Identification of LIMK1 as a biomarker in clear cell renal cell carcinoma: from data mining to validation

从数据挖掘到验证,鉴定 LIMK1 作为透明细胞肾细胞癌的生物标志物

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Abstract

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is one of the most common types of renal cancer. LIM kinase 1 (LIMK1) reportedly plays an important role in tumorigenesis. However, the involvement of LIMK1 in the progression of ccRCC remains ambiguous. METHODS: Based on the TCGA and CPTAC databases, the expression of LIMK1 in ccRCC was evaluated. In the TCGA-ccRCC cohort, the relationships between LIMK1 and immune cell infiltration as well as immune checkpoints were assessed. The high expression of LIMK1 in ccRCC was verified by qRT-PCR in four RCC cell lines. Immunohistochemistry was used to evaluate the expression of LIMK1 in clinical samples. The association between LIMK1 expression and survival prognosis was explored via Kaplan-Meier survival curve in the TCGA-ccRCC and local cohorts. The effects of LIMK1 knockdown on the proliferation, migration, and invasion abilities of RCC cells were evaluated via colony, CCK-8, wound healing, and Transwell assays. RESULTS: Elevated expression level of LIMK1 was found in the TCGA-ccRCC cohort and was confirmed in RCC cell lines and clinical samples. Up-regulation of LIMK1 was found to be correlated with poor prognosis in TCGA-ccRCC and external cohorts. In addition, high-LIMK1 was associated with clinicopathological stage, immune cell infiltration and immune checkpoint in ccRCC. Importantly, knockdown of LIMK1 diminished the capability of proliferation, migration, and invasion in RCC cells. CONCLUSION: LIMK1 may serve as a promising diagnostic and prognostic biomarker of ccRCC.

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