右左半结肠癌分子生物学差异研究进展

Role of consensus molecule subtypes and other biological characteristics in the right and left-sided colon cancer

目的右半结肠癌(right-sided colon cancer,RCC)和左半结肠癌(left-sided colon cancer,LCC)分子亚型等生物学特性的不同受到了越来越多的关注,它们可能是两种不同的疾病。本研究分析右左半结肠癌关键分子差异,揭示两者临床结果之间的异质性。方法应用中国知网、PubMed、Web of Science中英文数据库,以"右半结肠癌、左半结肠癌和生物学特性"为关键词,检索2011-01-2017-12相关文献。纳入标准:(1)正常右左半结肠差异;(2)右左半结肠癌关键分子差异;(3)右左半结肠癌临床结果异质性。排除标准:(1)综述类文献;(2)研究资料缺失或质量较差。根据纳入标准与排除标准,符合分析的文献32篇。结果右左半结肠不同的胚胎学起源、致癌毒素和微生物群暴露等潜在的导致了RCC和LCC生物学特性及生存预后的差异。RCC更容易通过CpG岛甲基化(CpG island methylator pheno-type,CIMP)获得全基因组甲基化,通过微卫星不稳定(microsatellite instability,MSI)获得超突变及B型快速加速纤维肉瘤(B-rapidly accelerated fibrosarcoma,BRAF)突变。LCC更常见的是染色体不稳定(chromosomal instability,CIN)、人类表皮生长因子受体(epidermal growth factor receptor,EGFR)或人类表皮生长因子受体-2(human epidermal growth factor receptor-2,HER2)的扩增,常过表达表皮调节蛋白。同时,4个分子亚型(consensus molecular subtypes,CMSs)即CMS1、CMS2、CMS3和CMS4,在两者的分布也不同,CMS1和CMS3多见于RCC,CMSs分析进一步阐明RCC和LCC不同的生物学特性。在预后上,Ⅳ期RCC较LCC预后显著较差,而Ⅰ~Ⅲ期左右半结肠癌的预后差异尚存争议。结论RCC和LCC上CMSs等生物学差异,为个体化治疗提供了重要的依据。

OBJECTIVE The biologic distinction including consensus molecular subtypes（CMSs） between right-sided colon cancer（RCC） and left-sided colon cancer（LCC） has attracted more and more attention, because they may be two different diseases. This review described the key molecular and genomic differences between RCC and LCC, shedding light on the heterogeneity of clinical outcomes between them. METHODS The relevant literatures published between January 20ll and December 2017 in CNKI, PubMed, Web of Science were collected, using the terms ＂right-sided colon cancer＂,＂left-sided colon cancer＂ and ＂biological characteristic＂. Inclusion criteria： （1） differences between normal right and left-sided colon~ （2）the key molecules and genomes differences between RCC and LCC; （3） the heterogeneity of clini- cal outcomes between RCC and LCC. Exclusion criteria： （1）review~ （2）lack of research data or poor quality of literature. Finally, a total of 32 articles were included. RESULTS The distinct embryologic origins, differential exposures to carci- nogenic toxins and microbiota in the right and left-sided colon may cause different biological characteristics and prognosis of RCC and LCC. RCC is more likely to be genome-wide hypermethylation via the CpG island methylator phenotype（CI- MP）, hypermutated state via microsatellite instability, and B-rapidly accelerated fibrosarcoma（BRAF） mutation. LCC is more often chromosome instable and human epidermal growth factor receptor（EGFR or HER2） amplification, and more frequently epiregulin overexpression. Meanwhile, the 4 consensus molecular subtypes（CMSs） are also different in RCC and LCC, and CMS1 and CMS3 are more common in RCC. The analysis of CMSs further clarified the different biologic subtypes of colon cancer. RCC have a worse prognosis than LCC in stage IV, although it is still disputed in stage Ⅰ-Ⅲ.CONCLUSION The important biological differences between RCC and LCC may provide opportunities for personalize therapy.