Comprehensive functional genomic analyses link APC somatic mutation and mRNA-miRNA networks to the clinical outcome of stage-III colorectal cancer patients

Sum Fu Chiang, Heng Hsuan Huang, Wen Sy Tsai, Bertrand Chin-Ming Tan, Chia Yu Yang, Po Jung Huang, Ian Yi-Feng Chang, Jiarong Lin, Pei Shan Lu, En Chin, Yu Hao Liu, Jau Song Yu, Jy Ming Chiang, Hsin Yuan Hung, Jeng Fu You, Hsuan Liu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations


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 from 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.

Original languageEnglish
Pages (from-to)347-360
Number of pages14
JournalBiomedical Journal
Issue number2
StatePublished - 04 2022

Bibliographical note

Publisher Copyright:
© 2021 Chang Gung University


  • Adenomatous polyposis coli
  • Colorectal cancer
  • Exome
  • Next-generation sequencing
  • Transcriptome


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