Abstract
Purpose
Patients with pancreatic cancer (PC) can be classified into various molecular subtypes and benefit from some precise therapy. Nevertheless, the interaction between metabolic and immune subtypes in the tumor microenvironment (TME) remains unknown. We hope to identify molecular subtypes related to metabolism and immunity in pancreatic cancer
Methods
Unsupervised consensus clustering and ssGSEA analysis were utilized to construct molecular subtypes related to metabolism and immunity. Diverse metabolic and immune subtypes were characterized by distinct prognoses and TME. Afterward, we filtrated the overlapped genes based on the differentially expressed genes (DEGs) between the metabolic and immune subtypes by lasso regression and Cox regression, and used them to build risk score signature which led to PC patients was categorized into high- and low-risk groups. Nomogram were built to predict the survival rates of each PC patient. RT-PCR, in vitro cell proliferation assay, PC organoid, immunohistochemistry staining were used to identify key oncogenes related to PC
Results
High-risk patients have a better response for various chemotherapeutic drugs in the Genomics of Drug Sensitivity in Cancer (GDSC) database. We built a nomogram with the risk group, age, and the number of positive lymph nodes to predict the survival rates of each PC patient with average 1-year, 2-year, and 3-year areas under the curve (AUCs) equal to 0.792, 0.752, and 0.751. FAM83A, KLF5, LIPH, MYEOV were up-regulated in the PC cell line and PC tissues. Knockdown of FAM83A, KLF5, LIPH, MYEOV could reduce the proliferation in the PC cell line and PC organoids
Conclusion
The risk score signature based on the metabolism and immune molecular subtypes can accurately predict the prognosis and guide treatments of PC, meanwhile, the metabolism-immune biomarkers may provide novel target therapy for PC
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Data availability
All data generated or analyzed during this study can be downloaded from TCGA (https://portal.gdc.cancer.gov/), GTEx (https://www.gtexportal.org/home), and ICGC (https://icgc.org).
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Acknowledgements
Thanks to all who have contributed to the process of my writing this article. Especially, thanks to my girlfriend NR P who supported me in my life. At last, I’d like to thank those leaders, teachers, and my families who have encouraged me.
Funding
This study was supported by grants from the National Natural Science Foundation of China (No.81972258, No.81974376, No. 82103016, No. 82172836, No.82272917); Natural Science Foundation of Beijing (No. 7192157); CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-1-I2M-002); National Key R&D Program of China (2018YFE0118600); National High Level Hospital Clinical Research Funding 2022-PUMCH-D-001; China Postdoctoral Science Foundation (2021T140071 and 2021M690462), Youth Research Fund of Peking Union Medical College Hospital (pumch201911710, pumch201910819), National High Level Hospital Clinical Research Funding 2022-PUMCH-A-245, National High Level Hospital Clinical Research Funding 2022-PUMCH-A-056, and Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018PT32014).
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GC analyzed the data and wrote the manuscript. TZ and YZ conceived the study and obtained financial support. , YL, DS, JL applied guiding suggestions, GY, JQ, FZ, JT,HH,XJ prepared the dataset. All authors read and approved the final manuscript.
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Chen, G., Liu, Y., Su, D. et al. Genomic analysis and filtration of novel prognostic biomarkers based on metabolic and immune subtypes in pancreatic cancer. Cell Oncol. 46, 1691–1708 (2023). https://doi.org/10.1007/s13402-023-00836-3
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DOI: https://doi.org/10.1007/s13402-023-00836-3