Abstract
BackgroundKidney Renal Clear Cell Carcinoma (KIRC) is one of the most prevalent types of cancer worldwide. KIRC has a poor prognosis and, to date, immunotherapy based on immune checkpoints is the most promising treatment. However, the role of immune checkpoints in KIRC remains ambiguous.MethodsBioinformatics analyses and qRT-PCR were performed to explore and further confirm the prognostic value of immune checkpoint genes and their correlation with immune infiltration in KIRC samples.ResultsThe expression of the immune checkpoint genes CD274, PDCD1LG2, HAVCR2, CTLA4, TIGFT, LAG3, and PDCD1 was upregulated in KIRC tissues. These genes were involved in the activation of the apoptosis pathway in KIRC. Low expression of CD274 and HAVCR2 and high expression of CTLA4 were associated with poor overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of KIRC patients. The univariate and multivariate analyses revealed that CTLA4, HAVCR2, age, pTNM stage, and tumor grade were independent factors affecting the prognosis of KIRC patients. A predictive nomogram demonstrated that the calibration plots for the 3‐year and 5‐year OS probabilities showed good agreement compared to the actual OS of KIRC patients. The expression of CTLA4 and HAVCR2 were positively associated with immune cell infiltration, immune biomarkers, chemokines, and chemokine receptors. Moreover, miR-20b-5p was identified as a potential miRNA target of CTLA4 in KIRC.ConclusionOur study clarified the prognostic value of several immune checkpoint regulators in KIRC, revealing a CTLA4/miR-20b-5p axis in the control of immune cell infiltration in the tumor microenvironment.
Highlights
Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors worldwide, accounting for 2.4% of all cancers [1]
According to the data from the Cancer Genome Atlas (TCGA), the mRNA expression of several immune checkpoint molecules revealed that the expression of CD274 (p = 1.18e-05), CTLA4 (p = 4.77e-28), HAVCR2 (p = 3.18e-20), LAG3 (p =1.04e-29), PDCD1LG2 (p = 2.39e-13), PDCD1 (p = 1.44e-27), and TIGFT (p = 3.4e-29) were upregulated in Kidney Renal Clear Cell Carcinoma (KIRC) tissues compared with normal tissues (Figure 1)
The expression of HAVCR2, CTLA4, and TIGIT was upregulated in KIRC tissues compared with normal tissues with a fold change of 3.536, 11.413, and 7.749, respectively [17] (Supplementary Table 2 and Supplementary Figure 1, p < 0.05)
Summary
Renal cell carcinoma (RCC) is one of the most prevalent malignant tumors worldwide, accounting for 2.4% of all cancers [1]. Over 403,000 people are initially diagnosed with RCC every year, and 175,000 patients will die of this disease [2]. Clear cell renal cell carcinoma (KIRC or ccRCC) is the most frequent histological subtype of RCC, and it accounts for most cancer-related deaths [3, 4]. Due to the lack of significant clinical symptomatology, KIRC can remain clinically occult, and patients are initially diagnosed in an advanced TNM stage. Late diagnosis generally correlates with lower survival, leading to a poor 5-years survival rate in KIRC patients [5]. Kidney Renal Clear Cell Carcinoma (KIRC) is one of the most prevalent types of cancer worldwide. The role of immune checkpoints in KIRC remains ambiguous
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