Identifying the Role of NUDCD1 in Human Tumors from Clinical and Molecular Mechanisms: A Study Based On Comprehensive Bioinformatics and Experimental Validation

Abstract

Abstract Purpose Cancer is a major public health condition characterized by high morbidity and mortality. NUDCD1 (NudC domain-containing 1) is abnormally activated in multiple tumors and has been identified as a cancer antigen. But there is still no pan-cancer analysis available for NUDCD1 in human cancers. Methods The role of NUDCD1 across multiple tumors was explored using data from the public databases including HPA, TCGA, GEO, GTEx, TIMER2, TISIDB, UALCAN, GEPIA2, cBioPortal, GSCA and so on. Molecular experiments (e.g., quantitative real-time PCR, immunohistochemistry and western blot) were conducted to validate the expression and biological function of NUDCD1 in STAD tissues and cells. Results NUDCD1 was highly expressed in most tumors and its levels were associated with the prognosis of cancer patients. Multiple genetic and epigenetic features of NUDCD1 exist in different cancers such as uterine corpus endometrial carcinoma or kidney renal papillary cell carcinoma. NUDCD1 was associated with expression levels of recognized immune checkpoints (anti-CTLA-4) and immune infiltrates (e.g., CD4 + and CD8 + T cells) in some cancers. Moreover, NUDCD1 correlated with the CTRP and GDSC drug sensitivity and acted as a link between chemicals and cancers. The functional mechanisms of NUDCD1 included RNA metabolism- and protein processing-associated functions. Importantly, NUDCD1-related genes were enriched in several tumors (e.g., COAD, STAD and ESCA) and affected apoptosis, cell cycle and DNA damage cancer-related pathways. Furthermore, expression, mutation and copy number variations for the gene sets were also associated with prognosis. At last, we experimentally validated the overexpression of NUDCD1 in STAD clinical samples and determined its contribution to STAD in vitro and in vivo. Conclusions NUDCD1 was involved in diverse biological processes and it influenced the occurrence and development of cancers through diverse underlying mechanism. This first pan-cancer analysis for NUDCD1 provides a comprehensive understanding about its roles across various cancer types, especially in STAD.