Identification of NK cell inhibitory ligand CLEC2D-associating immune infiltration landscape and prognostic value in kidney renal clear cell carcinoma

Abstract

Abstract Background Kidney renal clear cell carcinoma (KIRC), the most common pathological subtype of RCC, is a characteristics of heterogeneous diseases, and the outcome was dismay with immense diversity. KIRC is obviously resistant to radiotherapy and chemotherapy. In addition, increasing evidence has demonstrated that C-type lectin-like domain family 2 (CLEC2D) expression in cancer contributes to immune escape and thereby emerges as a target for natural killer (NK) cell-mediated immunotherapy. Therefore, we aimed to identify and validate the specific and detailed effect and mechanism of CLEC2D in KIRC. Methods CLEC2D expression in KIRC and normal tissues from TCGA were preliminatively screened, and further confirmed in a separate cohort of the GEO. Multivariate analysis and Kaplan-Meier (KM) curves were used to evaluate the relationship between CLEC2D expression and clinicopathologic parameters, and overall survival (OS). Subsequently, noncoding RNAs (ncRNAs) responsible for CLEC2D over-expression were identified by a combination of a series of expression, correlation, and survival analyses. Moreover, we further studied the relationship between CLEC2D expression and immune cell. The compounds were collected from the CellMiner database to examine the significance of CLEC2D in predicting chemotherapy sensitivity. Results Contrast to normal tissues, CLEC2D level was significantly higher in KIRC (p < 0.05). Elevated CLEC2D level was tightly correlated with higher grade malignancy and M, N, and tumor stage. Furthermore, univariate and multivariate analyses demonstrated that KIRC cases with high CLEC2D level had shorter OS time than patients with low CLEC2D level (p < 0.05). Subsequently, the LINC00894/-miR-30c-2-3p axis may be considered as the most latent upstream ncRNA-related pathway for CLEC2D in KIRC. Moreover, CLEC2D expression was markedly positively associated with tumor infiltrating immune cells (TIICs), markers of immune cells, and IC. In addition, our research indicated that several drugs IC50s closely related to CLEC2D expression were screened. Conclusions In conclusion, abundant expression of CLEC2D was correlated with disease progression and reduced prognosis, and there is sufficient TIICs in KIRC, suggesting that CLEC2D may serve as a promising prognostic biomarker and provide a novel target for tumor immunotherapy of KIRC.