Identification of Molecular Biomarkers Associated with Non-Small-Cell Lung Carcinoma (NSCLC) Using Whole-Exome Sequencing Analysis

Significant advancement has been made in the treatment of patients with on the basis of the molecular profile. However, no such molecular target exists for squamous cell carcinoma (SQCC). Whole-exome sequencing (WES) has been in wide use for the discovery of new genetic pulmonary adenocarcinoma (ADCA) markers, which may offer more information for the development of personalized medicine for all subtypes of lung cancer. The aim of the current study is to find out novel genetic markers for non-small-cell lung carcinoma (NSCLC). WES of 19 advanced NSCLC patients (10 ADCA and 9 SQCC) was done on the Illumina HiSeq 2000 (Illumina Inc., USA). Variant calling was performed using GATK HaplotypeCaller and subsequent the impacts of variants on protein structure or function were predicted using SnpEff and ANNOVAR. Clinical impact of variants was evaluated using cancer-related archives. Somatic variants were further prioritized using knowledge-driven variant interpretation approach. Functionally important variants were validated by Sanger sequencing. We identified 24 rare single-nucleotide variants (SNVs) including 17 non-synonymous SNVs, and 7 INDELs in 18 genes possibly linked to lung carcinoma. Sanger sequencing of 10 high confidence somatic SNVs showed 100% concordance in 7 genes, whereas 80% in the remaining 3 genes. Our bioinformatics analysis identified KCNJ18, GPRIN2, TEKT4, HRNR, FOLR3, ESSRA, CTBP2, MPRIP, TBP, and FBXO6 may contribute to progression in NSCLC and could be used as new biomarkers for the treatment. Although the mechanism of GPRIN2, KCNJ12 and TEKT4 in tumorigenesis is unclear; our results suggest that these may play a major role in NSCLC and it is worth investigating in future.