PTP4A3 Is a Prognostic Biomarker Correlated With Immune Infiltrates in Papillary Renal Cell Carcinoma

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Oct 11

PMID 34630392

Citations 4

Authors

Qian Song

Yutian Zheng

Junzhou Wu

Sheng Wang

Lin Meng

Qian Yao

Zhongwu Li

Shenyi Lian

Affiliations

Soon will be listed here.

Abstract

PTP4A3 plays an important role in the tumorigenesis and metastasis of multiple tumors, but its prognostic role in renal cancer is not well understood. We utilized the Oncomine and Tumor Immunoassay Resource databases to examine the differential expression of PTP4A3 in tumor tissues and normal tissues in breast, urinary tract, gastrointestinal tract and skin. Using the GEPIA and PrognoScan databases, the independent prognostic role of PTP4A3 was confirmed in clear cell renal cell cancer and papillary renal cell cancer. Expression of PTP4A3 were obviously higher in tumor tissue compare with normal tissues (=0.028). We haven't found the associations of PTP4A3 and clinicopathological features in our IHC cohort. Ectopic expression of PTP4A3 promotes proliferation, migration and invasion and increased the mRNA level of TGFB1 in RCC cell lines. Immunohistochemical staining indicated that the expression of PTP4A3 associates with CD3+ ( =0.037)/CD8+ ( =0.037) intratumor TILs, not with invasive margins in renal cancer. Comprehensive analysis of immune infiltration in the TIMER database correlated PTP4A3 expression with the infiltration of B cells, CD8+ T cells, CD4+ T cells and neutrophils in both clear cell renal cell carcinoma and papillary renal cell carcinoma. PTP4A3 expression was associated with the infiltration of dendritic cells in papillary renal cell carcinoma. We further confirmed that the infiltration of B cells and CD8+ T cells was associated with poor prognosis in papillary renal cell carcinoma patients, consistent with the prognostic role of PTP4A3 in papillary renal cell carcinoma. PTP4A3 expression correlated genes involved in B cells, monocytes, M1 macrophages, Th2 and Treg cells in papillary renal cell carcinoma. These results suggest PTP4A3 as a prognostic factor with a role in regulating immune cell infiltration in papillary renal cell carcinoma.

Citing Articles

Protein Tyrosine Phosphatase PRL-3: A Key Player in Cancer Signaling.

Liu H, Li X, Shi Y, Ye Z, Cheng X Biomolecules. 2024; 14(3).

PMID: 38540761 PMC: 10967961. DOI: 10.3390/biom14030342.

Anti-PRL-3 Monoclonal Antibody inhibits the Growth and Metastasis of colorectal adenocarcinoma.

Sun S, Meng L, Xing X, Li N, Song Q, Qiao D J Cancer. 2023; 14(13):2585-2595.

PMID: 37670977 PMC: 10475362. DOI: 10.7150/jca.81702.

APPL1 Is a Prognostic Biomarker and Correlated with Treg Cell Infiltration via Oxygen-Consuming Metabolism in Renal Clear Cell Carcinoma.

Yang M, Gong C, Song K, Huang N, Chen H, Gong H Oxid Med Cell Longev. 2023; 2023:5885203.

PMID: 36846720 PMC: 9957629. DOI: 10.1155/2023/5885203.

TRPM4 and TRPV2 are two novel prognostic biomarkers and promising targeted therapy in UVM.

Wang J, Qiao S, Liang S, Qian C, Dong Y, Pei M Front Mol Biosci. 2022; 9:985434.

PMID: 36081847 PMC: 9445434. DOI: 10.3389/fmolb.2022.985434.

References

Ren T, Jiang B, Xing X, Dong B, Peng L, Meng L . Prognostic significance of phosphatase of regenerating liver-3 expression in ovarian cancer. Pathol Oncol Res. 2009; 15(4):555-60. DOI: 10.1007/s12253-009-9153-1. View

Xing X, Peng L, Qu L, Ren T, Dong B, Su X . Prognostic value of PRL-3 overexpression in early stages of colonic cancer. Histopathology. 2009; 54(3):309-18. DOI: 10.1111/j.1365-2559.2009.03226.x. View

Mizuno H, Kitada K, Nakai K, Sarai A . PrognoScan: a new database for meta-analysis of the prognostic value of genes. BMC Med Genomics. 2009; 2:18. PMC: 2689870. DOI: 10.1186/1755-8794-2-18. View

den Hollander P, Rawls K, Tsimelzon A, Shepherd J, Mazumdar A, Hill J . Phosphatase PTP4A3 Promotes Triple-Negative Breast Cancer Growth and Predicts Poor Patient Survival. Cancer Res. 2016; 76(7):1942-53. PMC: 4873402. DOI: 10.1158/0008-5472.CAN-14-0673. View

Gupta K, Miller J, Li J, Russell M, Charbonneau C . Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev. 2008; 34(3):193-205. DOI: 10.1016/j.ctrv.2007.12.001. View

Lai W, Liu L, Zeng Y, Wu H, Xu H, Chen S . KCNN4 channels participate in the EMT induced by PRL-3 in colorectal cancer. Med Oncol. 2013; 30(2):566. DOI: 10.1007/s12032-013-0566-z. View

Ghatalia P, Gordetsky J, Kuo F, Dulaimi E, Cai K, Devarajan K . Prognostic impact of immune gene expression signature and tumor infiltrating immune cells in localized clear cell renal cell carcinoma. J Immunother Cancer. 2019; 7(1):139. PMC: 6540413. DOI: 10.1186/s40425-019-0621-1. View

Zimmerman M, Homanics G, Lazo J . Targeted deletion of the metastasis-associated phosphatase Ptp4a3 (PRL-3) suppresses murine colon cancer. PLoS One. 2013; 8(3):e58300. PMC: 3610886. DOI: 10.1371/journal.pone.0058300. View

Sengal A, Velazquez J, Hahne M, Burke T, Abhyankar H, Reyes R . Overcoming T-cell exhaustion in LCH: PD-1 blockade and targeted MAPK inhibition are synergistic in a mouse model of LCH. Blood. 2020; 137(13):1777-1791. PMC: 8020265. DOI: 10.1182/blood.2020005867. View

10.

Xing X, Lian S, Hu Y, Li Z, Zhang L, Wen X . Phosphatase of regenerating liver-3 (PRL-3) is associated with metastasis and poor prognosis in gastric carcinoma. J Transl Med. 2013; 11:309. PMC: 3878674. DOI: 10.1186/1479-5876-11-309. View

11.

Lian S, Meng L, Yang Y, Ma T, Xing X, Feng Q . PRL-3 promotes telomere deprotection and chromosomal instability. Nucleic Acids Res. 2017; 45(11):6546-6571. PMC: 5499835. DOI: 10.1093/nar/gkx392. View

12.

Niu B, Zhou F, Su Y, Wang L, Xu Y, Yi Z . Different Expression Characteristics of LAG3 and PD-1 in Sepsis and Their Synergistic Effect on T Cell Exhaustion: A New Strategy for Immune Checkpoint Blockade. Front Immunol. 2019; 10:1888. PMC: 6693426. DOI: 10.3389/fimmu.2019.01888. View

13.

Chen F, Zhang Y, Senbabaoglu Y, Ciriello G, Yang L, Reznik E . Multilevel Genomics-Based Taxonomy of Renal Cell Carcinoma. Cell Rep. 2016; 14(10):2476-89. PMC: 4794376. DOI: 10.1016/j.celrep.2016.02.024. View

14.

Rios P, Li X, Kohn M . Molecular mechanisms of the PRL phosphatases. FEBS J. 2012; 280(2):505-24. DOI: 10.1111/j.1742-4658.2012.08565.x. View

15.

Lian S, Meng L, Liu C, Xing X, Song Q, Dong B . PRL-3 activates NF-κB signaling pathway by interacting with RAP1. Biochem Biophys Res Commun. 2012; 430(1):196-201. DOI: 10.1016/j.bbrc.2012.11.036. View

16.

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

17.

Gooden M, de Bock G, Leffers N, Daemen T, Nijman H . The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer. 2011; 105(1):93-103. PMC: 3137407. DOI: 10.1038/bjc.2011.189. View

18.

Johansson J, Marie K, Lu Y, Brombin A, Santoriello C, Zeng Z . PRL3-DDX21 Transcriptional Control of Endolysosomal Genes Restricts Melanocyte Stem Cell Differentiation. Dev Cell. 2020; 54(3):317-332.e9. PMC: 7435699. DOI: 10.1016/j.devcel.2020.06.013. View

19.

Li T, Fan J, Wang B, Traugh N, Chen Q, Liu J . TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017; 77(21):e108-e110. PMC: 6042652. DOI: 10.1158/0008-5472.CAN-17-0307. View

20.

Mizuuchi E, Semba S, Kodama Y, Yokozaki H . Down-modulation of keratin 8 phosphorylation levels by PRL-3 contributes to colorectal carcinoma progression. Int J Cancer. 2008; 124(8):1802-10. DOI: 10.1002/ijc.24111. View