Comprehensive functional genomic analyses link APC somatic mutation and mRNA-miRNA networks to the clinical outcome of stage-III colorectal cancer patients
| Autor: | En Chin, Jy-Ming Chiang, Sum-Fu Chiang, Jau-Song Yu, Wen-Sy Tsai, Jeng-Fu You, Yu-Hao Liu, Jiarong Lin, Hsin-Yuan Hung, Po-Jung Huang, Heng Hsuan Huang, Chia-Yu Yang, Ian Yi-Feng Chang, Pei-Shan Lu, Bertrand Chin-Ming Tan, Hsuan Liu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Genes APC Colorectal cancer Adenomatous polyposis coli Adenomatous Polyposis Coli Protein medicine.disease_cause Transcriptome 03 medical and health sciences 0302 clinical medicine Germline mutation Internal medicine microRNA Medicine Humans RNA Messenger Stage (cooking) Survival analysis biology business.industry General Medicine Genomics medicine.disease MicroRNAs 030104 developmental biology Adenomatous Polyposis Coli 030220 oncology & carcinogenesis Mutation biology.protein KRAS Neoplasm Recurrence Local business Colorectal Neoplasms |
| Zdroj: | Biomedical journal. 45(2) |
| ISSN: | 2320-2890 |
| Popis: | Background Colorectal cancer (CRC) is a major health concern globally, but exhibits regional and/or environmental distinctions in terms of outcome especially for patients with stage III CRC. Methods From 2014 to 2016, matched pairs of tumor and adjacent normal tissue samples from 60 patients with stage I–IV CRC Chang Gung Memorial Hospital in Taiwan were analyzed using next-generation sequencing. The DNA, mRNA, and miRNA sequences of paired tumor tissues were profiled. An observational study with survival analysis was done. Online datasets of The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) were also integrated and compared. Results The gene that exhibited the highest mutation rate was adenomatous polyposis coli (APC) (75.0%), followed by TP53 (70.0%), KRAS (56.6%), and TTN (48.3%). APC was also the most frequently mutated gene in TCGA and ICGC datasets. Surprisingly, for non-metastatic cases (stages I-III), CRC patients with mutated APC had better outcome in terms of overall survival (p = 0.041) and recurrence free survival (p = 0.0048). Particularly for stage III CRC, the overall survival rate was 94.4% and 67.7%, respectively (p = 0.018), and the recurrence free survival rate was 94.4% and 16.7%, respectively (p = 0.00044). Further clinical and gene expression analyses revealed that the APC wt specimens to a greater extent exhibit poor differentiation state as well as EGFR upregulation, providing molecular basis for the poor prognosis of these patients. Finally, based on integrated transcriptome analysis, we constructed the mRNA-miRNA networks underlying disease recurrence of the stage III CRC and uncovered potential therapeutic targets for this clinical condition. Conclusion For stage III CRC, patients with mutated APC had better overall and recurrence free survival. |
| Databáze: | OpenAIRE |
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