Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Biomed J. 2022 Apr;45(2):347-360. doi: 10.1016/j.bj.2021.03.001. Epub 2021 Mar 16.
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.
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.
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.
For stage III CRC, patients with mutated APC had better overall and recurrence free survival.
结直肠癌（CRC）是全球范围内的一个主要健康问题，但在结局方面表现出区域性和/或环境差异，尤其是对于 III 期 CRC 患者。
从 2014 年到 2016 年，对来自台湾长庚纪念医院的 60 名 I-IV 期 CRC 患者的肿瘤和相邻正常组织样本进行了配对分析，使用下一代测序。对配对肿瘤组织的 DNA、mRNA 和 miRNA 序列进行了分析。进行了一项包含生存分析的观察性研究。还整合并比较了癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）的在线数据集。
突变率最高的基因是腺瘤性息肉病基因（APC）（75.0%），其次是 TP53（70.0%）、KRAS（56.6%）和 TTN（48.3%）。APC 也是 TCGA 和 ICGC 数据集中突变最频繁的基因。令人惊讶的是，对于非转移性病例（I-III 期），APC 突变的 CRC 患者在总生存（p=0.041）和无复发生存（p=0.0048）方面有更好的结果。特别是对于 III 期 CRC，总生存率分别为 94.4%和 67.7%（p=0.018），无复发生存率分别为 94.4%和 16.7%（p=0.00044）。进一步的临床和基因表达分析表明，APC wt 标本在更大程度上表现出较差的分化状态以及 EGFR 上调，为这些患者的不良预后提供了分子基础。最后，基于整合的转录组分析，我们构建了 III 期 CRC 疾病复发的 mRNA-miRNA 网络，并发现了这种临床情况的潜在治疗靶点。
对于 III 期 CRC，APC 突变的患者具有更好的总生存和无复发生存。
