Background/aim: Rectal cancer accounts for approximately one-third of all colorectal cancers. Currently, the standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) with capecitabine or 5-fluorouracil followed by curative surgery. Unfortunately, only 20% of patients with LARC present complete pathological response after CRT, whereas in 20-40% cases the response is poor or absent. The aim of our study was to evaluate whether microRNAs (miRNAs) in tumor biopsy specimen have the potential to predict therapeutic response in LARC patients.
Patients And Methods: In total 87 LARC patients treated by CRT were enrolled in our prospective study. To identify predictive miRNAs, we used small RNA sequencing in 40 tumor biopsy samples of LARC patients (20 responders, 20 non-responders) and qPCR validation of selected miRNA candidates.
Results: In the discovery phase of the study, we identified 69 miRNAs to have significantly different expression between the group of responders (TRG 1,2) and a group of non-responders (TRG 4,5) to neoadjuvant CRT. Among these miRNAs, 48 showed a lower expression and 21 showed higher expression in tumor tissues from poorly responding LARC patients. Five miRNAs were selected for validation, but only miR-487a-3p was confirmed to have a significantly higher expression in the tumor biopsy specimens of non-responders to neoadjuvant CRT (p<0.0006, AUC=0.766). Gene Ontology (GO) clustering and pathway enrichment analysis of the miR-487a-3p mRNA targets, revealed potential mechanisms behind miR-487a-3p roles in chemoradioresistance (e.g. TGF-beta signaling pathway, protein kinase activity, double-stranded DNA binding, or microRNAs in cancer).
Conclusion: By combination of miRNA expression profiling and integrative computational biology we identified miR-487a-3p as a potential predictive biomarker of CRT response in LARC patients.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259892 | PMC |
| http://dx.doi.org/10.21873/cgp.20185 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Risk Factors for Anastomotic Leakage: A Comprehensive Single-Center Analysis of Colorectal Anastomoses for Ovarian and Gastrointestinal Cancers.
Ann Surg Oncol
January 2025
Department Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.
Background: Anastomotic leakage (AL) is a major complication in colorectal surgery, particularly following rectal cancer surgery, necessitating effective prevention strategies. The increasing frequency of colorectal resections and anastomoses during cytoreductive surgery (CRS) for peritoneal carcinomatosis further complicates this issue owing to the diverse patient populations with varied tumor distributions and surgical complexities. This study aims to assess and compare AL incidence and associated risk factors across conventional colorectal cancer surgery (CRC), gastrointestinal CRS (GI-CRS), and ovarian CRS (OC-CRS), with a secondary focus on evaluating the role of protective ostomies.
View Article and Find Full Text PDFASO Visual Abstract: Patterns of Care and Oncologic Outcomes After Pelvic Exenteration for Locally Advanced Rectal Cancer in the United States.
Ann Surg Oncol
January 2025
Division of Colon and Rectal Surgery, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
A word of caution in the functional monitoring of patients after rectal cancer surgery: a multicentre observational study.
Tech Coloproctol
January 2025
Colorectal Surgery Unit, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona UAB, Barcelona, Spain.
Background: Patients with rectal cancer often experience adverse effects on urinary, sexual, and digestive functions. Despite recognised impacts and available treatments, they are not fully integrated into follow-up protocols, thereby hindering appropriate interventions. The aim of the study was to discern the activities conducted in our routine clinical practice outside of clinical trials.
View Article and Find Full Text PDFLongitudinal circulating tumor DNA monitoring in predicting response to short-course radiotherapy followed by neoadjuvant chemotherapy and camrelizumab in locally advanced rectal cancer: data from a Phase Ⅲ clinical trial (UNION).
Cancer Lett
January 2025
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Key Laboratory of Precision Radiation Oncology, Wuhan 430022, China. Electronic address:
This study, conducted as part of a multicenter phase III clinical trial, aimed to assess the utility of circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) in comparing the efficacy of short-course and long-course chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). A total of 244 plasma samples from 79 LARC patients undergoing neoadjuvant therapy (NAT) before surgery were collected at various time points. Targeted deep sequencing using a novel MRD panel was performed.
View Article and Find Full Text PDFResveratrol and capsaicin as safer radiosensitizers for colorectal cancer compared to 5-fluorouracil.
Biomed Pharmacother
January 2025
University of Bordeaux, Bordeaux, France; INSERM U1312, Bordeaux Institute of Oncology - BRIC, BioGo Team, Bordeaux, France; Biochemistry Department, Bordeaux University Hospital (CHU de Bordeaux), Bordeaux, France. Electronic address:
Background And Aim: Standard rectal cancer treatment includes neoadjuvant radiotherapy sensitized by 5-fluorouracil (5-FU) chemotherapy. However, 5-FU increased chemoradiotherapy response rate comes with significant toxicity, especially in older, frail patients. The development of alternatives to chemotherapy enabling radiosensitization with limited systemic toxicity is therefore needed to improve patient management.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!