Cisplatin resistance-related transcriptome and methylome integration identifies PCDHB4 as a novel prognostic biomarker in small cell lung cancer

Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of PCDHB4 was associated with poorer survival of SCLC patients who received chemotherapy. PCDHB4 gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher PCDHB4 expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with PCDHB4 expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of PCDHB4 were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, PCDHB4 is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.