Identification of Immunization-related New Prognostic Biomarkers for Papillary Renal Cell Carcinoma by Integrated Bioinformatics Analysis

Overview

Journal BMC Med Genomics

Publisher Biomed Central

Specialty Genetics

Date 2021 Oct 8

PMID 34620162

Citations 4

Authors

Ping Wu

Tingting Xiang

Jing Wang

Run Lv

Shaoxin Ma

Limei Yuan

Guangzhen Wu

Xiangyu Che

Affiliations

Soon will be listed here.

Abstract

Background: Despite papillary renal cell carcinoma (pRCC) being the second most common type of kidney cancer, the underlying molecular mechanism remains unclear. Targeted therapies in the past have not been successful because of the lack of a clear understanding of the molecular mechanism. Hence, exploring the underlying mechanisms and seeking novel biomarkers for pursuing a precise prognostic biomarker and appropriate therapies are critical.

Material And Methods: In our research, the differentially expressed genes (DEGs) were screened from the TCGA and GEO databases, and a total of 149 upregulated and 285 downregulated genes were sorted. This was followed by construction of functional enrichment and protein-protein interaction (PPI) network, and then the top 15 DEGs were selected for further analysis. The P4HB gene was chosen as our target gene by repetitively validating multiple datasets, and higher levels of P4HB expression predicted lower overall survival (OS) in patients with pRCC.

Results: We found that P4HB not only connects with immune cell infiltration and co-expression with PD-1, PD-L2, and CTLA-4, but also has a strong connection with the newly discovered hot gene, TOX.

Conclusion: We speculate that P4HB is a novel gene involved in the progression of pRCC through immunomodulation.

Citing Articles

Obesity-Dependent Association of the rs10454142 with Breast Cancer.

Ponomarenko I, Pasenov K, Churnosova M, Sorokina I, Aristova I, Churnosov V Biomedicines. 2024; 12(4).

PMID: 38672173 PMC: 11048332. DOI: 10.3390/biomedicines12040818.

Targeting Prolyl 4-Hydroxylase Subunit Beta (P4HB) in Cancer: New Roads to Travel.

Feng D, Wang J, Li D, Wu R, Tuo Z, Yu Q Aging Dis. 2023; 15(6):2369-2380.

PMID: 38029391 PMC: 11567247. DOI: 10.14336/AD.2023.1126.

Prolyl 4-hydroxylase subunit beta (P4HB) could serve as a prognostic and radiosensitivity biomarker for prostate cancer patients.

Feng D, Li L, Li D, Wu R, Zhu W, Wang J Eur J Med Res. 2023; 28(1):245.

PMID: 37480146 PMC: 10362756. DOI: 10.1186/s40001-023-01215-2.

Identification and validation of P4HB as a novel autophagy-related biomarker in diabetic nephropathy.

Bai F, Yu K, Yang Y, Zhang Y, Ding L, An X Front Genet. 2022; 13:965816.

PMID: 36226178 PMC: 9548632. DOI: 10.3389/fgene.2022.965816.

References

Liao Y, Wang J, Jaehnig E, Shi Z, Zhang B . WebGestalt 2019: gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 2019; 47(W1):W199-W205. PMC: 6602449. DOI: 10.1093/nar/gkz401. View

Jones J, Otu H, Spentzos D, Kolia S, Inan M, Beecken W . Gene signatures of progression and metastasis in renal cell cancer. Clin Cancer Res. 2005; 11(16):5730-9. DOI: 10.1158/1078-0432.CCR-04-2225. View

Goodall G, Wickramasinghe V . RNA in cancer. Nat Rev Cancer. 2020; 21(1):22-36. DOI: 10.1038/s41568-020-00306-0. View

Zheng H, Takahashi H, Li X, Hara T, Masuda S, Guan Y . Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas. Hum Pathol. 2008; 39(7):1042-9. DOI: 10.1016/j.humpath.2007.11.009. View

Ruscica M, Dozio E, Boghossian S, Bovo G, Martos Riano V, Motta M . Activation of the Y1 receptor by neuropeptide Y regulates the growth of prostate cancer cells. Endocrinology. 2005; 147(3):1466-73. DOI: 10.1210/en.2005-0925. View

Szklarczyk D, Gable A, Lyon D, Junge A, Wyder S, Huerta-Cepas J . STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2018; 47(D1):D607-D613. PMC: 6323986. DOI: 10.1093/nar/gky1131. View

Korner M, Waser B, Reubi J . High expression of neuropeptide Y1 receptors in ewing sarcoma tumors. Clin Cancer Res. 2008; 14(16):5043-9. DOI: 10.1158/1078-0432.CCR-07-4551. View

Todd D, Lee A, Glimcher L . The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol. 2008; 8(9):663-74. DOI: 10.1038/nri2359. View

Yusenko M, Kuiper R, Boethe T, Ljungberg B, Geurts van Kessel A, Kovacs G . High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas. BMC Cancer. 2009; 9:152. PMC: 2686725. DOI: 10.1186/1471-2407-9-152. View

10.

Smoot M, Ono K, Ruscheinski J, Wang P, Ideker T . Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2010; 27(3):431-2. PMC: 3031041. DOI: 10.1093/bioinformatics/btq675. View

11.

Okadome K, Baba Y, Nomoto D, Yagi T, Kalikawe R, Harada K . Prognostic and clinical impact of PD-L2 and PD-L1 expression in a cohort of 437 oesophageal cancers. Br J Cancer. 2020; 122(10):1535-1543. PMC: 7217865. DOI: 10.1038/s41416-020-0811-0. View

12.

Scott A, Dundar F, Zumbo P, Chandran S, Klebanoff C, Shakiba M . TOX is a critical regulator of tumour-specific T cell differentiation. Nature. 2019; 571(7764):270-274. PMC: 7698992. DOI: 10.1038/s41586-019-1324-y. View

13.

Langer R, Feith M, Siewert J, Wester H, Hoefler H . Expression and clinical significance of glucose regulated proteins GRP78 (BiP) and GRP94 (GP96) in human adenocarcinomas of the esophagus. BMC Cancer. 2008; 8:70. PMC: 2270853. DOI: 10.1186/1471-2407-8-70. View

14.

LaDuca H, Stuenkel A, Dolinsky J, Keiles S, Tandy S, Pesaran T . Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients. Genet Med. 2014; 16(11):830-7. PMC: 4225457. DOI: 10.1038/gim.2014.40. View

15.

Harjunpaa H, Llort Asens M, Guenther C, Fagerholm S . Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment. Front Immunol. 2019; 10:1078. PMC: 6558418. DOI: 10.3389/fimmu.2019.01078. View

16.

Robertson-Tessi M, Gillies R, Gatenby R, Anderson A . Impact of metabolic heterogeneity on tumor growth, invasion, and treatment outcomes. Cancer Res. 2015; 75(8):1567-79. PMC: 4421891. DOI: 10.1158/0008-5472.CAN-14-1428. View

17.

Lv X, Zhao F, Huo X, Tang W, Hu B, Gong X . Neuropeptide Y1 receptor inhibits cell growth through inactivating mitogen-activated protein kinase signal pathway in human hepatocellular carcinoma. Med Oncol. 2016; 33(7):70. DOI: 10.1007/s12032-016-0785-1. View

18.

Yuan K, Ye J, Liu Z, Ren Y, He W, Xu J . Complement C3 overexpression activates JAK2/STAT3 pathway and correlates with gastric cancer progression. J Exp Clin Cancer Res. 2020; 39(1):9. PMC: 6956509. DOI: 10.1186/s13046-019-1514-3. View

19.

Kobayashi M, Nagashio R, Jiang S, Saito K, Tsuchiya B, Ryuge S . Calnexin is a novel sero-diagnostic marker for lung cancer. Lung Cancer. 2015; 90(2):342-5. DOI: 10.1016/j.lungcan.2015.08.015. View

20.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View