Molecular markers and pathway analysis of colorectal carcinoma in the Middle East
Molecular markers and pathway analysis of colorectal carcinoma in the Middle East
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DOI：
10.1002/cncr.29580
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发表时间：
2015-11-01
期刊：
影响因子：
6.2
通讯作者：
Al-Kuraya, Khawla S.
中科院分区：
文献类型：
--
作者：
Beg, Shaham;Siraj, Abdul K.;Al-Kuraya, Khawla S.
结直肠癌（CRC）是世界上最常见的癌症之一。近年来，由遗传和表观遗传因素引起的传统、交替和锯齿状通路的整合通路被认为在结直肠癌的发病机制中起作用;然而，据作者所知，在不同种族中关于这些分子途径的信息很少。方法对770例CRC标本进行微卫星不稳定性，BRAF，500例患者采用MethyLight技术检测CpG岛甲基化表型（CIMP）高表型。肿瘤被分配到不同的分子途径，并检查临床病理相关性和生存分析。传统途径占33.4%的CRC病例，交替途径占11.6%，锯齿状分子途径仅占中东CRC病例的0.8%。大约54.2%的CRC病例不符合任何途径，因此被指定为未分配组。发现分子途径与肿瘤部位和分级显著相关。一个子集的情况下，一个未分类的途径表现出显着的生存差异（P = 0.0079）。CONCLUSIONSTTHE锯齿状的途径被发现占一个非常低的百分比CRC患者队列在目前的研究。未分配组占中东CRC病例的大多数，因此CRC途径分析方法可能不适用于该种族组。目前的研究表明，需要解开这种疾病的分子遗传基础，以进一步对这些CRC病例进行亚分类。它还确定需要对不同人群进行进一步研究，以更好地了解其确切作用和发生率。Cancer 2015;121：3799-3808. (c)2015年美国癌症协会。目前的研究结果表明，需要解开结直肠癌的分子遗传基础，以进一步对结直肠癌病例进行亚分类。他们还强调需要对不同人群进行进一步研究，以更好地了解遗传途径的确切作用和发生率。
BACKGROUNDColorectal cancer (CRC) is one of the most common cancers in the world. A newly proposed integrated pathway comprising traditional, alternate, and serrated pathways by genetic and epigenetic factors was defined recently and hypothesized to play a role in the pathogenesis of CRC; however, to the authors' knowledge, there is a paucity of information regarding these proposed molecular pathways in different ethnic groups.METHODSMolecular characterization of 770 CRC specimens was performed for microsatellite instability, BRAF, and KRAS by polymerase chain reaction and 500 cases for CpG island methylator phenotype (CIMP) high phenotype by MethyLight technology. Tumors were assigned to different molecular pathways and examined for clinicopathological correlation and survival analysis.RESULTSThe traditional pathway constituted 33.4% of CRC cases, the alternate pathway comprised 11.6%, and the serrated molecular pathway accounted for only 0.8% of Middle Eastern CRC cases. Approximately 54.2% of CRC cases did not qualify to fit into any pathway and thus were designated as an unassigned group. Molecular pathways were found to be significantly associated with tumor site and grade. A subset of cases with an uncategorized pathway demonstrated a significant survival difference (P = .0079).CONCLUSIONSThe serrated pathway was found to account for a very low percentage of the CRC patient cohort in the current study. The unassigned group accounted for the majority of Middle Eastern CRC cases, and therefore methods of CRC pathway analysis might not be applicable to this ethnic group. The current study demonstrates the need to unravel the molecular genetic basis of this disease to further subcategorize these CRC cases. It also identifies a need for further studies on different populations for a better understanding of their exact role and incidence. Cancer 2015;121:3799-3808. (c) 2015 American Cancer Society.The results of the current study indicate the need to unravel the molecular genetic basis of colorectal carcinoma to further subcategorize colorectal carcinoma cases. They also emphasize the need to perform further studies on different populations to develop a better understanding of the exact role and incidence of genetic pathways.