Wang Yu-Han, Chang Shih-Ching, Ansar Muhamad, Hung Chin-Sheng, Lin Ruo-Kai
School of Medicine, Tzu Chi University, Hualien City 97071, Taiwan.
Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
Biomedicines. 2021 Apr 22;9(5):453. doi: 10.3390/biomedicines9050453.
Colorectal cancer (CRC) arises from chromosomal instability, resulting from aberrant hypermethylation in tumor suppressor genes. This study identified hypermethylated genes in CRC and investigated how they affect clinical outcomes. Methylation levels of specific genes were analyzed from The Cancer Genome Atlas dataset and 20 breast cancer, 16 esophageal cancer, 33 lung cancer, 15 uterine cancer, 504 CRC, and 9 colon polyp tissues and 102 CRC plasma samples from a Taiwanese cohort. In the Asian cohort, () had twofold higher methylation in 44.4% of patients with colonic polyps, 37.3% of plasma from CRC patients, and 72.6% of CRC tissues, which was connected to vascular invasion and high microsatellite instability. Furthermore, hypermethylation was detected in other gastrointestinal cancers. In the Asian CRC cohort, low mRNA expression was found in 45.1% of patients and was connected to lymph node metastasis. Multivariate Cox proportional-hazards survival analysis revealed that hypermethylation in women and low mRNA expression were associated with overall survival. In the Western CRC cohort, hypermethylation was also connected to overall survival and lower chemotherapy and antimetabolite response rates. In conclusion, hypermethylation contributes to the development of CRC in both Asian and Western populations.
结直肠癌(CRC)源于染色体不稳定,这是由肿瘤抑制基因的异常高甲基化引起的。本研究确定了CRC中高甲基化的基因,并研究了它们如何影响临床结果。从癌症基因组图谱数据集以及来自台湾队列的20例乳腺癌、16例食管癌、33例肺癌、15例子宫癌、504例CRC、9例结肠息肉组织和102例CRC血浆样本中分析了特定基因的甲基化水平。在亚洲队列中,()在44.4%的结肠息肉患者、37.3%的CRC患者血浆和72.6%的CRC组织中甲基化水平高出两倍,这与血管侵犯和高微卫星不稳定性有关。此外,在其他胃肠道癌症中也检测到()高甲基化。在亚洲CRC队列中,45.1%的患者中发现()mRNA表达较低,且与淋巴结转移有关。多变量Cox比例风险生存分析显示,女性中的高甲基化和低mRNA表达与总生存期相关。在西方CRC队列中,()高甲基化也与总生存期以及较低的化疗和抗代谢物反应率有关。总之,()高甲基化在亚洲和西方人群中均促进了CRC的发生。