NOL-7 Serves As a Potential Prognostic-related biomarker for Hepatocellular Carcinoma

Overview

Journal Discov Oncol

Publisher Springer

Date 2025 Jan 21

PMID 39836310

Authors

Qiucheng Lei

Yingchun Huang

Feiwen Deng

Huazhen Zheng

Xitao Hong

Peng Wang

Jin Lv

Huanwei Chen

Zhenling Ji

Affiliations

Soon will be listed here.

Abstract

Background: Nucleolar protein 7 (NOL7), a specific protein found in the nucleolus, is crucial for maintaining cell division and proliferation. While the involvement of NOL7 in influencing the unfavorable prognosis of metastatic melanoma has been reported, its significance in predicting the prognosis of patients with Hepatocellular Carcinoma (HCC) remains unclear.

Methods: Aberrant expression of NOL7 in HCC and its prognostic value were evaluated using multiple databases, including TCGA, GTEx, Xiantao Academic, HCCDB, UALCAN, TISCH, and STRING. Immunohistochemistry (IHC) and quantitative real-time PCR were used to validate NOL7 expression levels in patients with HCC.

Results: NOL7 expression was higher in the HCC samples than in the normal samples (P < 0.05). NOL7 was strongly associated with elevated AFP levels, vascular invasion, TNM stage, poorer tumor differentiation, and poorer survival (all P < 0.05). Elevated NOL7 expression correlated with decreased overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) (all P < 0.05). Multivariate analysis revealed that NOL7 was an independent prognostic factor that was significantly related to OS and DSS. The nomogram showed a good predictive performance based on the calibration plot. In addition, NOL7 expression was significantly correlated with cell cycle modulators, immune checkpoints, and various immune cell populations. In addition, we identified eight potential pathways associated with NOL7 as the most promising pathways for NOL7 in HCC. Low-risk specimens were more sensitive to oxaliplatin, cisplatin, irinotecan, sorafenib, and cytarabine than high-risk specimens.

Conclusion: NOL7 may serve as a potential biomarker for predicting clinical outcomes and may provide guidance for clinical therapy in patients with HCC.

References

Kinor N, Shav-Tal Y . The dynamics of the alternatively spliced NOL7 gene products and role in nucleolar architecture. Nucleus. 2011; 2(3):229-45. PMC: 3149883. DOI: 10.4161/nucl.2.3.15893. View

Liu S, Tang Q, Huang J, Zhan M, Zhao W, Yang X . Prognostic analysis of tumor mutation burden and immune infiltration in hepatocellular carcinoma based on TCGA data. Aging (Albany NY). 2021; 13(8):11257-11280. PMC: 8109113. DOI: 10.18632/aging.202811. View

McCool M, Bryant C, Huang H, Ogawa L, Farley-Barnes K, Sondalle S . Human nucleolar protein 7 (NOL7) is required for early pre-rRNA accumulation and pre-18S rRNA processing. RNA Biol. 2023; 20(1):257-271. PMC: 10228412. DOI: 10.1080/15476286.2023.2217392. View

Kumar S, Pandey A . Potential Molecular Targeted Therapy for Unresectable Hepatocellular Carcinoma. Curr Oncol. 2023; 30(2):1363-1380. PMC: 9955633. DOI: 10.3390/curroncol30020105. View

Fancello L, Gandini S, Pelicci P, Mazzarella L . Tumor mutational burden quantification from targeted gene panels: major advancements and challenges. J Immunother Cancer. 2019; 7(1):183. PMC: 6631597. DOI: 10.1186/s40425-019-0647-4. View

Zhou S, Han Y, Yang R, Pi X, Li J . TIMM13 as a prognostic biomarker and associated with immune infiltration in skin cutaneous melanoma (SKCM). Front Surg. 2022; 9:990749. PMC: 9428353. DOI: 10.3389/fsurg.2022.990749. View

Sun D, Wang J, Han Y, Dong X, Ge J, Zheng R . TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment. Nucleic Acids Res. 2020; 49(D1):D1420-D1430. PMC: 7778907. DOI: 10.1093/nar/gkaa1020. View

Steven A, Seliger B . The Role of Immune Escape and Immune Cell Infiltration in Breast Cancer. Breast Care (Basel). 2018; 13(1):16-21. PMC: 6016054. DOI: 10.1159/000486585. View

Pang A, Ng I, Fan S, Kwong Y . Clinicopathologic significance of genetic alterations in hepatocellular carcinoma. Cancer Genet Cytogenet. 2003; 146(1):8-15. DOI: 10.1016/s0165-4608(03)00103-1. View

10.

Mankame T, Lingen M . The RB tumor suppressor positively regulates transcription of the anti-angiogenic protein NOL7. Neoplasia. 2013; 14(12):1213-22. PMC: 3540946. DOI: 10.1593/neo.121422. View

11.

Doci C, Zhou G, Lingen M . The novel tumor suppressor NOL7 post-transcriptionally regulates thrombospondin-1 expression. Oncogene. 2012; 32(37):4377-86. PMC: 6698137. DOI: 10.1038/onc.2012.464. View

12.

Zhou G, Doci C, Lingen M . Identification and functional analysis of NOL7 nuclear and nucleolar localization signals. BMC Cell Biol. 2010; 11:74. PMC: 2957388. DOI: 10.1186/1471-2121-11-74. View

13.

Ganesan P, Kulik L . Hepatocellular Carcinoma: New Developments. Clin Liver Dis. 2022; 27(1):85-102. DOI: 10.1016/j.cld.2022.08.004. View

14.

Doci C, Mankame T, Langerman A, Ostler K, Kanteti R, Best T . Characterization of NOL7 gene point mutations, promoter methylation, and protein expression in cervical cancer. Int J Gynecol Pathol. 2011; 31(1):15-24. PMC: 3237951. DOI: 10.1097/PGP.0b013e318220ba16. View

15.

Matthews H, Bertoli C, de Bruin R . Cell cycle control in cancer. Nat Rev Mol Cell Biol. 2021; 23(1):74-88. DOI: 10.1038/s41580-021-00404-3. View

16.

Dunn G, Dunn I, Curry W . Focus on TILs: Prognostic significance of tumor infiltrating lymphocytes in human glioma. Cancer Immun. 2007; 7:12. PMC: 2935751. View

17.

Kong F, Ye Q, Miao X, Liu X, Huang S, Xiong L . Current status of sorafenib nanoparticle delivery systems in the treatment of hepatocellular carcinoma. Theranostics. 2021; 11(11):5464-5490. PMC: 8039945. DOI: 10.7150/thno.54822. View

18.

Pelletier J, Thomas G, Volarevic S . Ribosome biogenesis in cancer: new players and therapeutic avenues. Nat Rev Cancer. 2017; 18(1):51-63. DOI: 10.1038/nrc.2017.104. View

19.

Santos G, Zielenska M, Prasad M, Squire J . Chromosome 6p amplification and cancer progression. J Clin Pathol. 2006; 60(1):1-7. PMC: 1860600. DOI: 10.1136/jcp.2005.034389. View

20.

Lian Q, Wang S, Zhang G, Wang D, Luo G, Tang J . HCCDB: A Database of Hepatocellular Carcinoma Expression Atlas. Genomics Proteomics Bioinformatics. 2018; 16(4):269-275. PMC: 6205074. DOI: 10.1016/j.gpb.2018.07.003. View