Wang Jiaqing, Peng Bin, Sun Xuefeng, Ding Peikun, Li Shixuan, Li Guofeng, Shi Xiaoshun, Wang Guangsuo
Department of Thoracic Surgery, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen 518020, China.
Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China.
J Oncol. 2022 Apr 18;2022:1516946. doi: 10.1155/2022/1516946. eCollection 2022.
Studies of prognosis-related molecular markers are an important tool to uncover the mechanism of tumour metastasis. Cancer susceptibility gene testing is an important tool for genetic counselling of cancer risk. However, the impact of lung cancer susceptibility genes (LCSGs) on lung cancer metastasis and prognosis has not been well studied.
The list of lung cancer susceptibility genes was retrospectively analysed and updated. After expression profiling and functional analysis, LCSG-based signatures for prognosis were identified by Cox regression and LASSO regression analyses. For translational purposes, nomograms integrating LCSGs and clinical characteristics were constructed.
A total of 301 LCSGs were employed for modelling. For lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), 10-gene and 7-gene signatures were created and independently validated. The LCSG-based risk score could stratify LUAD survival (univariate: hazard ratio (HR) = 1.076, 95% confidence interval (CI) = 1.049-1.103, < 0.001; multivariate: HR = 1.066, 95% CI = 1.037-1.095, < 0.001) and LUSC survival (univariate: HR = 1.149, 95% CI = 1.066-1.239, < 0.001; multivariate: HR = 1.129, 95% CI = 1.038-1.228, = 0.005). One of the processes affected by differentially expressed genes in both LUAD and LUSC was the negative regulation of epithelial cell differentiation.
Overall, novel LCSG-based gene signatures for LUAD and LUSC were constructed. These findings could expand the understanding of the impact of LCSG expression on cancer metastasis and prognosis.
预后相关分子标志物的研究是揭示肿瘤转移机制的重要工具。癌症易感性基因检测是癌症风险遗传咨询的重要工具。然而，肺癌易感性基因（LCSGs）对肺癌转移和预后的影响尚未得到充分研究。
回顾性分析并更新肺癌易感性基因列表。经过表达谱分析和功能分析后，通过Cox回归和LASSO回归分析确定基于LCSG的预后特征。为了便于转化应用，构建了整合LCSGs和临床特征的列线图。
共采用301个LCSGs进行建模。针对肺腺癌（LUAD）和肺鳞癌（LUSC），分别创建了10基因和7基因特征，并进行了独立验证。基于LCSG的风险评分能够对LUAD生存情况进行分层（单因素分析：风险比（HR）=1.076，95%置信区间（CI）=1.049 - 1.103，P<0.001；多因素分析：HR = 1.066，95% CI = 1.037 - 1.095，P<0.001）以及LUSC生存情况（单因素分析：HR = 1.149，95% CI = 1.066 - 1.239，P<0.001；多因素分析：HR = 1.129，95% CI = 1.038 - 1.228，P = 0.005）。LUAD和LUSC中差异表达基因所影响的过程之一是上皮细胞分化的负调控。
总体而言，构建了基于LCSG的新型LUAD和LUSC基因特征。这些发现可能会扩展对LCSG表达对癌症转移和预后影响的理解。
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