Potential Impact of Cancer Susceptibility Genes on Lung Cancer Metastasis

Abstract

Background. 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. Methods. 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. Results. 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 $\left(\text{HR}\right)=1.076$ , 95% confidence interval $\left(\text{CI}\right)=1.049$ –1.103, $P<0.001$ ; multivariate: $\text{HR}=1.066$ , 95% $\text{CI}=1.037$ –1.095, $P<0.001$ ) and LUSC survival (univariate: $\text{HR}=1.149$ , 95% $\text{CI}=1.066$ −1.239, $P<0.001$ ; multivariate: $\text{HR}=1.129$ , 95% $\text{CI}=1.038$ −1.228, $P=0.005$ ). One of the processes affected by differentially expressed genes in both LUAD and LUSC was the negative regulation of epithelial cell differentiation. Conclusions. 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.