Background: Microsatellite instability (MSI) is a distinct molecular phenotype of colorectal cancer related to prognosis and tumour response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the differential impact of MSI between colon and rectal cancers as a marker of prognosis and chemotherapeutic response.
Methods: PCR-based MSI assay was performed on 1125 patients. Six hundred and sixty patients (58.7%) had colon cancer and 465 patients (41.3%) had rectal cancer.
Results: Among 1125 patients, 106 (9.4%) had high-frequency MSI (MSI-H) tumours. MSI-H colon cancers (13%) had distinct phenotypes including young age at diagnosis, family history of colorectal cancer, early Tumor, Node, Metastasis (TNM) stage, proximal location, poor differentiation, and high level of baseline carcinoembryonic antigen (CEA), while MSI-H rectal cancers (4.3%) showed similar clinicopathological characteristics to MSS/MSI-L tumours except for family history of colorectal cancer. MSI-H tumours were strongly correlated with longer disease free survival (DFS) (P=0.005) and overall survival (OS) (P=0.009) than MSS/MSI-L tumours in colon cancer, while these positive correlations were not observed in rectal cancers. The patients with MSS/MSI-L tumours receiving 5-FU-based chemotherapy showed good prognosis (P=0.013), but this positive association was not observed in MSI-H (P=0.104).
Conclusion: These results support the use of MSI status as a marker of prognosis and response to 5-FU-based chemotherapy in patients with colon cancers. Further study is mandatory to evaluate the precise role of MSI in patients with rectal cancers and the effect of 5-FU-based chemotherapy in MSI-H tumours.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejca.2011.10.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Rapid biomonitoring of fluoropyrimidine-based chemotherapy drugs and their biometabolites in colorectal cancer patients' blood samples using an in-syringe-based fast drug extraction technique followed by LC-MS/MS analysis.
J Chromatogr A
January 2025
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University (KMU), Kaohsiung City-807, Taiwan; Research Center for Precision Environmental Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung City-807, Taiwan; PhD Program in Environmental and Occupational Medicine, College of Medicine, Kaohsiung Medical University (KMU), Kaohsiung City-807, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital (KMUH), Kaohsiung Medical University, Kaohsiung, City-807, Taiwan; Department of Chemistry, National Sun Yat-sen University (NSYSU), Kaohsiung City, 804, Taiwan. Electronic address:
Patients with dihydropyrimidine dehydrogenase (DPD) deficiency in peripheral mononuclear cells are at higher risk of severe toxicity due to the improper dose of fluorouracil-based chemotherapy drugs, which has become an essential aspect for consideration in clinical studies. 5-fluorouracil (5-FU) is a first-line and second-line chemotherapy drug in adjuvant, neoadjuvant, or palliative therapy settings to treat solid tumors and cancers. In this work, a novel in-syringe-based fast drug extraction (IS-FaDEx) technique followed by UHPLC-MS/MS detection was developed for rapid biomonitoring of 5-FU and its biometabolites in human blood samples.
View Article and Find Full Text PDFTargeting the mevalonate pathway enhances the efficacy of 5-fluorouracil by regulating pyroptosis.
Med Oncol
November 2024
Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
The 5-fluorouracil (5-FU)-based chemotherapy regimen is a primary strategy for treating pancreatic cancer (PC). However, challenges related to 5-FU resistance persist. Investigating the mechanisms of 5-FU resistance and identifying a clinically viable therapeutic strategy are crucial for improving the prognosis of PC.
View Article and Find Full Text PDFOvercoming Therapy Resistance in Colorectal Cancer: Targeting the Rac1 Signaling Pathway as a Potential Therapeutic Approach.
Cells
October 2024
Instituto de Inmunología Clínica y Experimental de Rosario (IDICER, CONICET-UNR), Facultad de Ciencias Médicas (UNR), Rosario 2000, Argentina.
Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide and is responsible for numerous deaths. 5-fluorouracil (5-FU) is an effective chemotherapy drug commonly used in the treatment of CRC, either as monotherapy or in combination with other drugs. However, half of CRC cases are resistant to 5-FU-based therapies.
View Article and Find Full Text PDFSurgical treatment of urachal adenocarcinoma with lung metastasis: A case report and literature review.
Thorac Cancer
December 2024
Department of Thoracic Surgery, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.
Article Synopsis
- * Most urachal cancers are classified as intestinal adenocarcinomas (90%), and they often occur in the lower urachal tube or bladder dome, leading to late diagnoses due to the silent nature of early stages.
- * Treatment options for this aggressive cancer include surgery and chemotherapy (like cisplatin), with some patients showing positive responses to targeted therapies; a case study highlighted successful surgical treatment for a patient with advanced disease.
An RNA damage response network mediates the lethality of 5-FU in colorectal cancer.
Cell Rep Med
October 2024
Center for Precision Cancer Medicine, David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Surgery, Beth Israel Medical Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address:
Article Synopsis
- 5-fluorouracil (5-FU) is an important cancer treatment that mostly works by blocking a specific enzyme, leading to DNA damage, but clinical trials show it doesn't work well with certain other drugs for colorectal cancer.
- Research indicates that 5-FU actually kills colorectal cancer cells by targeting RNA during the process of making ribosomes, rather than mainly causing DNA damage, which some cancer types are more sensitive to.
- Strategies that increase ribosome production may enhance the effectiveness of 5-FU, suggesting that combining treatments that focus on this aspect could improve outcomes in cancer therapy.
Want 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!