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

Qizhi Zhu; Meng Fu; Jian Qi; Ziming Xu; Yongguang Wang; Zhipeng Wang; Dan Wang; Jiajia Liu; Ruiping Du; Xin Wei; Hongzhi Wang; Jinfu Nie; Bo Hong; Weiping Xu

doi:10.1016/j.isci.2024.110413

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

iScience. 2024 Jun 28;27(8):110413. doi: 10.1016/j.isci.2024.110413. eCollection 2024 Aug 16.

Authors

Qizhi Zhu^{1

2}, Meng Fu^{1

2

3}, Jian Qi^{1

2

3}, Ziming Xu², Yongguang Wang³, Zhipeng Wang^{1

2

3}, Dan Wang², Jiajia Liu², Ruiping Du³, Xin Wei^{1

2}, Hongzhi Wang^{1

3}, Jinfu Nie^{1

3}, Bo Hong^{1

3}, Weiping Xu^{1

2

4}

Affiliations

¹ Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, P.R. China.
² University of Science and Technology of China, Hefei, Anhui, P.R. China.
³ Hefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, P.R. China.
⁴ Department of Geriatrics, Gerontology Institute of Anhui Province, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China.

Abstract

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.

Keywords: cancer; cancer systems biology; transcriptomics.