Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Medical School, Shanghai, China.
Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai, China.
Cell Biol Toxicol. 2016 Oct;32(5):419-35. doi: 10.1007/s10565-016-9343-z. Epub 2016 Jun 15.
Lung cancer is one of the most common malignancies worldwide. The present study aimed to investigate specific genotypes of different subtypes or stages of lung cancer through gene expression variations of chromosome 2 genes, trying to identify predictors for diagnosis or prognosis of lung cancer. About 537 patients with lung adenocarcinoma (ADC), 140 patients with lung squamous carcinoma (SQC), 9 patients with lung large cell carcinoma (LCC), 56 patients with small cell lung cancer (SCLC), and 590 patients without cancer were analyzed in present study. Co-expressed, subtype-specific, and stage-specific chromosome 2 genes were identified and further analyzed by bioinformatic methods. As a result, 15 or 10 genes were significantly up- or down-regulated in all four subtypes of lung cancer. GKN1, LOC100131510, prominin-2 (PROM2), IL37, and SNORA41 were identified as ADC-specific up-regulated genes; SQC-specific up-regulated genes included HOXD family (HOXD1, HOXD3, HOXD4, HOXD8, and HOXD9) and UGT1A family (UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A7, UGT1A8, UGT1A9, and UGT1A10); and LCC- or SCLC-specific genes were also identified. Nine genes were significantly up-expressed at all four stages of ADC while 230 genes at all three stages of SQC. MFSD2B, CCL20 and STAT1, or STARD7 and ZNF512 genes may be risk or protect factors in prognosis of ADC, while HTR2B, DPP4, and TGFBRAP1 genes may be risk factors in prognosis of SQC. Our results suggested that a number of altered chromosome 2 genes have the subtype or stage specificities of lung cancer and may be considered as diagnostic and prognostic biomarkers.
肺癌是全球最常见的恶性肿瘤之一。本研究旨在通过染色体 2 基因的表达变化来研究不同亚型或阶段肺癌的特定基因型，试图确定用于肺癌诊断或预后的预测因子。本研究共分析了 537 例肺腺癌（ADC）患者、140 例肺鳞癌（SQC）患者、9 例肺大细胞癌（LCC）患者、56 例小细胞肺癌（SCLC）患者和 590 例非癌症患者。通过生物信息学方法对共表达、亚型特异性和阶段特异性的染色体 2 基因进行鉴定和进一步分析。结果显示，在所有四种肺癌亚型中，有 15 个或 10 个基因显著上调或下调。GKN1、LOC100131510、prominin-2（PROM2）、IL37 和 SNORA41 被鉴定为 ADC 特异性上调基因；SQC 特异性上调基因包括 HOXD 家族（HOXD1、HOXD3、HOXD4、HOXD8 和 HOXD9）和 UGT1A 家族（UGT1A1、UGT1A3、UGT1A4、UGT1A5、UGT1A7、UGT1A8、UGT1A9 和 UGT1A10）；还鉴定了 LCC 或 SCLC 特异性基因。在 ADC 的所有四个阶段，有 9 个基因显著上调，在 SQC 的所有三个阶段，有 230 个基因上调。MFSD2B、CCL20 和 STAT1 或 STARD7 和 ZNF512 基因可能是 ADC 预后的风险或保护因素，而 HTR2B、DPP4 和 TGFBRAP1 基因可能是 SQC 预后的风险因素。我们的研究结果表明，一些染色体 2 基因的改变具有肺癌的亚型或阶段特异性，可作为诊断和预后的生物标志物。
