Mutated DNA Damage Repair Pathways Are Prognostic and Chemosensitivity Markers for Resected Colorectal Cancer Liver Metastases
| Autor: | Quan Bao, Da Xu, Wei Liu, Juan Li, Ge Jin, Baocai Xing, Li-Jun Wang, Xiaoyu Zhang, Hongwei Wang, Kemin Jin, Chun-He Yang, Yan-Yan Wang, Ming Liu, Kun Wang, Xiao-Luan Yan, Li-Juan Liu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Colorectal cancer medicine.medical_treatment colorectal cancer liver metastasis medicine.disease_cause lcsh:RC254-282 Metastasis 03 medical and health sciences 0302 clinical medicine medicine DNA damage repair Original Research Mutation Chemotherapy business.industry Hazard ratio medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Oxaliplatin body regions 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research next-generation sequencing prognosis Signal transduction chemo-sensitivity Carcinogenesis business medicine.drug |
| Zdroj: | Frontiers in Oncology, Vol 11 (2021) Frontiers in Oncology |
| Popis: | Deficiency of the DNA damage repair (DDR) signaling pathways is potentially responsible for genetic instability and oncogenesis in tumors, including colorectal cancer. However, the correlations of mutated DDR signaling pathways to the prognosis of colorectal cancer liver metastasis (CRLM) after resection and other clinical applications have not been fully investigated. Here, to test the potential correlation of mutated DDR pathways with survival and pre-operative chemotherapy responses, tumor tissues from 146 patients with CRLM were collected for next-generation sequencing with a 620-gene panel, including 68 genes in 7 DDR pathways, and clinical data were collected accordingly. The analyses revealed that 137 of 146 (93.8%) patients had at least one mutation in the DDR pathways. Mutations in BER, FA, HRR and MMR pathways were significantly correlated with worse overall survival than the wild-types (P < 0.05), and co-mutated DDR pathways showed even more significant correlations (P < 0.01). The number of mutated DDR pathways was also proved an independent stratifying factor of overall survival by Cox multivariable analysis with other clinical factors and biomarkers (hazard ratio = 9.14; 95% confidence interval, 1.21–68.9; P = 0.032). Additionally, mutated FA and MMR pathways were positively and negatively correlated with the response of oxaliplatin-based pre-operative chemotherapy (P = 0.0095 and 0.048, respectively). Mutated DDR signaling pathways can predict pre-operative chemotherapy response and post-operative survival in CRLM patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|