Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis.
Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis.
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DOI：
10.1016/j.tranon.2018.07.008
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发表时间：
2018-10
影响因子：
5
通讯作者：
Kopetz S
中科院分区：
文献类型：
--
作者：
Advani SM;Advani P;DeSantis SM;Brown D;VonVille HM;Lam M;Loree JM;Mehrvarz Sarshekeh A;Bressler J;Lopez DS;Daniel CR;Swartz MD;Kopetz S
背景：CpG岛甲基化表型(CIMP)肿瘤占结直肠癌的20%，与女性性别、年龄、右侧位置和BRAF突变有关。然而，其他可能与CIMP相关的因素尚未得到有力的研究。这一荟萃分析提供了对定义CIMP肿瘤的临床、病理和分子特征的全面评估。方法：我们对1999年1月至2018年4月的文献进行了全面的检索，确定了122篇文章，对CIMP亚组的临床、病理、分子和突变特征进行了全面的数据提取，根据各种实验室方法评估的抑癌基因的DNA甲基化程度进行了分类。CIMP与预后参数的相关性使用合并优势比或使用随机效应模型的标准化均值差异来评估。结果：我们确认了先前的相关因素，包括女性、高龄、右侧肿瘤位置、低分化和微卫星不稳定性。除了已知与BRAF突变相关外，CIMP还与PIK3CA突变以及KRAS和TP53中缺乏突变相关。免疫反应被激活的证据是高比率的肿瘤浸润性淋巴细胞(但不是瘤周淋巴细胞)、克罗恩样浸润物和核梭杆菌的浸润性。此外，CIMP肿瘤与晚期T分期、神经周围和淋巴血管侵犯有关。结论：Meta分析强调了结直肠癌中CIMP的主要特征，包括主动免疫反应的分子特征。对结直肠癌这种独特的分子亚型的更好的理解可能会为预防和治疗提供洞察力。
BACKGROUND: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model. RESULTS: We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion. CONCLUSION: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.
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影响因子：
3.8
作者：
Ang PW;Loh M;Liem N;Lim PL;Grieu F;Vaithilingam A;Platell C;Yong WP;Iacopetta B;Soong R
通讯作者：
Soong R
影响因子：
3.5
作者：
Bae, Jeong Mo;Kim, Mi Jung;Kang, Gyeong Hoon
通讯作者：
Kang, Gyeong Hoon
影响因子：
9.7
作者：
Ang, Pei Woon;Li, Wei Qi;Iacopetta, Barry
通讯作者：
Iacopetta, Barry
影响因子：
6.2
作者：
Beg, Shaham;Siraj, Abdul K.;Al-Kuraya, Khawla S.
通讯作者：
Al-Kuraya, Khawla S.
DNA甲基化可预测切除的III期近端结肠癌的复发。
影响因子：
6.2
作者：
Ahn, Joong Bae;Chung, Woon Bok;Maeda, Osamu;Shin, Sang Joon;Kim, Hyun Soo;Chung, Hyun Chul;Kim, Nam Kyu;Issa, Jean-Pierre J.
通讯作者：
Issa, Jean-Pierre J.