Dataset Information

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

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.

SUBMITTER: Zhu Q

PROVIDER: S-EPMC11301104 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zhu Qizhi Q Fu Meng M Qi Jian J Xu Ziming Z Wang Yongguang Y Wang Zhipeng Z Wang Dan D Liu Jiajia J Du Ruiping R Wei Xin X Wang Hongzhi H Nie Jinfu J Hong Bo B Xu Weiping W

iScience 20240628 8

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 valid ...[more]

PMID: 39108724

Similar Datasets

Project description:BackgroundSmall cell lung cancer (SCLC) is a very malignant tumor with rapid growth and early metastasis. Platinum-based chemo-resistance is the major issue for SCLC treatment failure. Identifying a new prognostic model will help to make an accurate treatment decision for SCLC patients.MethodsUsing the genomics of drug sensitivity in cancer (GDSC) database, we identified cisplatin resistance-related lncRNAs in SCLC cells. Based on the competing endogenous RNA (ceRNA) network, we identified the mRNAs correlated with the lncRNAs. Using Cox and LASSO regression analysis, a prognostic model was established. The survival prediction accuracy was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier analysis. GSEA, GO, KEGG and CIBERSORT tools were used for functional enrichment and immune cells infiltration analysis.ResultsWe first screened out 10 differentially expressed lncRNAs between cisplatin resistant and sensitive SCLC cells from GDSC database. Based on ceRNA network, 31 mRNAs were identified with a correlation with the 10 lncRNAs. Furthermore, two genes (LIMK2 and PI4K2B) were identified by Cox and LASSO regression analysis to construct a prognostic model. Kaplan-Meier analysis indicated that the high-risk group had a poor overall survival compared with the low-risk group. The predicted area under the ROC curve (AUC) was 0.853 in the training set, and the AUC was 0.671 in the validation set. In the meanwhile, the low expression of LIMK2 or the high expression of PI4K2B in SCLC tumors was also significantly associated with poor overall survival in both training and validation sets. Functional enrichment analysis showed that the low-risk group was enriched in the apoptosis pathway and high immune infiltration of T cells. Finally, an apoptosis-related gene Cathepsin D (CTSD) was identified to be up-regulated in the low-risk group, and its higher expression correlated with better overall survival in SCLC.ConclusionWe established a prognostic model and potential biomarkers (LIMK2, PI4K2B and CTSD), which could help to improve the risk stratification of SCLC patients.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets