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Development and validation of a gene signature for pancreatic cancer: based on inflammatory response–related genes

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Abstract

Pancreatic cancer (PC) is one of the most common malignant tumors in the world with a poor prognosis. There were limited studies investigating the genetic signatures associated with inflammatory responses, tumor microenvironment (TME), and tumor drug sensitivity prediction. In the Cancer Genome Atlas (TCGA) dataset, we constructed an inflammatory response–related genes prognostic signature for PC, and predictive ability of the model was assessed via the International Cancer Genome Consortium (ICGC) database. Then, we explored the differences of TME, immune checkpoint genes and drug resistance genes, and the cancer cell sensitivity to chemotherapy drugs between different risk score group. Based on the TCGA and ICGC databases, we constructed and validated a prognostic model, which consisted of 5 genes (including AHR, F3, GNA15, IL18, and INHBA). Moreover, the prognostic model was independent prognostic factors affecting overall survival (OS). The low-risk score group had better OS, and lower stromal score, compared with patients in the high-risk score group. The difference of antigen-presenting cells, T cell regulation, and drug resistance genes between different risk score groups was found. In addition, the immune checkpoint genes were positively correlation to risk score. The expression levels of AHR, GNA15, IL18, and INHBA were related to the sensitivity of anti-tumor chemotherapy drugs. Gene set enrichment analysis (GSEA) showed significant pathway such as calcium signaling pathway and p53 signaling pathway. We successfully constructed a 5-inflammatory response–related gene signature to predict survival, TME, and cancer cell sensitivity to chemotherapy drugs in PC patients. Furthermore, substantiation was warranted to verify the role of these genes in tumorigenesis.

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Data availability

The datasets analyzed for this study were obtained from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) and International Cancer Genome Consortium (ICGC) (https://icgc.org/).

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Acknowledgements

We thank the Department of Hepatobiliary and Pancreatic Surgery, WeiFang People’s Hospital.

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Authors and Affiliations

  1. Department of Hepatobiliary & Pancreatic Surgery, Weifang People’s Hospital, No. 151 of Guangwen Street, Weifang, 261041, Shandong Province, People’s Republic of China

    Manjiang Li, Wei Ding, Yuxu Wang, Yongbiao Ma & Futian Du

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  1. Manjiang Li
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  2. Wei Ding
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  3. Yuxu Wang
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  4. Yongbiao Ma
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Contributions

All authors contributed to the study conception and design. Manjiang Li wrote the article. Yuxu Wang and Yongbiao Ma processed the data analysis. Wei Ding and Futian Du designed the study and reviewed the article.

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Correspondence to Futian Du.

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Supplementary information

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11356_2022_23252_MOESM1_ESM.pdf

Supplementary file1 Correlation analysis between inflammatory response‑related signature and the expression levels of immune checkpoint molecules. (A, B) PD-1. (C, D) PD-L1. (E, F) PD-L2. (G, H) CTLA-4. PD-1, programmed cell death 1; PD-L1, programmed cell death-ligand 1; PD-L2, programmed cell death-ligand 2; CTLA-4, Cytotoxic T Lymphocyte antigen 4. (PDF 995 KB)

11356_2022_23252_MOESM2_ESM.pdf

Supplementary file2 Wilcox test test and correlation analysis between inflammatory response‑related signature and the expression levels of tumor resistance genes. (A, B) MRP1. (C, D) MRP2. (E, F) MRP3. (G, H) MRP4. (I, J) MRP8. (PDF 1110 KB)

11356_2022_23252_MOESM3_ESM.pdf

Supplementary file3 Correlation analysis between prognostic model and the expression levels of tumor resistance genes. (A, B) MRP5. (C, D) MRP6. (E, F) MRP7. (G, H) MRP9. (PDF 971 KB)

Supplementary file4 (TXT 1 KB)

Supplementary file5 (TXT 71 KB)

Supplementary file6 (TXT 2 KB)

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Li, M., Ding, W., Wang, Y. et al. Development and validation of a gene signature for pancreatic cancer: based on inflammatory response–related genes. Environ Sci Pollut Res 30, 17166–17178 (2023). https://doi.org/10.1007/s11356-022-23252-w

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