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

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 (P=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+ (P =0.037)/CD8+ (P =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.

SUBMITTER: Song Q

PROVIDER: S-EPMC8495008 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What's more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.

Project description:BackgroundIncreased evidence has indicated that the tumour microenvironment plays an essential in the development, treatment and prognosis of head and neck squamous cell carcinoma (HNSC). Recent studies have indicated CC chemokine receptor 4 (CCR4) plays an essential role in tumor invasion and other adverse biological behavior. This study used data from the Cancer Genome Atlas (TCGA) database to explore the role of CCR4 in HNSC and its clinical significance.MethodsThe gene expression and clinical data of HNSC patients in the TCGA database were extracted. Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the expression of CCR4 in tumor and non-tumor tissue. Kaplan-Meier survival analysis was used to analyze the relationship between CCR4 expression and overall survival rate (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HNSC. A logistic regression model was used to analyze the relationships between various clinical factors and CCR4 expression. Gene Set Enrichment Analysis (GSEA) was used to explore the potential role of CCR4 in HNSC. Additionally, we explored the relationship between CCR4 and immune infiltration.ResultsThe expression of CCR4 in HNSC was not significantly different from that in normal tissue. The expression level of CCR4 in wild-type TP53 was higher than that in mutant TP53. Cox regression analysis showed the expression level of CCR4 was related to the patient's tumor grade and Tumor-Node-Metastasis (TNM) stage. CCR4 expression level is an independent prognostic factor. CCR4 is positively correlated with immune infiltration and immune checkpoints expression levels. The results of GSEA revealed that the high CCR4 expression group genes were enriched in allograft rejection, inflammatory response, IL-6/JAK/STAT3 signaling, interferon gamma response, and KRAS signaling up. Low CCR4 expression group genes were enriched in oxidative phosphorylation, MYC targets v1, DNA repair, reactive oxygen species pathway, and P53 pathway. Further, our study indicated CCR4 can also predict the prognosis of radiotherapy patients.ConclusionsOur study found that CCR4 was a prognostic marker related to HNSC immune infiltration, and patients with high expression of CCR4 had a better prognosis.

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

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