Pan-cancer analysis portrays NVL2 as a novel diagnostic and prognostic biomarker

Abstract

Nuclear VCP Like 2 or NVL2, an ATPases Associated with diverse cellular Activities (AAA+) family protein, has recently been linked with various cancers. By systematic bioinformatics analyses, here we predict the prospect of NVL2 as a cancer biomarker. Our pan-cancer analyses reveal that NVL2 is overexpressed in cancers [GEPIA2, OncoDB, and UALCAN (TCGA) databases] and the top five cancers with elevated expression (more than two fold) of NVL2 are Breast Invasive Carcinoma, Testicular Germ Cell Tumors, Cholangiocarcinoma, Diffuse large B cell lymphoma, and Thymoma. NVL2 is also highly expressed in all stages of most cancers. Additionally, this high expression was found to be associated with the reduced survival rate of cancer patients (Kaplan-Meier Plotter, GEPIA2, and OncoDB databases). Since genetic alteration is one of the major causes of cancer, we investigated the mutation and copy number amplification status (cBioPortal and COSMIC databases) of NVL2 across the cancers. Many potential mutation sites were predicted (cBioPortal and COSMIC databases) and most strikingly, a total of fourteen mutation sites were observed at the ATPase domain of NVL2. This signifies that these are the mutations that might have a role in carcinogenesis. The copy number amplification study also revealed the high amplification percentage of NVL2 across different cancers. We further focused on the functional characteristics of the protein NVL2 across the cancers. The protein-protein interaction analyses found the proteins like SKIV2L2, WDR12, WDR74, UTP18, NAT10, TERT, DKC1, GTPBP4, BOP1, TEP1 directly interact with NVL2. The top canonical pathways indicated that NVL2 has crucial functions in oncogenesis (DAVID). We, therefore, surmise that NVL2 could be considered as a potential prognostic and diagnostic biomarker and a promising target for multiple cancers.