Differences in small cell lung cancer genetic profile between disease progression (PD) and partial remission (PR) patients after the standard first-line chemotherapy

Author:Yalei Zhang, Yongxin Geng, Yan Hao, Hui Pan, Wenhua Liang, Jun Liu, Fei Cui, Henghui Zhang, Minghui Ge, Jianxing He

Background/Aim: Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with high malignancy, frequent metastases and poor prognosis. SCLC patients are relatively sensitive to radiotherapy and chemotherapy, which are mainly therapy in the clinical of SCLC. 

However, the puzzle in the therapy was the rapid resistance of tumor cells against chemotherapy and the failure of second-line chemotherapy. The purpose of this study was to use the accurate medical method to screen out the genes related to SCLC and the key molecular markers that are suitable for the curative effect of chemotherapy, resulting in realize the molecular prediction of small cell lung cancer. 

Patients and Methods: 24 patients with first-line treatment of SCLC receiving standard chemotherapy (EP) were included, whom were reviewed and categorized into two groups: disease progression (PD) and disease remission (PR). The tumor tissue DNA of the patients were detected by specific target gene capture sequencing technology to detect the gene variation of SCLC and bioinformatics methods were used to screen chemotherapy-related genes. 

Results: TP53, CYP2C19, ZFHX3, BCL2 are the Common gene mutations in Chinese SCLC patient population; Common Genes for Copy number variations(CNV) in Small Cell Lung Cancer in China: FDPS,SOX2,MAP2K2,PSMA8,MALAT1; The comparative analysis in patients with CNV between PD and PR groups showed EGFR gene copy number variation was detected only in the PR group, and there was a significant difference between the two groups (P <0.05, Fisher test); The tumor tissue DNA somatic cells single nucleotide variants (SNV), genotypes associated with first-line chemotherapy(EP), Tumor Mutational Burden(TMB) and Copy number instability(CNI) of tumor tissues showed no significant difference between two groups.