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A Novel Pancreatic Cancer Hypoxia Status Related Gene Signature for Prognosis and Therapeutic Responses

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Abstract

Pancreatic cancer (PAC) is a highly fatal and aggressive type of cancer. Hypoxia is a common feature of PAC. The aim of this study was to develop a hypoxia status-related prognostic model for predicting the survival outcomes in PAC. The data sets of PAC from The Cancer Genome Atlas and the International Cancer Genome Consortium were used to construct and validate the signature. A 6 hypoxia status-related differential expression genes prognostic model for predicting the survival outcomes was established. The Kaplan–Meier analysis and Received operating characteristic curve indicated the good performance of the signature at predicting overall survival. Univariate and Multivariate Cox regression revealed that the signature was an independent prognostic factor in PAC. Weighted Gene Co-expression Network Analysis and immune infiltration analysis indicated that Immune-related pathways and immune cell infiltration was mostly enriched in the low-risk group, which presented a better prognosis. We also evaluated the predictive of the signature for immunotherapy and chemoradiotherapy. Risk gene LY6D may be a potential prognostic predictor of PAC. This model can be used as an independent prognostic factor for predicting clinical outcomes and a possible classifier for response to chemotherapy.

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Data Availability

The mRNA-seq transcriptome profiling and corresponding clinical data of PAC patients for the training set (TCGA database, https://portal.gdc.cancer.gov/repository) and validation set (ICGC database, https://dcc.icgc.org/) were downloaded from UCSC Xena (https://xenabrowser.net/datapages/).

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Funding

This study was supported by the Scientific research plan project of Shaanxi Provincial Department of Education (21JK0993).

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Authors and Affiliations

  1. College of Life Science, Yan’an University, Yan’an, 716000, China

    Min Ren, Jianing Zhang, Rongrong Zong & Huiru Sun

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  1. Min Ren
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  2. Jianing Zhang
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Contributions

MR and HS designed the study, wrote the manuscript, and collected the corresponding datasets. JZ, and RZ assisted in the model construction and model validation. MR and JZ drew the figures as well as tables. HS supervised the whole project and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Min Ren or Huiru Sun.

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Supplementary Information

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Figure S1. Box plot of the expression levels of the six genes used in the signature. Supplementary file1 (PDF 198 kb)

12033_2023_807_MOESM2_ESM.pdf

Figure S2. Kaplan-Meier curve of OS in PAC patients with high- and low-expression of 6 genes. Supplementary file2 (PDF 376 kb)

12033_2023_807_MOESM3_ESM.pdf

Figure S3. Association analysis between TMB and risk score (A) The association between TMB and risk score. (B) Kaplan-Meier curve of OS in PAC patients with high- and low-TMB. (C) Spearman correlation analysis between TMB and risk score. Supplementary file3 (PDF 540 kb)

Figure S4. Association between risk score and chemosensitivity in PAC. Supplementary file4 (PDF 509 kb)

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Ren, M., Zhang, J., Zong, R. et al. A Novel Pancreatic Cancer Hypoxia Status Related Gene Signature for Prognosis and Therapeutic Responses. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00807-x

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  • DOI: https://doi.org/10.1007/s12033-023-00807-x

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