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High CLEC-2 expression associates with unfavorable postoperative prognosis of patients with clear cell renal cell carcinoma.

ABSTRACT: We enrolled a total of 277 patients who received nephrectomy due to clear cell renal cell carcinoma (ccRCC) in Zhongshan Hospital from Jan 2005 to Jun 2007. Immunohistochemistry was performed to evaluate the impact of CLEC-2 positive cell infiltration on the overall survival (OS) and recurrence-free survival (RFS) of patients with ccRCC. Kaplan-Meier analysis showed that high CLEC-2 positive cell infiltration in tumor tissue indicated poorer OS and RFS (OS, p < 0.001; RFS, p = 0.002). High CLEC-2 positive cell infiltration is also an independent risk factor for OS and RFS in multivariate analyses (OS, p = 0.004; RFS, p = 0.009). CLEC-2 positive cell infiltration could also stratify ccRCC patients' survival with University of California Integrated Staging System (UISS) stratum in the mediate-risk and high-risk groups. We constructed two nomograms incorporating parameters derived from multivariate analyses to predict patients' OS and RFS (OS, c-index 0.813; RFS, c-index 0.716). In conclusion, high CLEC-2 positive cell infiltration in ccRCC is an independent adverse prognostic factor for patients, and established nomograms based on this information could help predict ccRCC patients' OS and RFS.

SUBMITTER: Xiong Y

PROVIDER: S-EPMC5325393 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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High CLEC-2 expression associates with unfavorable postoperative prognosis of patients with clear cell renal cell carcinoma.

Xiong Ying Y Liu Li L Xia Yu Y Wang Jiajun J Xi Wei W Bai Qi Q Qu Yang Y Long Qilai Q Xu Jiejie J Guo Jianming J

Oncotarget 20160901 39

We enrolled a total of 277 patients who received nephrectomy due to clear cell renal cell carcinoma (ccRCC) in Zhongshan Hospital from Jan 2005 to Jun 2007. Immunohistochemistry was performed to evaluate the impact of CLEC-2 positive cell infiltration on the overall survival (OS) and recurrence-free survival (RFS) of patients with ccRCC. Kaplan-Meier analysis showed that high CLEC-2 positive cell infiltration in tumor tissue indicated poorer OS and RFS (OS, p < 0.001; RFS, p = 0.002). High CLEC- ...[more]

PMID: 27564117

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Project description:BackgroundKidney renal clear cell carcinoma (KIRC) is the most common pathological subtype of renal cell cancer. APOBEC3 activity has been identified in a variety of human cancers. Although its involvement in cancer has been studied widely, its influence on the tumor immune microenvironment remains poorly understood. Therefore, this study aimed to focus on the effect of APOBEC3 on tumor immune microenvironment of KIRC.MethodsIn this study, we comprehensively analyzed the expression and prognostic significance of the APOBEC3 family in pan-cancer using multiple databases. The functions of key APOBEC3 family members were further investigated in KIRC, with APOBEC3G determined to be a candidate biomarker for unfavorable prognosis. We subsequently explored the correlation of APOBEC3G with the tumor immune environment in KIRC by analyzing the Cancer Genome Atlas (TCGA) dataset, then validated the prognostic significance and PD-L1 correlation of APOBEC3G by using tissue microarrays which included 233 primary tumor samples from patients with renal clear cell carcinoma.ResultsThe APOBEC3 family was overexpressed in KIRC and high APOBEC3 expression predicted poor prognosis. In addition, APOBEC3G was positively correlated with the expression of immunoinhibitors such as TIGIT, LAG3, CD96, PD-1, and CTLA4. In addition, APOBEC3G had a positive correlation with immunosuppressive cells, including regulatory T cell and myeloid-derived suppressor cell. Finally, based on 233 clinical samples, we validated that high expression of APOBEC3G contributed to a poor prognosis for KIRC patients and the positive relationship between APOBEC3G and PD-L1 expression. High APOBEC3G expression was also found to be more common in patients with sarcomatoid histology (P = 0.0026).ConclusionsOur study showed that APOBEC3G was a prognostic biomarker correlated with the immune response in KIRC. In addition, APOBE3G had a positive correlation with PD-L1 expression and sarcomatoid histology, perhaps suggesting the potential impact of APOBEC3G on immunotherapy.

Project description:BackgroundCDC6 (Cell division control protein 6), located at chromosome 17q21.3, plays an important role in the early stage of DNA replication and has unique functions in various malignant tumors. Here, we evaluate the relationship between CDC6 expression and oncology outcomes in patients with clear cell renal cell carcinoma (ccRCC).MethodsA retrospective analysis of 118 ccRCC patients in Affiliated Hospital of Nantong University from 2015 to 2017 was performed. Triplicate tissue microarrays (TMA) were prepared from formalin-fixed and paraffin-embedded specimens. Immunohistochemistry (IHC) was conducted to evaluate the relationship between CDC6 expression and standard pathological features and prognosis. The RNA sequencing data and corresponding clinical information were acquired from the TCGA database. GSEA was used to identify signal pathways related to CDC6. Cox regression analysis was used to assess independent prognostic factors. In addition, the relationship between CDC6 and immunity was also investigated.ResultsThe results of Kaplan-Meier curve indicated that the OS of the patients with high expression of CDC6 was shorter than that of the patients with low CDC6 expression. Integrating the TCGA database and IHC staining, the results showed that CDC6 in ccRCC tissue was obviously up-regulated compared with adjacent normal kidney tissue. The results of Logistic regression analysis demonstrated that ccRCC patients with high expression of CDC6 are more likely to develop advanced disease than ccRCC patients with low CDC6 expression. The results of GSEA showed that the high expression of CDC6 was related to multiple signaling pathways. As for immunity, it was also related to TMB, immune checkpoint molecules, tumor microenvironment and immune infiltration. There were significantly correlations with CDC6 and immune cell infiltration levels and tumor microenvironment. The results of further results of the TCGA database showed that CDC6 was obviously related to immune checkpoint molecules and immune cells.ConclusionsIncreased expression of CDC6 is a potentially prognostic factor of poor prognosis in ccRCC patients.

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High CLEC-2 expression associates with unfavorable postoperative prognosis of patients with clear cell renal cell carcinoma.

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High CLEC-2 expression associates with unfavorable postoperative prognosis of patients with clear cell renal cell carcinoma.

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