Identification of 5 Gene Signatures in Survival Prediction for Patients with Lung Squamous Cell Carcinoma Based on Integrated Multiomics Data Analysis

Abstract EN

Background.

Lung squamous cell carcinoma (LSCC) is a frequently diagnosed cancer worldwide, and it has a poor prognosis.

The current study is aimed at developing the prediction of LSCC prognosis by integrating multiomics data including transcriptome, copy number variation data, and mutation data analysis, so as to predict patients’ survival and discover new therapeutic targets.

Methods.

RNASeq, SNP, CNV data, and LSCC patients’ clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA), and the samples were randomly divided into two groups, namely, the training set and the validation set.

In the training set, the genes related to prognosis and those with different copy numbers or with different SNPs were integrated to extract features using random forests, and finally, robust biomarkers were screened.

In addition, a gene-related prognostic model was established and further verified in the test set and GEO validation set.

Results.

We obtained a total of 804 prognostic-related genes and 535 copy amplification genes, 621 copy deletions genes, and 388 significantly mutated genes in genomic variants; noticeably, these genomic variant genes were found closely related to tumor development.

A total of 51 candidate genes were obtained by integrating genomic variants and prognostic genes, and 5 characteristic genes (HIST1H2BH, SERPIND1, COL22A1, LCE3C, and ADAMTS17) were screened through random forest feature selection; we found that many of those genes had been reported to be related to LSCC progression.

Cox regression analysis was performed to establish 5-gene signature that could serve as an independent prognostic factor for LSCC patients and can stratify risk samples in training set, test set, and external validation set (p<0.01), and the 5-year survival areas under the curve (AUC) of both training set and validation set were > 0.67.

Conclusion.

In the current study, 5 gene signatures were constructed as novel prognostic markers to predict the survival of LSCC patients.

The present findings provide new diagnostic and prognostic biomarkers and therapeutic targets for LSCC treatment.