Elevated NDC1 expression predicts poor prognosis and correlates with immunity in hepatocellular carcinoma

Abstract

Background: NDC1 was identified to be a tumor-promoting factor in non-small cell lung cancer and cervical cancer. However, no report had clarified the relationship between NDC1 and hepatocellular carcinoma (HCC). In this paper, we explored the expression and potential functions of NDC1 in HCC for the first time through the rational application of bioinformatics and relevant basic experiments.Methods: NDC1-related expression profiles and clinical data of HCC patients were collected from The Cancer Genome Atlas (TCGA) database, which were verified via quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Univariate and multivariate Cox regression analyses were used to identify NDC1 as an independent factor for HCC prognosis, and NDC1-related signaling pathways were determined by gene set enrichment analysis (GSEA). Furthermore, we deeply probed the potential links of NDC1 to immunity and immune response. Finally, the bioeffects and underlying mechanisms of ectopic NDC1 overexpression and depletion were determined in HepG2 cells by immunoblotting, flow cytometry, Cell-Counting-Kit-8 (CCK-8), and EDU (5-Ethynyl-2'-deoxyuridine).Results: Up-regulated expression of NDC1 was detected by means of the TCGA database, which was consistent with the results obtained from further qRT-PCR, immunohistochemistry and the CPTAC database. Kaplan-Meier (K-M) survival analysis revealed a worse prognosis in HCC patients with high NDC1 expression. Besides, NDC1 was certified to be closely linked to tumor histologic grade, clinical stage and T stage. Moreover, univariate and multivariate Cox regression analyses defined NDC1 as an independent element for HCC prognosis. NDC1-related signaling pathways, utilizing GSEA analysis, were subsequently found out. What's more, NDC1 expression was detected to be enormously associated with microsatellite instability (MSI), immune cell infiltration, immune checkpoint molecules and immune cell pathways. As for immunotherapy, we discovered that different risk groups tended to have different immune checkpoint inhibitor responses, which indicated crucial implication value of NDC1 for HCC immunotherapy. More interestingly, we observed that the overexpression of NDC1 could promote the migration and invasion of HCC cells.Conclusions: Our article demonstrated that NDC1 might serve as a valuable predictor in the prognosis and immunotherapy of HCC. NDC1 played an oncogenic role in HCC.

NDC1 promotes hepatocellular carcinoma tumorigenesis by targeting BCAP31 to activate PI3K/AKT signaling

“…Therefore, this research aims to investigate the involvement of NDC1 in the progression of HCC. The varying impact of NDC1 in different cancer types, such as colon cancer and HCC, [15,18] suggests an organ-specific role in the development of malignancy. Urgent advances are needed to unravel the underlying mechanisms of NDC1 in carcinogenesis to address this lethal disease.…”

Pan-cancer analysis and experimental validation identify ndc1 as a potential immunological, prognostic and therapeutic biomarker in pancreatic cancer

“…At present, studies on NDC1 mainly are involved in lung cancer, colon cancer, cervical cancer, esophageal cancer and hepatocellular carcinoma [ 8 – 13 ], and there was no previous report in pancreatic cancers. The latest research revealed that pancreatic cancer is a highly malignant cancer and the 5-year survival rate is reported to 3% only [ 23 ].…”

“…Jiang XY et al [ 12 ] uncovered that NDC1 could advance the initiation and progression of cervical cancer via the Wnt/β-catenin pathway. Qing L et al [ 13 ] showed that NDC1 is a prognostic and immunotherapy predictor of hepatocellular carcinoma and that overexpression of NDC1 can promote the migration and invasion of hepatocellular carcinoma. In the field of oncology, NDC1 has shown its potential as a prognostic marker for multiple tumors.…”