvant Chemoradiotherapy (pCRT) is highly variable. In fact, it has been estimated that only about 21 % of patients show pathologic Complete Response (pCR) after therapy, while in most of the patients a partial or incomplete tumour regression is observed. Consequently, patients with a priori chemoradioresistant tumour should not receive the treatment, which is associated with substantial adverse effects and does not guarantee any clinical benefit. For Locally Advanced Rectal Cancer Patients (LARC), a standardized neoadjuvant treatment protocol is applied, the identification and the usefulness of prognostic or predictive biomarkers can improve the antitumoural treatment strategy, modifying the sequence, dose, and combination of radiotherapy, chemotherapy and surgical resection. For these reasons, a growing number of studies are actually focussed on the discovery and investigation of new predictive biomarkers of response to pCRT. In this review, we have selected the most recent literature (2012-2017) regarding the employment of blood-based biomarkers potentially predicting pCR in LARC patients and we have critically discussed them to highlight their real clinical benefit and the current limitations of the proposed methodological approaches.
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Affiliation(s)
- Chiara Bedin
- Nano-inspired Biomedicine Lab, Paediatric Research Institute-Città della Speranza, Padua, Italy
| | - Sara Crotti
- Nano-inspired Biomedicine Lab, Paediatric Research Institute-Città della Speranza, Padua, Italy
| | - Edoardo D'Angelo
- Nano-inspired Biomedicine Lab, Paediatric Research Institute-Città della Speranza, Padua, Italy
| | - Sara D'Aronco
- Nano-inspired Biomedicine Lab, Paediatric Research Institute-Città della Speranza, Padua, Italy,First Surgical Clinic Section, Department of Surgical, Oncological and Gastroenterological Science, University of
Padua, Padua, Italy
| | - Salvatore Pucciarelli
- First Surgical Clinic Section, Department of Surgical, Oncological and Gastroenterological Science, University of
Padua, Padua, Italy
| | - Marco Agostini
- Nano-inspired Biomedicine Lab, Paediatric Research Institute-Città della Speranza, Padua, Italy,First Surgical Clinic Section, Department of Surgical, Oncological and Gastroenterological Science, University of
Padua, Padua, Italy
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Abstract
Unexplained iron-deficiency anemia is an important marker for colorectal cancer (CRC). Our objectives were as follows: (a) to assess whether the association between anemia and CRC can be detected on the 'Clinical Practice Research Datalink', (b) to evaluate the timing between laboratory changes and CRC detection, and (c) to analyze its association with survival. We conducted a case-control study on patients with an incident CRC diagnosis during 2008-2012 and a 1 : 1-matched control group. We compared anemia markers serum ferritin (SF), hemoglobin (Hb), mean corpuscular volume (MCV), and red blood cell count between cases and controls using conditional logistic regression. We assessed survival in CRC cases. SF values up to 20 ng/ml were associated with an odds ratio [OR (95% confidence interval)] of 10.66 (6.88-16.51) compared with SF values of 101-300 ng/ml when restricted to measurements up to 180 days before the CRC diagnosis. For measurements taken at 1 year or earlier before the diagnosis, the OR was 2.02 (1.57-2.61). For Hb values less than 9 g/dl compared with Hb values of 13.0-15.9 g/dl the corresponding ORs were 74.25 (34.69-158.91) and 2.19 (1.31-3.67), respectively. The corresponding ORs for MCV values up to 80 fl compared with MCV values of 86-95 fl were 13.94 (10.31-18.85) and 1.89 (1.51-2.36), respectively. Low levels of these markers were only weakly associated with survival. Hb, MCV, and SF levels substantially dropped only shortly before the CRC diagnosis. Although slightly more cases had anemia markers compared with controls at 1 year or earlier before the diagnosis, most cases still had normal values. The Clinical Practice Research Datalink is well-suited to detect associations between low Hb, MCV, and SF levels and CRC.
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Brichacek AL, Brown CM. Alkaline phosphatase: a potential biomarker for stroke and implications for treatment. Metab Brain Dis 2019; 34:3-19. [PMID: 30284677 PMCID: PMC6351214 DOI: 10.1007/s11011-018-0322-3] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2018] [Accepted: 09/24/2018] [Indexed: 12/14/2022]
Abstract
Stroke is the fifth leading cause of death in the U.S., with more than 100,000 deaths annually. There are a multitude of risks associated with stroke, including aging, cardiovascular disease, hypertension, Alzheimer's disease (AD), and immune suppression. One of the many challenges, which has so far proven to be unsuccessful, is the identification of a cost-effective diagnostic or prognostic biomarker for stroke. Alkaline phosphatase (AP), an enzyme first discovered in the 1920s, has been evaluated as a potential biomarker in many disorders, including many of the co-morbidities associated with stroke. This review will examine the basic biology of AP, and its most common isoenzyme, tissue nonspecific alkaline phosphatase (TNAP), with a specific focus on the central nervous system. It examines the preclinical and clinical evidence which supports a potential role for AP in stroke and suggests potential mechanism(s) of action for AP isoenzymes in stroke. Lastly, the review speculates on the clinical utility of AP isoenzymes as potential blood biomarkers for stroke or as AP-targeted treatments for stroke patients.
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Affiliation(s)
- Allison L Brichacek
- Department of Microbiology, Immunology, and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9177, Morgantown, WV, 26506, USA
- Department of Neuroscience, Emergency Medicine, and Microbiology, Immunology and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9303, Morgantown, WV, 26506, USA
| | - Candice M Brown
- Department of Microbiology, Immunology, and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9177, Morgantown, WV, 26506, USA.
- Department of Neuroscience, Emergency Medicine, and Microbiology, Immunology and Cell Biology, Center for Basic and Translational Stroke Research, WVU Rockefeller Neuroscience Institute, West Virginia University School of Medicine, Box 9303, Morgantown, WV, 26506, USA.
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Lin HY, Tan GQ, Liu Y, Lin SQ. The prognostic value of serum amyloid A in solid tumors: a meta-analysis. Cancer Cell Int 2019; 19:62. [PMID: 30930691 PMCID: PMC6425599 DOI: 10.1186/s12935-019-0783-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Accepted: 03/15/2019] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Previous studies have demonstrated that serum amyloid A (SAA) levels are correlated with the clinical outcomes of solid tumors. However, the available data have not been systematically evaluated. The objective of the present meta-analysis was to explore the prognostic value of SAA levels in solid tumors. METHODS Eligible studies were identified from the PubMed, EMBASE and Science Citation Index electronic databases. The clinical characteristics, disease/progression-free survival (DFS/PFS) and overall survival (OS) were extracted from the eligible studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Stata 12.0 software. We also performed subgroup, meta-regression and sensitivity analyses. RESULTS In total, 12 eligible studies including 2749 patients were enrolled in the present meta-analysis. The pooled HRs with 95% CIs showed that elevated levels of SAA were significantly associated with poor OS (HR = 3.01, 95% CI 1.96-4.63) and DFS/PFS (HR = 1.67, 95% CI 1.31-2.12) in patients with solid tumors. Although publication bias was seem found in the studies with regard to OS, a further trim and fill analysis revealed that the adjusted HR was 3.02 (95% CI 1.96-4.63), which was close to the original HR. Subgroup analysis confirmed an elevated level of SAA as a strong prognostic marker in patients with solid tumors, regardless of tumor type, detection method, cut-off value, sample size, area and variance analyses. CONCLUSION Our meta-analysis indicated that elevated levels of SAA might be an unfavorable prognostic marker for OS in patients with solid tumors.
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Affiliation(s)
- Hai-yingjie Lin
- Department of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630 Guangdong China
| | - Guo-qiang Tan
- Department of Oncology, Jiangmen Central Hospital, Jiangmen, 529030 Guangdong China
| | - Yan Liu
- Department of Oncology, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, 442008 Hubei China
| | - Shao-qiang Lin
- Clinical Department of Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080 Guangdong China
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Schellerer VS, Langheinrich MC, Zver V, Grützmann R, Stürzl M, Gefeller O, Naschberger E, Merkel S. Soluble intercellular adhesion molecule-1 is a prognostic marker in colorectal carcinoma. Int J Colorectal Dis 2019; 34:309-317. [PMID: 30470940 PMCID: PMC6331741 DOI: 10.1007/s00384-018-3198-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/12/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE Serological tumor markers are routinely used to monitor tumor onset and progression. In colorectal carcinoma (CRC), the carcinoembryonic antigen (CEA) is roughly elevated in 50% of patients at initial diagnosis. Soluble ICAM-1 (sICAM-1) is elevated in different cancers. The aim of this study was to evaluate the prognostic relevance of sICAM-1 combined with CEA in patients with CRC. METHODS In blood samples of 297 CRC patients, sICAM-1 was determined by ELISA and CEA by microparticle enzyme immunoassay the day before oncologic resection. Separation in patients with sICAM-1high and sICAM-1low was performed by minimum p value approach; separation in CEA normal and elevated was performed according to the established diagnostic cutoff. Clinical data were obtained from the prospective collected data from the Erlangen Registry for Colorectal Carcinomas. RESULTS Cancer-related 5-year survival rate of patients with sICAM-1low (< 290 ng/ml, n = 208) was significantly increased (83.4%) as compared to that of patients with sICAM-1high (≥ 290 ng/ml, n = 89) (66.2%; p < 0.001). Patients with normal CEA concentrations (n = 199; 90.8%) showed a significantly (p < 0.001) improved cancer-related 5-year survival rate compared to patients with elevated CEA concentrations (n = 98; 52.1%). Moreover, high sICAM-1 was an independent risk factor (hazard ratio 1.6) in multivariate analysis. Of note, increased sICAM-1 levels, either within normal or within elevated CEA, allowed to identify high-risk subgroups, both for overall (p < 0.001) and cancer-related survival (p < 0.001). CONCLUSION Application of a novel risk score combining CEA/sICAM-1 serum concentrations allows the identification of high-risk groups for poor survival in CRC patients.
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Affiliation(s)
- Vera S. Schellerer
- Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstr. 12, 91054 Erlangen, Germany
| | - Melanie C. Langheinrich
- Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstr. 12, 91054 Erlangen, Germany
| | - Veronika Zver
- Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstr. 12, 91054 Erlangen, Germany
| | - Robert Grützmann
- Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstr. 12, 91054 Erlangen, Germany
| | - Michael Stürzl
- Division of Molecular and Experimental Surgery, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Olaf Gefeller
- Department of Medical Informatics, Biometry and Epidemiology, Friedrich-Alexander- University of Erlangen-Nürnberg, Erlangen, Germany
| | - Elisabeth Naschberger
- Division of Molecular and Experimental Surgery, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
| | - Susanne Merkel
- Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstr. 12, 91054 Erlangen, Germany
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Multiple mathematical models of diffusion-weighted magnetic resonance imaging combined with prognostic factors for assessing the response to neoadjuvant chemotherapy and radiation therapy in locally advanced rectal cancer. Eur J Radiol 2018; 110:249-255. [PMID: 30599868 DOI: 10.1016/j.ejrad.2018.12.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 10/25/2018] [Accepted: 12/04/2018] [Indexed: 12/16/2022]
Abstract
PURPOSE To investigate whether the apparent diffusion coefficient (ADC), intravoxel incoherent motion (IVIM), and stretched exponential model (SEM) based on histogram analyses derived from the whole-tumor volume combined with prognostic factors can be used to assess the response to chemotherapy and radiation therapy (CRT) in locally advanced rectal cancer (LARC). MATERIALS AND METHODS This study included 60 patients with LARC who underwent diffusion-weighted imaging with 9b values (0-1000s/mm2) before CRT. Histograms derived from the whole-tumor volume were used to obtain the ADC, IVIM (Dslow, Dfast, and f), and SEM parameters (distributed diffusion coefficient (DDC) and α). The histogram metrics and prognostic factors before CRT were compared between pathological complete response (pCR) and non-pCR patients. The receiver operating characteristic (ROC) and the area under the ROC curve (AUC) were generated to analyze the histogram metrics and prognostic factors. RESULTS A significant difference was only found in the tumor volume between the pCR and non-pCR groups (p = 0.033, AUC = 0.740). The ADC mean, DDC median, and most of the histogram metrics were significantly lower in the pCR group than the non-pCR group (p = 0.000-0.025), and AUC was highest for the ADC mean (0.890). Only the Dslow median differed significantly between the two groups (p = 0.023, AUC = 0.721). However, the Dfast, f, and α histogram metrics did not differ significantly between the pCR and non-pCR groups. The AUC for the ADC mean combined with the tumor volume was 0.908, with a sensitivity of 100% and specificity of 81%. The inter-observer agreements were good or excellent for the ADC and SEM histogram parameters but generally fair for IVIM. CONCLUSION The whole-tumor ADC mean combined with the tumor volume was highly accurate for predicting pCR. The IVIM models were inferior to ADC and SEM at predicting pCR.
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Chang SJ, Ge XS, Xu ZY, Qi XW, Chen XP. Lower serum CA125 level, negative vascular invasion, and wild BRAF were strongly associated with better 2-year disease-free survival in patients with stage III colorectal cancer who received adjuvant chemotherapy. Cancer Biomark 2018; 22:161-168. [PMID: 29562502 DOI: 10.3233/cbm-181179] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND Adjuvant chemotherapy plays important role in the comprehensive treatment of patients with stage III colorectal cancer. However, there is few molecular markers for predicting the therapeutic effect. OBJECTIVE To identify factors that could predict adjuvant chemotherapy benefits in patients with stage III colorectal cancer. METHODS The medical records of 294 patients were reviewed and analyzed using the Kaplan-Meier method and Cox analysis. RESULTS Lower CA125 (⩽ 35 u/ml, P= 0.0015) serum levels, stage IIIa (P= 0.0027), 1-3 positive lymph nodes (P= 0.0256), negative vascular invasion (P= 0.0215), lower CA199 (⩽ 27 u/ml, P= 0.0038) serum levels, and wild-type BRAF status (P= 0.0125) were significantly associated with a higher 2-year DFS rate in patients with stage III colorectal cancer. However, in multivariate COX analysis, the association remained significant only for CA125 levels (vs. ⩽ 35 u/ml group, HR 3.341; 95% CI, 1.198-9.316; P= 0.0212), vascular invasion (vs. negative vascular invasion, HR, 2.349; 95% CI, 1.227-4.499; P= 0.01), and BRAF (V600E) (vs. wild Braf, HR, 7.794; 95% CI, 1.867-32.531; P= 0.0049). CONCLUSION Lower CA125 serum levels, negative vascular invasion, and wild-type BRAF status were significantly associated with improved 2-year DFS rates among patient with stage III disease who received adjuvant chemotherapy.
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Affiliation(s)
- Shu-Jian Chang
- Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China
| | - Xiao-Song Ge
- Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China
| | - Zhen-Yu Xu
- Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China
| | - Xiao-Wei Qi
- Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China
| | - Xiao-Ping Chen
- Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214062, Jiangsu, China
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Cancer Antigen 125 (CA125, MUC16) Protein Expression in the Diagnosis and Progression of Pancreatic Ductal Adenocarcinoma. Appl Immunohistochem Mol Morphol 2018; 25:620-623. [PMID: 27093451 DOI: 10.1097/pai.0000000000000368] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive carcinoma, with most patients diagnosed at an advanced stage, with a 5-year survival rate of around 5%. An urgent need exists for identifying better diagnostic, prognostic, and therapeutic markers for this lethal disease. Recently, CA125 has been identified in PDAC, and the aim of this research is to study the changes in CA125 expression during the progression of benign pancreatic tissue (BPT) to PDAC and to assess its value as a biomarker of tumor growth. To address these questions, the cellular levels of CA125 in BPT and PDAC were measured using immunohistochemistry and compared on the basis of tumor staging, and the tissue microarray technology were constructed using resected pancreatic tissues. The staining reactions for each case were evaluated semiquantitatively using the histologic score system. Our investigation demonstrates a consistent and significant upregulation of CA125 during the transition from BPT to PDAC. We also found a direct correlation between CA125 immunohistochemistry score and tumor stage (P=0.02). In conclusion, our data indicate that CA125 plays a direct role in pancreatic carcinogenesis and suggests that it may eventually be used as a diagnostic and/or prognostic biomarker of pancreatic cancer. Prospective studies are recommended to evaluate further the diagnostic and prognostic capabilities of CA125 in PDAC, and further studies are warranted to assess the use of CA125 as a therapeutic marker.
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22
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Boysen AK, Wettergren Y, Sorensen BS, Taflin H, Gustavson B, Spindler KLG. Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer. Tumour Biol 2017; 39:1010428317730976. [DOI: 10.1177/1010428317730976] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.
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Affiliation(s)
| | - Yvonne Wettergren
- Surgical Oncology Laboratory, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Boe Sandahl Sorensen
- Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark
| | - Helena Taflin
- Surgical Oncology Laboratory, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Bengt Gustavson
- Surgical Oncology Laboratory, Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
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Meng Q, Shi S, Liang C, Xiang J, Liang D, Zhang B, Qin Y, Ji S, Xu W, Xu J, Ni Q, Yu X. Diagnostic Accuracy of a CA125-Based Biomarker Panel in Patients with Pancreatic Cancer: A Systematic Review and Meta-Analysis. J Cancer 2017; 8:3615-3622. [PMID: 29151947 PMCID: PMC5687178 DOI: 10.7150/jca.18901] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Accepted: 03/31/2017] [Indexed: 12/14/2022] Open
Abstract
Background: Increasing evidence from recent studies has revealed the association of CA125 with the diagnosis of pancreatic cancer, but inconsistent findings have been reported. We aimed to evaluate the diagnostic value of a serum CA125-based diagnostic panel in predicting malignant pancreatic cancer. Materials and Methods: We searched EMBASE, MEDLINE and Web of Science for relevant articles from inception to October 2016. Methodological quality was evaluated using the Quality Assessment of Comparative Diagnostic Accuracy Studies (QUADAS-2) checklist. The performance characteristics were pooled using random-effects models. The statistical analysis was performed using Meta-Disc 1.4 and Stata Version 12.0 software. Results: A total of 1235 participants pooled from 8 eligible studies were included in the meta-analysis to evaluate the accuracy of tumor predictors for the diagnosis of pancreatic cancer. The pooling accuracy analysis of CA125 alone indicated that the pooled sensitivity was 0.59 (95% CI: 0.54-0.62) and the specificity was 0.78 (95% CI: 0.75-0.82), whereas the serum CA125-based diagnostic panel had a pooled sensitivity of 0.47 (95% CI 0.47-0.51) and a specificity of 0.88 (95% CI 0.86-0.90). Furthermore, the AUC and Q-value of the CA125-based diagnostic panel were 0.89 and 0.82, respectively, which indicated that the CA125-based panel is superior to CA125 or CA19-9 alone in diagnosing pancreatic cancer. No obvious publication bias was found. Conclusions: In summary, a CA125-based diagnostic panel is better at diagnosing pancreatic cancer than a test using CA125 or CA19-9 alone. Further studies should be performed to confirm our conclusion.
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Affiliation(s)
- Qingcai Meng
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Chen Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Jinfeng Xiang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Dingkong Liang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Bo Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Yi Qin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Wenyan Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Jin Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Quanxing Ni
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
- Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
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Tingting H, Di S, Xiaoping C, Xiaohong W, Dong H. High preoperative serum ferritin predicted poor prognosis in non-metastatic colorectal cancer. Saudi Med J 2017; 38:268-275. [PMID: 28251222 PMCID: PMC5387903 DOI: 10.15537/smj.2017.3.16110] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Objectives: To validate the prognostic significance of preoperative serum iron metabolism parameters in non-metastatic colorectal cancer patients treated with curative resection. Methods: We conducted a prospective cohort study in the Department of Surgical Oncology, WuXi 4th People’s Hospital, WuxiChina, between March 2010 and September 2013. The relationships of serum iron metabolism parameters with other variables were examined. The prognostic significance was evaluated using the Kaplan Meier curve and Cox proportional hazards regression model. Results: Five hundred and fourteen patients were eligible for analysis. The levels of the 3 iron metabolism parameters were interdependent. Hemoglobin level was positively correlated with serum iron and transferrin, and was negatively correlated with ferritin. Compared with peri-neural invasion (PNI)-negative patients, PNI-positive patients had higher serum iron (p=0.03) and ferritin levels (p=0.01). Compared with patients with the lowest quartile level of ferritin, patients with the highest quartile level of ferritin had a 2.21 (95% CI: 1.18-4.14) fold increased mortality risk in the univariate and 2.56 (95% CI: 1.10-5.96) in the multivariate Cox proportional hazards models. When stratified by TNM stages, it was only in stage III patients that serum ferritin remained statistically prognostically significant. Conclusions: Preoperative serum ferritin appeared as an independent adverse risk factor in non-metastatic colorectal cancer.
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Affiliation(s)
- Hong Tingting
- Department of Medical Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, People Republic of China. E-mail.
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25
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The role of vitamin D in hepatic metastases from colorectal cancer. Clin Transl Oncol 2017; 20:259-273. [PMID: 28801869 DOI: 10.1007/s12094-017-1735-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 07/30/2017] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) represents a significant health burden worldwide, comprising approximately 10% of annual cancer cases globally. Hepatic metastases are the most common site of CRC metastasis, and are the leading cause of death in CRC patients. There is strong epidemiologic evidence for an inverse association between vitamin D status and risk of CRC; however, the role of vitamin D in the natural history of liver metastases has not yet been investigated. Several researchers have proposed hallmarks of metastases; crucially, metastases can be blocked by interrupting just one rate-limiting step. Vitamin D status has been implicated in each proposed hallmark of metastasis. The aim of this review is to examine the potential role for vitamin D in reducing the development of hepatic metastases from CRC and outline the candidate mechanisms by which vitamin D may mediate these effects. The results of ongoing randomised intervention trials are eagerly awaited to determine whether addressing vitamin D insufficiency in CRC patients could reduce the occurrence of liver metastases, and the consequent morbidity and mortality.
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Tong D, Liu F, Li W, Zhang W. The impacts of surgery of the primary cancer and radiotherapy on the survival of patients with metastatic rectal cancer. Oncotarget 2017; 8:89214-89227. [PMID: 29179513 PMCID: PMC5687683 DOI: 10.18632/oncotarget.19157] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Accepted: 06/28/2017] [Indexed: 12/24/2022] Open
Abstract
The role of surgery of the primary cancer and radiation in metastatic colorectal cancer (mCRC) is still controversial currently, and evidence implied that colon cancer (CC) and rectal cancer (RC) should be treated with difference. Hence we focused on metastatic rectal cancer (mRC) solely to compare the cancer cause-specific survival (CSS) of patients receiving varied treatments of the primary cancer: no treatment, surgery only, radiation only, and surgery plus radiation, based on the records of the Surveillance, Epidemiology, and End Results (SEER) database. A total of 8669 patients were included. Results demonstrated that the 2-year CSS was 28.1% for no treatment group, 30.7% for only radiation group, 50.2% for only surgery group, and 66.5% for surgery plus radiation group, reaching statistical difference (P < 0.001). Furthermore, the CSSs of mRC patients in the surgery group were similar regardless of resection ranges (P = 0.44). Besides, we analyzed the prognostic factors for mRC and found carcinoembryonic antigen (CEA) level, metastasis (M) stage, Tumor (T) stage, tumor size, differentiate grade, age and marital status should be taken into consideration when estimating the prognosis. Particularly, patients with normal CEA level or M1a stage showed a significant survival advantage. Overall, present study suggested that surgery of the primary cancer and radiation might help to improve the survival of mRC patients, especially when both treatments were conducted. Our results may assist clinicians to make better treatment strategy for patients with mRC.
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Affiliation(s)
- Duo Tong
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Fei Liu
- Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Wenhua Li
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
| | - Wen Zhang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
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Wilson MJ, van Haaren M, Harlaar JJ, Park HC, Bonjer HJ, Jeekel J, Zwaginga JJ, Schipperus M. Long-term prognostic value of preoperative anemia in patients with colorectal cancer: A systematic review and meta-analysis. Surg Oncol 2017; 26:96-104. [PMID: 28317592 DOI: 10.1016/j.suronc.2017.01.005] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 01/12/2017] [Accepted: 01/31/2017] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To evaluate the long-term prognostic factor of preoperative anemia in colorectal cancer patients. BACKGROUND Anemia is frequently observed in colorectal cancer patients, with a case incidence of 30 to 67 percent. Besides an indicator of tumor-induced blood loss and inflammation, anemia in cancer is also suggested to be a cause of inferior outcome, possibly via worsening of tumor hypoxia. As surgery is likely to enhance anemia, the long-term prognostic value of preoperative anemia seems most interesting. METHODS Comprehensive searches were carried out in all relevant databases, including MEDLINE, Embase and Web-of-Science. To include studies addressing overall survival, follow-up had to be at least 24 months or till death. For pooling of survival results, a mixed-linear (fixed-effects) model was fit to the reported hazard ratios (HRs) to calculate a pooled estimate and confidence interval. RESULTS We included 12 studies comprising 3588 patients to estimate the association between preoperative anemia and overall survival (OS) and disease-free survival (DFS). In a fixed-effects meta-analysis of eight studies, including both colon and rectal cancer, preoperative anemia was significantly associated with poor OS (HR 1.56; 95% CI 1.30 to 1.88; p < 0.001). A meta-analysis of seven studies also showed that preoperative anemia was significantly associated with poor DFS (HR 1.34; 95% CI 1.11 to 1.61; p = 0.002). Restricted to studies exclusively on colon cancer or rectal cancer, HRs for OS were 1.25 (95% CI 1.00 to 1.55; p = 0.05) and 2.59 (95% CI 1.68 to 4.01; p < 0.001), respectively, while HRs for DFS were 1.21 (95% CI 0.96 to 1.52; p = 0.11) and 1.61 (95% CI 1.18 to 2.21; p = 0.003). CONCLUSION The present meta-analysis reveals that preoperative anemia is significantly associated with decreased long-term OS and DFS in rectal cancer, but not in colon cancer patients, although this meta-analysis is mainly based on retrospective studies with high heterogeneity. These results justify raised awareness about the impact of preoperative anemia on long-term survival.
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Affiliation(s)
- M J Wilson
- TRIP Hemovigilance and Biovigilance Office, Leiden, The Netherlands; Erasmus University Medical Center Rotterdam, Department of Surgery, The Netherlands.
| | - M van Haaren
- OLVG Amsterdam, Department of Internal Medicine, The Netherlands
| | - J J Harlaar
- Westfriesgasthuis Hoorn, Department of Surgery, The Netherlands; VU Medical Center Amsterdam, Department of Surgery, The Netherlands
| | - Hee Chul Park
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Radiation Oncology, Seoul, South Korea
| | - H J Bonjer
- VU Medical Center Amsterdam, Department of Surgery, The Netherlands
| | - J Jeekel
- Erasmus University Medical Center Rotterdam, Department of Neuroscience, The Netherlands
| | - J J Zwaginga
- Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands; Leiden University Medical Center, Department of Immunohematology and Blood Transfusion, The Netherlands
| | - M Schipperus
- Haga Ziekenhuis Den Haag, Department of Hematology, The Netherlands; TRIP Hemovigilance and Biovigilance Office, Leiden, The Netherlands
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Zhang J, Cai Y, Hu H, Lan P, Wang L, Huang M, Kang L, Wu X, Wang H, Ling J, Xiao J, Wang J, Deng Y. Nomogram basing pre-treatment parameters predicting early response for locally advanced rectal cancer with neoadjuvant chemotherapy alone: a subgroup efficacy analysis of FOWARC study. Oncotarget 2016; 7:5053-62. [PMID: 26646794 PMCID: PMC4826265 DOI: 10.18632/oncotarget.6469] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 11/25/2015] [Indexed: 12/12/2022] Open
Abstract
Objective To develop an accurate model with pre-treatment parameters to predict tumor regression and down-staging in locally advanced rectal cancer patients, basing the cohort of preoperative chemotherapy alone in FOWARC study. Patients and Methods From Jan 2011 to Feb 2015, complete data was available for 137 out of 165 patients who received preoperative chemotherapy alone. All pre-treatment clinical parameters were collected. Tumor regression grade (TRG) 0-1 was defined as good regression, and pathological TNM stage (ypTNM) 0-I after neoadjuvant treatment was defined as good down-staging. Nomogram was established to predict tumor regression and down-staging. The predictive performance of the model was assessed with concordance index and calibration plots. Results Of the 137 patients, 10 had TRG 0 (complete regression); 32 patients, TRG 1; and 95 patients, TRG 2 and 3 (poor regression); 56 (40.9%) patients were classified as good down-staging with ypTNM stage 0-I. The predictive nomograms were developed to predict the probability of TRG 0-1 and good down-staging with a C-index of 0.72 (95% CI: 0.604-0.797) and 0.76 (95% CI: 0.681-0.844). Calibration plots showed good statistical performance on internal validation. Predictive factors in the models included tumor length, tumor circumferential extent, age, and ApoA1. Conclusions The model based on available clinical parameters could accurately predict early efficacy with neoadjuvant mFOLFOX6 chemotherapy alone, which might help in patient selection for optimized treatment.
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Affiliation(s)
- Jianwei Zhang
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, Guangdong, P.R. China
| | - Yue Cai
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, Guangdong, P.R. China
| | - Huabin Hu
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, Guangdong, P.R. China
| | - Ping Lan
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun-Yat sen University, Guangzhou, Guangdong, P.R. China
| | - Lei Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun-Yat sen University, Guangzhou, Guangdong, P.R. China
| | - Meijin Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun-Yat sen University, Guangzhou, Guangdong, P.R. China
| | - Liang Kang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun-Yat sen University, Guangzhou, Guangdong, P.R. China
| | - Xiaojian Wu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun-Yat sen University, Guangzhou, Guangdong, P.R. China
| | - Hui Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun-Yat sen University, Guangzhou, Guangdong, P.R. China
| | - Jiayu Ling
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, Guangdong, P.R. China
| | - Jian Xiao
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, Guangdong, P.R. China
| | - Jianping Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun-Yat sen University, Guangzhou, Guangdong, P.R. China
| | - Yanhong Deng
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, Guangdong, P.R. China
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Lee S, Song A, Eo W. Serum Ferritin as a Prognostic Biomarker for Survival in Relapsed or Refractory Metastatic Colorectal Cancer. J Cancer 2016; 7:957-64. [PMID: 27313786 PMCID: PMC4910588 DOI: 10.7150/jca.14797] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2015] [Accepted: 03/16/2016] [Indexed: 12/26/2022] Open
Abstract
Background: This study investigated the prognostic impact of serum ferritin for survival in patients with relapsed or refractory metastatic colorectal cancer (mCRC). Methods: This retrospective cohort study reviewed clinicopathological characteristics and laboratory biomarkers in 120 mCRC patients being treated with Korean Medicine (KM). The overall survival (OS) of patients was calculated using the Kaplan-Meier method, and statistical significance was assessed using the log-rank test. Univariate and multivariate analyses of Cox proportional hazards regression were used to evaluate the prognostic impact for survival in relapsed or refractory mCRC patients. Results: Of the patients, 62.5% had liver metastases, 74.1% underwent greater than second-line chemotherapy, and 80.8% underwent surgery. Median OS was 7.6 months for all patients after the initiation of KM treatment, which was begun 13.7 months, on average, after mCRC diagnosis. Concerning prognostic factors such as the presence of liver metastasis (p = 0.024), high carcinoembryonic antigen level (CEA > 5 ng/mL, p = 0.044), elevated C-reactive protein (CRP ≥ 10.0 mg/L, p = 0.000), high absolute monocyte count (AMC > 413.3 cells/μL, p = 0.034), elevated serum ferritin (ferritin ≥ 150 ng/mL, p = 0.002), low hemoglobin level (Hb < 12 g/dL, p = 0.026) and low albumin (albumin < 3.5 g/dL, p = 0.003) were associated with increased hazard ratios and poor survival. According to the multivariate proportional hazards model with backward and forward manners, albumin (albumin < 3.5 g/dL; hazard ratio (HR) 2.218, 95% confidence interval (CI) 1.135 - 3.990, p = 0.019), CRP (CRP ≥ 10.0 mg/L; HR 2.506, 95% CI 1.644 - 3.822, p = 0.000), CEA (CEA > 5 ng/mL; HR 2.040, 95% CI 1.203 - 3.460, p = 0.008), and serum ferritin (ferritin ≥ 150 ng/mL; HR 1.763, 95% CI 1.169 - 2.660, p = 0.007) were independent prognostic biomarkers of survival in mCRC patients. Conclusions: These results indicate that serum ferritin acts as an independent prognostic biomarker for survival in relapsed or refractory mCRC patients.
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Affiliation(s)
- Sookyung Lee
- 1. Department of Clinical Oncology, College of Korean Medicine, Kyung Hee University
| | - Anna Song
- 2. Department of Clinical Korean Medicine, Graduate School, Kyung Hee University
| | - Wankyu Eo
- 3. Department of Medical Oncology and Hematology, College of Medicine, Kyung Hee University
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Li G, Wang Z, Xu J, Wu H, Cai S, He Y. The prognostic value of lactate dehydrogenase levels in colorectal cancer: a meta-analysis. BMC Cancer 2016; 16:249. [PMID: 27016045 PMCID: PMC4807548 DOI: 10.1186/s12885-016-2276-3] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2015] [Accepted: 03/13/2016] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The prognostic value of lactate dehydrogenase levels in the prognosis of colorectal cancer patients has been assessed for years, although the results remain controversial and heterogeneous. Thus, we comprehensively reviewed the evidence from studies that evaluated lactate dehydrogenase levels in colorectal cancer patients to determine their effect. METHODS The following databases were searched in September 2014 to identify studies that evaluated the prognostic value of lactate dehydrogenase levels in colorectal cancer: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We extracted hazard ratios (HRs) and the associated 95% confidence intervals (CIs) from the identified studies, and performed random-effects model meta-analyses on the overall survival (OS) and progression-free survival (PFS). Thirty-two studies with a cumulative sample size of 8,261 patients were included in our analysis. RESULTS Our meta-analyses revealed that high levels of lactate dehydrogenase were associated with poor OS (HR, 1.75; 95% CI, 1.52-2.02) in colorectal cancer patients. However, this effect was not obvious in the OS of non-metastatic colorectal cancer patients (HR, 1.21; 95% CI, 0.79-1.86). The prognostic value of lactate dehydrogenase levels on PFS was also not confirmed (HR, 1.36; 95% CI, 0.98-1.87). Subgroup analyses revealed that the prognostic significance of lactate dehydrogenase was independent of study location, patient age, number of patients, metastasis, chemotherapy with anti-angiogenesis drugs, study type, or risk of bias. CONCLUSIONS Our results indicate that high lactate dehydrogenase levels are associated with poor OS among colorectal cancer patients, although these levels are not significant predictors of PFS.
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Affiliation(s)
- Guanghua Li
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong Province People’s Republic of China
| | - Zhao Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong Province People’s Republic of China
| | - Jianbo Xu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong Province People’s Republic of China
| | - Hui Wu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong Province People’s Republic of China
| | - Shirong Cai
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong Province People’s Republic of China
| | - Yulong He
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong Province People’s Republic of China
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Lech G, Słotwiński R, Słodkowski M, Krasnodębski IW. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances. World J Gastroenterol 2016; 22:1745-1755. [PMID: 26855534 PMCID: PMC4724606 DOI: 10.3748/wjg.v22.i5.1745] [Citation(s) in RCA: 276] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2015] [Revised: 10/05/2015] [Accepted: 12/21/2015] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.
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Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients. Gastroenterol Res Pract 2015; 2016:9701574. [PMID: 26858756 PMCID: PMC4706938 DOI: 10.1155/2016/9701574] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Accepted: 07/15/2015] [Indexed: 12/31/2022] Open
Abstract
Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6) in colorectal cancer (CRC). Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS) and disease-free survival (DFS) rates according to IL-6 status were calculated for all patients and according to disease stage. Results. The mean IL-6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP) and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients. Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence.
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Zhang LN, OuYang PY, Xiao WW, Yu X, You KY, Zeng ZF, Xu RH, Gao YH. Elevated CA19-9 as the Most Significant Prognostic Factor in Locally Advanced Rectal Cancer Following Neoadjuvant Chemoradiotherapy. Medicine (Baltimore) 2015; 94:e1793. [PMID: 26559251 PMCID: PMC4912245 DOI: 10.1097/md.0000000000001793] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
It remains controversial regarding the prognostic significance of carbohydrate antigen 19-9 (CA19-9) for locally advanced rectal cancer (LARC) (T3-4/N+) patients with neoadjuvant chemoradiotherapy (neo-CRT). And it is unknown whether CA19-9 can identify patients who may benefit from adjuvant chemotherapy.Overall, 303 LARC patients with neo-CRT between 2004 and 2010 were recruited. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival across pretreatment CA19-9 were estimated by Kaplan-Meier method and Cox regression model.In univariate analysis, elevated CA19-9 (>35 U/mL) was significantly correlated with poor OS (P = 0.003), DFS (P = 0.001), and DMFS (P = 0.039). Adjusting for the known covariates, CA19-9 was significantly associated with OS (HR = 1.86, 95% CI 1.03-3.34, P = 0.039) and DFS (HR = 1.74, 95% CI 1.08-2.80, P = 0.024). In the elevated CA19-9 subgroup, patients with adjuvant chemotherapy got much better OS (P < 0.001) and DFS (P = 0.016) than those without. In consideration of both CA19-9 and carcinoembryonic antigen (CEA), we found that patients with both elevated CA19-9 and CEA (>5 ng/mL) got the worst OS (P = 0.021) and DFS (P = 0.006), and significantly benefited from adjuvant chemotherapy in OS (P < 0.001) and DFS (P = 0.026).Pretreatment CA19-9 level is a significant prognostic indicator in patients with LARC following neo-CRT. The addition of CA19-9 to CEA is valuable to discriminate the appropriate patients for adjuvant chemotherapy.
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Affiliation(s)
- Lu-Ning Zhang
- From the Department of Radiation Oncology (L-NZ, P-YOY, W-WX, XY, Z-FZ, Y-HG), Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong (R-HX) and Department of Oncology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (K-YY)
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Ni XC, Yi Y, Fu YP, He HW, Cai XY, Wang JX, Zhou J, Fan J, Qiu SJ. Serum amyloid A is a novel prognostic biomarker in hepatocellular carcinoma. Asian Pac J Cancer Prev 2015; 15:10713-8. [PMID: 25605163 DOI: 10.7314/apjcp.2014.15.24.10713] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To investigate the prognostic value of serum amyloid A (SAA) in patients with hepatocellular carcinoma (HCC) undergoing surgery. MATERIALS AND METHODS Preoperative serum samples of 328 patients with HCC who underwent curative resection and of 47 patients with benign liver lesion were assayed. Serum levels of SAA were measured by enzyme-linked immunosorbent assay and its correlations with clinicopathological characteristics and survival were explored. RESULTS Levels of SAA were significantly higher in patients with HCC than those with benign liver lesion. There were strong correlations between preoperative serum SAA level and tumor size and more advanced BCLC stage. On univariate analysis, elevated SAA was associated with reduced disease-free survival and overall survival (p=0.001 and 0.03, respectively). Multivariate analyses showed that serum SAA level was an independent prognostic factor for overall survival (hazard ratio 2.80, p=0.01). CONCLUSIONS High SAA serum level is a novel biomarker for the prognosis of HCC patients.
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Affiliation(s)
- Xiao-Chun Ni
- Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, China E-mail :
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Borda A, Prieto C, Jiménez J, Vila J, Zozaya JM, Borda F. [Prognostic value of preoperative carcinoembryogenic antigen: Is it useful in all stages of colorectal cancer?]. GASTROENTEROLOGIA Y HEPATOLOGIA 2015; 39:191-8. [PMID: 26117267 DOI: 10.1016/j.gastrohep.2015.05.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Revised: 05/05/2015] [Accepted: 05/06/2015] [Indexed: 01/07/2023]
Abstract
INTRODUCTION Recent reports have reopened discussion of the prognostic value of elevated pre-treatment carcinoembryonic antigen (CEA) levels in colorectal cancer. Due to the discrepancies in the published results, we aimed to analyze the possible predictive value of CEA, both overall and in different tumoral stages in our environment. PATIENTS AND METHODS We retrospectively studied 303 consecutive patients with colorectal cancer resected with curative intent by analysing tumor-related mortality. The frequency of patients with increased CEA levels (> 5mg/l) was registered. Univariate and multivariate analyses of survival curves were performed, comparing patients with increased CEA levels and those with CEA levels within normal limits, both in the overall series and in the different pTNM tumoral stages. RESULTS Frequency of patients with CEA>5mg/l was 31%. The median clinical follow-up was 83 months. A poor survival rate was registered in the multivariate analysis of the whole series in patients with high CEA levels: hazard ratio (HR)=1.81; 95% confidence interval (95% CI)=(1.15-3.10); P=.012. This predictive value was only maintained in stage II in the survival analysis of the distinct tumoral stages (n=104): HR=3.02; 95% CI=(1.22-7.45); P=.017. CONCLUSIONS Before treatment, 31% of our patients with colorectal cancer resected with curative intent had pathological CEA values. In the overall series, a high pretreatment CEA level showed an independent prognostic value for poor survival. When pTNM tumoral stages were analyzed separately, CEA level had predictive value only in pTNM II tumors.
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Affiliation(s)
- Ana Borda
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España.
| | - Carlos Prieto
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
| | - Javier Jiménez
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
| | - Juan Vila
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
| | - José Manuel Zozaya
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
| | - Fernando Borda
- Servicio de Digestivo, Complejo Hospitalario de Navarra, Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Pamplona, España
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Giessen-Jung C, Nagel D, Glas M, Spelsberg F, Lau-Werner U, Modest DP, Schulz C, Heinemann V, Di Gioia D, Stieber P. Preoperative serum markers for individual patient prognosis in stage I-III colon cancer. Tumour Biol 2015; 36:7897-906. [PMID: 25953265 DOI: 10.1007/s13277-015-3522-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Accepted: 04/28/2015] [Indexed: 12/20/2022] Open
Abstract
Carcinoembryonic antigen (CEA) remains the only recommended biomarker for follow-up care of colorectal cancer (CRC), but besides CEA, several other serological parameters have been proposed as prognostic markers for CRC. The present retrospective analysis investigates a comprehensive set of serum markers with regard to cancer-specific survival (CSS) and disease-free survival (DFS). A total of 472 patients with colon cancer underwent surgery for curative intent between January 1988 and June 2007. Preoperative serum was analyzed for the following parameters: albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin (βhCG), bilirubin, cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), CA 72-4, CEA, C-reactive protein (CRP), cytokeratin-19 soluble fragment (CYFRA 21-1), ferritin, gamma-glutamyltransferase (γGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate dehydrogenase (LDH), serum amyloid A (SAA), and 25-hydroxyvitamin D. After a median follow-up period of 5.9 years, the overall 3- and 5-year CSS was 91.7 and 84.9 % and DFS rates were 82.7 % (3 years) and 77.6 % (5 years). Multivariate analyses confirmed preoperative CEA as an independent prognostic factor with regard to CSS and DFS. CA 19-9 and γGT also provided prognostic value for CSS and DFS, respectively. Younger age was negatively associated with DFS. According to UICC stage, CEA provided significant prognostic value with regard to CSS and DFS, while CA 19-9 was only prognostic for CSS. Combined analysis is able to identify patients with favorable prognosis. In addition to tumor baseline parameters, preoperative CEA could be confirmed as prognostic marker in colon cancer. CA 19-9 and γGT also provide additional prognostic value with regard to survival and recurrence in stage III and stage I disease, respectively. The combined use of CEA together with CA 19-9 and γGT improve risk-adapted post-op surveillance.
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Affiliation(s)
- Clemens Giessen-Jung
- Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany.
| | - Dorothea Nagel
- Institute of Laboratory Medicine, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Maria Glas
- Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Fritz Spelsberg
- Department of Surgery, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Ulla Lau-Werner
- Department of Surgery, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Dominik Paul Modest
- Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Christoph Schulz
- Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Volker Heinemann
- Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Dorit Di Gioia
- Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
| | - Petra Stieber
- Institute of Laboratory Medicine, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377, Munich, Germany
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