Integrative genomic profiling reveals characteristics of lymph node metastasis in small cell lung cancer.

BACKGROUND

Small cell lung cancer (SCLC) is the most aggressive lung cancer subtype, with more than 70% of patients having metastatic disease and a poor prognosis. However, no integrated multi-omics analysis has been performed to explore novel differentially expressed genes (DEGs) or significantly mutated genes (SMGs) associated with lymph node metastasis (LNM) in SCLC.

METHODS

In this study, whole-exome sequencing (WES) and RNA-sequencing were performed on tumor specimens to investigate the association between genomic and transcriptome alterations and LNM in SCLC patients with (N+, n=15) or without (N0, n=11) LNM.

RESULTS

The results of WES revealed that the most common mutations occurred in (85%) and (81%). The SMGs, including and , were associated with LNM. Cosmic signature analysis showed that mutation signatures 2, 4, and 7 were associated with LNM. Meanwhile, DEGs, including and , were found to be associated with LNM. Furthermore, we found that the messenger RNA (mRNA) levels of (P=0.0087), (P=0.058), (P=0.05), and (P=0.042) were significantly correlated with copy number variants (CNVs), and expression was consistently lower in N+ tumors than in N0 tumors. Further validation in cBioPortal revealed a significant correlation between LNM and poor prognosis in SCLC (P=0.014), although there was no significant correlation between LNM and overall survival (OS) in our cohort (P=0.75).

CONCLUSIONS

To our knowledge, this is the first integrative genomics profiling of LNM in SCLC. Our findings are particularly important for early detection and the provision of reliable therapeutic targets.