Disulfidptosis-related NCK associated protein 1 as a potential biomarker for multiple tumor types: A pan-cancer analysis based on public databases

Abstract

In the past decade, a number of cancer types have been reported to be associated with NCKAP1 encoded as a component of the WASF regulatory complex (WRC) and a poor prognosis. A study of the role of NCKAP1 across various types of tumors was conducted using data from The Cancer Genome Atlas (TCGA). There was an alteration in NCKAP1 expression in most tumor types when compared to corresponding non-tumor tissues. Survival analysis revealed that NCKAP1 overexpression was associated with poor OS and DFS only in kidney renal clear cell carcinoma (KIRC), and upregulated NCKAP1 expression was also significantly associated with the advanced cancer stage suggesting malignant progression in KIRC based on TCGA datasets using GEPIA2; Meanwhile, IHC staining showed NCKAP1 levels of KIRC tissues were significantly lower than normal tissues from HPA database. Following that, NCKAP1 alteration was associated with poor prognosis in cervical squamous cell carcinoma (CSCC) and lung adenocarcinoma (LUAD) patients in terms of PFS analyzed by cBioPortal. As a result, a positive correlation was observed between NCKAP1 expression and cancer-associated fibroblast infiltration in ACC, BRCA, CESC, LGG, and STAD. According to Gene Ontology analysis, NCKAP1 encodes a gene that regulates the actin cytoskeleton function. It was demonstrated from the protein interaction network that NCKAP1 interacts physically with CYFIP1, ABI2, WASF2 and BRK1, which have been well-characterized as actin cytoskeleton cycle regulators and cell disulfidptosis. There was a significant correlation between NCKAP1 expression and tumor prognosis in this multi-tumor study.