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Multi-omics Analysis Revealed the Novel Role of NQO1 in Microenvironment, Prognosis and Immunotherapy of Hepatocellular Carcinoma

Overview
Journal Sci Rep
Specialty Science
Date 2025 Mar 13
PMID 40074806
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Abstract

NAD(P)H dehydrogenase quinone 1 (NQO1) is overexpressed in various cancers and is strongly associated with an immunosuppressive microenvironment and poor prognosis. In this study, we explored the role of NQO1 in the microenvironment, prognosis and immunotherapy of Hepatocellular carcinoma (HCC) using multi-omics analysis and machine learning. The results revealed that NQO1 was significantly overexpressed in HCC cells. NQO1HCC cells were correlated with poor prognosis and facilitated tumor-associated macrophages (TAMs) polarization to M2 macrophages. We identified core NQO1-related genes (NRGs) and developed the NRGs-related risk-scores in hepatocellular carcinoma (NRSHC). The comprehensive nomogram integrating NRSHC, age, and pathological tumor-node-metastasis (pTNM) Stage achieved an area under the curve (AUC) above 0.7, demonstrating its accuracy in predicting survival outcomes and immunotherapy responses of HCC patients. High-risk patients exhibited worse prognoses but greater sensitivity to immunotherapy. Additionally, a web-based prediction tool was designed to enhance clinical utility. In conclusion, NQO1 may play a critical role in M2 polarization and accelerates HCC progression. The NRSHC model and accompanying tools offer valuable insights for personalized HCC treatment.

References
1.
Zhu H, Li H, Huang M, Yang W, Yin G, Zhong B . Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001). Signal Transduct Target Ther. 2023; 8(1):58. PMC: 9905571. DOI: 10.1038/s41392-022-01235-0. View

2.
Yang X, Yang C, Zhang S, Geng H, Zhu A, Bernards R . Precision treatment in advanced hepatocellular carcinoma. Cancer Cell. 2024; 42(2):180-197. DOI: 10.1016/j.ccell.2024.01.007. View

3.
Jaiswal A, BELL D, Radjendirane V, Testa J . Localization of human NQO1 gene to chromosome 16q22 and NQO2-6p25 and associated polymorphisms. Pharmacogenetics. 1999; 9(3):413-8. DOI: 10.1097/00008571-199906000-00020. View

4.
Blanche P, Dartigues J, Jacqmin-Gadda H . Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks. Stat Med. 2013; 32(30):5381-97. DOI: 10.1002/sim.5958. View

5.
Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View