Dissecting the genetic variations associated with response to first-line chemotherapy in patients with small cell lung cancer: a retrospective cohort study.

BACKGROUND

Chemotherapy has been the standard treatment for small-cell lung cancer (SCLC) for decades. Nonetheless, patients are usually responsive to initial chemotherapy but quickly suffer from relapse, resulting in a poor long-term outcome. Treating advances that greatly ameliorate survival outcomes are historically finite, and credible biomarkers for therapeutic evaluation are deficient. As the genetic biology emerges, investigating biomarkers to optimize individualized treatment for SCLC is necessary.

METHODS

Based on following inclusion criteria: (I) patients diagnosed as SCLC by pathology; (II) patients treated with first-line etoposide/cisplatin (EP) chemotherapy; (III) patients who received long-term follow-up and signed informed consent, a total of 24 SCLC patients receiving first-line standard chemotherapy were divided into progressive disease (PD) and partial response (PR) groups. They were regularly followed every 3 months with computed tomography (CT) scan until recurrences determined by CT scan results. Next-generation sequencing (NGS) with a panel of 1,406 cancer-related genes was conducted on the tumor tissue-derived DNA of patients to compare genetic variations, including deletions (indels), single nucleotide variations (SNVs), copy number variations (CNVs), and copy number instability (CNI) between the two groups.

RESULTS

For the clinical characteristics of enrolled SCLC patients, except for significant differences in sex, age, clinical stage, and limited or extensive stage, PD patients showed distinctly shorter overall survival than those with PR (6.5 14.0 months, respectively, P=0.007). Genetic variations analysis discovered several common genes with CNV mutations between the PR and PD groups, and increased epidermal growth factor receptor () gene copy numbers gain was found in PR groups in comparing with PD patients (P=0.006). However, no significant differences in terms of SNVs, indels, genotypes associated with first-line chemotherapy, CNI of tumor tissue-derived DNA, and tumor mutational burden of tumor tissues were observed between two groups. Additionally, the relationship between gene mutation and clinicopathological features of SCLC indicated that gene mutation may be an independent indicator for SCLC patients.

CONCLUSIONS

Increased gene CNVs may be an independent indicator influencing the survival time and PR in SCLC patients receiving standard first-line chemotherapy.