Investigation of Underlying Biological Association and Targets Between Rejection of Renal Transplant and Renal Cancer

Overview

Journal Int J Genomics

Publisher Wiley

Date 2023 Jun 1

PMID 37261105

Authors

Yinwei Chen

Zhanpeng Liu

Qian Yu

Xu Sun

Shuai Wang

Qingyi Zhu

Jian Yang

Rongjiang Jiang

Affiliations

Soon will be listed here.

Abstract

Background: Post-renal transplant patients have a high likelihood of developing renal cancer. However, the underlying biological mechanisms behind the development of renal cancer in post-kidney transplant patients remain to be elucidated. Therefore, this study aimed to investigate the underlying biological mechanism behind the development of renal cell carcinoma in post-renal transplant patients.

Methods: Next-generation sequencing data and corresponding clinical information of patients with clear cell renal cell carcinoma (ccRCC) were obtained from The Cancer Genome Atlas Program (TCGA) database. The microarray data of kidney transplant patients with or without rejection response was obtained from the Gene Expression Omnibus (GEO) database. In addition, statistical analysis was conducted in R software.

Results: We identified 55 upregulated genes in the transplant patients with rejection from the GEO datasets (GSE48581, GSE36059, and GSE98320). Furthermore, we conducted bioinformatics analyses, which showed that all of these genes were upregulated in ccRCC tissue. Moreover, a prognosis model was constructed based on four rejection-related genes, including , , , and . The prognosis model showed excellent performance in prognosis prediction in a ccRCC cohort. In addition, the machine learning algorithms identified 19 rejection-related genes, including , involved in ccRCC occurrence. Finally, the was selected for further research, including its clinical and biological role.

Conclusion: In all, our study provides novel insight into the transition from the rejection of renal transplant to renal cancer. Meanwhile, could be a potential biomarker for ccRCC diagnosis and prognosis in post-kidney transplant patients.

References

Zhang T, Zhou X, Zhang X, Ren X, Wu J, Wang Z . Gut microbiota may contribute to the postnatal male reproductive abnormalities induced by prenatal dibutyl phthalate exposure. Chemosphere. 2021; 287(Pt 1):132046. DOI: 10.1016/j.chemosphere.2021.132046. View

Crespo M, Llinas-Mallol L, Redondo-Pachon D, Butler C, Gimeno J, Perez-Saez M . Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection. Front Immunol. 2021; 12:703457. PMC: 8300190. DOI: 10.3389/fimmu.2021.703457. View

Kinsey C, Balakrishnan V, ODell M, Huang J, Newman L, Whitney-Miller C . Plac8 links oncogenic mutations to regulation of autophagy and is critical to pancreatic cancer progression. Cell Rep. 2014; 7(4):1143-55. PMC: 4112575. DOI: 10.1016/j.celrep.2014.03.061. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Shuch B, Amin A, Armstrong A, Eble J, Ficarra V, Lopez-Beltran A . Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity. Eur Urol. 2014; 67(1):85-97. DOI: 10.1016/j.eururo.2014.04.029. View

Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V . Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016; 27(suppl 5):v58-v68. DOI: 10.1093/annonc/mdw328. View

Ren X, Zhang T, Chen X, Wei X, Tian Y, Li G . Early-life exposure to bisphenol A and reproductive-related outcomes in rodent models: a systematic review and meta-analysis. Aging (Albany NY). 2020; 12(18):18099-18126. PMC: 7585097. DOI: 10.18632/aging.103620. View

Mao M, Chen Y, Yang J, Cheng Y, Xu L, Ji F . Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer. J Immunother Cancer. 2022; 10(12). PMC: 9772693. DOI: 10.1136/jitc-2022-005668. View

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A . ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25(8):1091-3. PMC: 2666812. DOI: 10.1093/bioinformatics/btp101. View

10.

Shi L, Xiao L, Heng B, Mo S, Chen W, Su Z . Overexpression of placenta specific 8 is associated with malignant progression and poor prognosis of clear cell renal cell carcinoma. Int Urol Nephrol. 2017; 49(7):1165-1176. DOI: 10.1007/s11255-017-1578-y. View

11.

von Mering C, Huynen M, Jaeggi D, Schmidt S, Bork P, Snel B . STRING: a database of predicted functional associations between proteins. Nucleic Acids Res. 2003; 31(1):258-61. PMC: 165481. DOI: 10.1093/nar/gkg034. View

12.

Rissoan M, Duhen T, Bridon J, Bendriss-Vermare N, Peronne C, de Saint Vis B . Subtractive hybridization reveals the expression of immunoglobulin-like transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells. Blood. 2002; 100(9):3295-303. DOI: 10.1182/blood-2002-02-0638. View

13.

Salem F, Perin L, Sedrakyan S, Angeletti A, Ghiggeri G, Coccia M . The spatially resolved transcriptional profile of acute T cell-mediated rejection in a kidney allograft. Kidney Int. 2021; 101(1):131-136. PMC: 9387544. DOI: 10.1016/j.kint.2021.09.004. View

14.

Rini B, Campbell S, Escudier B . Renal cell carcinoma. Lancet. 2009; 373(9669):1119-32. DOI: 10.1016/S0140-6736(09)60229-4. View

15.

Tung K, Wu Y, Liu C, Lin S, Wu C, Wu S . EBV Rta-induced IL-6 Promotes Migration of Bystander Tumor Cells Through IL-6R/JAK/STAT3 Pathway . Anticancer Res. 2020; 40(6):3255-3264. DOI: 10.21873/anticanres.14307. View

16.

Eggers H, Guler F, Ehlers U, Ivanyi P, Peters I, Grunwald V . Renal cell carcinoma in kidney transplant recipients: descriptive analysis and overview of a major German transplant center. Future Oncol. 2019; 15(32):3739-3750. DOI: 10.2217/fon-2019-0397. View

17.

Li C, Ma H, Wang Y, Cao Z, Graves-Deal R, Powell A . Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer. J Clin Invest. 2014; 124(5):2172-87. PMC: 4001536. DOI: 10.1172/JCI71103. View

18.

Deo R . Machine Learning in Medicine. Circulation. 2015; 132(20):1920-30. PMC: 5831252. DOI: 10.1161/CIRCULATIONAHA.115.001593. View

19.

Pan M, Wang H, Ansari K, Li X, Sun W, Fan Y . Correction to: Gallbladder cancer-associated fibroblasts promote vasculogenic mimicry formation and tumor growth in gallbladder cancer via upregulating the expression of NOX4, a poor prognosis factor, through IL-6-JAK-STAT3 signal pathway. J Exp Clin Cancer Res. 2021; 40(1):236. PMC: 8286610. DOI: 10.1186/s13046-021-02014-5. View

20.

Galaviz-Hernandez C, Stagg C, de Ridder G, Tanaka T, Ko M, Schlessinger D . Plac8 and Plac9, novel placental-enriched genes identified through microarray analysis. Gene. 2003; 309(2):81-9. DOI: 10.1016/s0378-1119(03)00508-0. View