Distinguishing Lung Adenocarcinoma from Lung Squamous Cell Carcinoma by Two Hypomethylated and Three Hypermethylated Genes: A Meta-Analysis

Significant differences in the aberrant methylation of genes exist among various histological types of non-small cell lung cancer (NSCLC), which includes adenocarcinoma (AC) and squamous cell carcinoma (SCC). Different chemotherapeutic regimens should be administered to the two NSCLC subtypes due to their unique genetic and epigenetic profiles. The purpose of this meta-analysis was to generate a list of differentially methylated genes between AC and SCC. Our meta-analysis encompassed 151 studies on 108 genes among 12946 AC and 10243 SCC patients. Our results showed two hypomethylated genes (CDKN2A and MGMT) and three hypermethylated genes (CDH13, RUNX3 and APC) in ACs compared with SCCs. In addition, our results showed that the pooled specificity and sensitivity values of CDH13 and APC were higher than those of CDKN2A, MGMT and RUNX3. Our findings might provide an alternative method to distinguish between the two NSCLC subtypes.

非小细胞肺癌（non-small cell lung cancer, NSCLC）包含腺癌（adenocarcinoma, AC）与鳞状细胞癌（squamous cell carcinoma, SCC）两种组织学亚型，不同亚型的基因异常甲基化水平存在显著差异。由于这两种非小细胞肺癌亚型具有独特的遗传与表观遗传特征，因此需针对二者采用不同的化疗方案。本项荟萃分析的目的在于筛选出腺癌与鳞状细胞癌之间存在甲基化差异的基因列表。本次荟萃分析共纳入151项相关研究，涉及108个基因，涵盖12946例腺癌患者与10243例鳞状细胞癌患者。研究结果显示，与鳞状细胞癌相比，腺癌患者体内存在2个低甲基化基因（CDKN2A与MGMT）以及3个高甲基化基因（CDH13、RUNX3与APC）。此外，本研究结果表明，CDH13与APC的合并特异度及灵敏度均高于CDKN2A、MGMT及RUNX3。本研究结果可为区分这两种非小细胞肺癌亚型提供一种新的辅助手段。