POS-02.88: Gamma-delta T lymphocytes are of no prognostic value in clear cell renal cell carcinoma

Abstract Background: Little is known about the associations between PAK1 and anti-tumor immunity in clear-cell renal cell carcinoma (ccRCC). This study aims to explore the prognostic value of PAK1 in ccRCC patients and investigated the molecular immune mechanism for its oncogenic role. Methods: We retrospectively enrolled 282 ccRCC patients undergoing nephrectomy between 2005 and 2007 in Zhongshan hospital. Immunohistochemistry evaluated PAK1, CCL22, FOXP3 and CD8 expression in clinical specimens. Fresh tumor tissues, para-tumor tissues and peripheral blood samples for RT-PCR, ELISA, flow cytometry analyses were collected from patients who underwent nephrectomy in Zhongshan Hospital from September 2017 to April 2018. We compared clinical outcomes by Kaplan-Meier survival analysis and Cox regression model. Bioinformatics analysis performed in TCGA KIRC cohort. Results: High PAK1 expression indicated poorer overall survival (OS) and recurrence free survival (RFS) (both p<0.001) in ccRCC patients. Multivariate analyses indicated PAK1 as an independent prognostic factor. In clinical samples, PAK1 clearly correlated with immunosuppressive microenvironment in ccRCC tissues. Significantly, PAK1 positively correlated with Tumor-infiltrating regulatory T lymphocytes (Tregs). Furthermore, IL-10+ and TGF-β+ tumor-infiltrating Tregs both increased in PAK1 high tumors. Additionally, CCL22 was highly secreted in PAK1 high tumors. After treated by IPA-3 (an PAK1 inhibitor), CCL22 secretion was clearly inhibited (p<0.001). Finally, we built a nomogram to predict overall survival for ccRCC patients with higher predictive accuracy. Conclusions: Increased PAK1 expression predicted dismal prognosis in ccRCC patients by inducing tumor immune escape. IL-10+ and TGF-β+ tumor-infiltrating Tregs recruited by CCL22 play dominant immunosuppressive roles in PAK1 high tumors.

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N6‑methyladenosine RNA methylation regulators participate in malignant progression and have prognostic value in clear cell renal cell carcinoma

Oncology Reports ◽

10.3892/or.2020.7524 ◽

2020 ◽

Cited By ~ 1

Author(s):

Zongtai Zheng ◽

Shiyu Mao ◽

Yadong Guo ◽

Wentao Zhang ◽

Ji Liu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Value ◽

Clear Cell ◽

Malignant Progression ◽

Cell Renal Cell Carcinoma ◽

Rna Methylation

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Prognostic implications of Aquaporin 9 expression in clear cell renal cell carcinoma

Journal of Translational Medicine ◽

10.1186/s12967-019-2113-y ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 3

Author(s):

Wen-Hao Xu ◽

Shen-Nan Shi ◽

Yue Xu ◽

Jun Wang ◽

Hong-Kai Wang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Prognostic Value ◽

Clear Cell ◽

Roc Curves ◽

Functional Enrichment ◽

Clinicopathological Parameters ◽

Cell Renal Cell Carcinoma ◽

Aquaporin 9

Abstract Background Growing evidence has demonstrated immune reactivity as a confirmed important carcinogenesis and therapy efficacy for clear cell renal cell carcinoma (ccRCC). Aquaporin 9 (AQP9) is involved in many immune-related signals; however, its role in ccRCC remains to be elucidated. This study investigated AQP9 expression in tumor tissues and defined the prognostic value in ccRCC patients. Methods A total of 913 ccRCC patients with available RNA-sequence data from the Cancer Genome Atlas (TCGA) database and Fudan University Shanghai Cancer Center (FUSCC) were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained and validated using multiple datasets. A partial likelihood test from Cox regression analysis was developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method and log-rank test were performed to assess survival. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of AQP9 using area under the curve (AUC) score. Functional enrichment analyses and immune infiltration analysis were used to describe significantly involved hallmark pathways of hub genes. Results Significantly elevated transcriptional and proteomic AQP9 expressions were found in ccRCC samples. Increased AQP9 mRNA expression was significantly associated with advanced clinicopathological parameters and correlated with shorter PFS and OS in TCGA and FUSCC cohorts (p < 0.001). ROC curves suggested the significant diagnostic and prognostic ability of AQP9 (PFS, AUC = 0.823; OS, AUC = 0.828). Functional annotations indicated that AQP9 is involved in the most significant hallmarks including complement, coagulation, IL6/JAK–STAT3, inflammatory response and TNF-alpha signaling pathways. Conclusion Our study revealed that elevated AQP9 expression was significantly correlated with aggressive progression, poor survival and immune infiltrations in ccRCC patients, and we validated its prognostic value in a real-world cohort. These data suggest that AQP9 may act as an oncogene and a promising prognostic marker in ccRCC.

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