Apelin (APLN) is a biomarker contributing to the diagnosis and prognosis of hepatocellular carcinoma.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
03 09 2024
Historique:
received: 09 04 2024
accepted: 28 08 2024
medline: 4 9 2024
pubmed: 4 9 2024
entrez: 3 9 2024
Statut: epublish

Résumé

Liver cancer, classified as a malignant hepatic tumor, can be divided into two categories: primary, originating within the liver, and secondary, resulting from metastasis to the liver from other organs. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and the third leading cause of cancer-related deaths. The diagnosis and prognosis of HCC using current methods still face numerous challenges. This study aims to develop novel diagnostic and prognostic models while identifying new biomarkers for improved HCC treatment. Diagnostic and prognostic models for HCC were constructed using traditional binary classification methods and machine learning algorithms based on the TCGA database (Downloaded in August 2023). The mechanisms by which APLN (Apelin) affects HCC were investigated using single-cell sequencing data sourced from the GEO database (GSE149614). The diagnostic models yielded by various algorithms could effectively distinguished HCC samples from normal ones. The prognostic model, composed of four genes, was constructed using LASSO and Cox regression algorithms, demonstrating good performance in predicting the three-year survival rate of HCC patients. The HCC biomarker Apelin (APLN) was identified in this study. APLN in liver cancer tissues mainly comes from endothelial cells and is associated with the carcinogenesis of these cells. APLN expression is significantly upregulated in liver cancer tissues, marking it as a viable indicator of endothelial cell malignancy in HCC. Furthermore, APLN expression was determined to be an independent predictor of tumor endothelial cell carcinogenesis, unaffected by its modifications such as single nucleotide variation, copy number variation, and methylation. Additionally, liver cancers characterized by high APLN expression are likely to progress rapidly after T2 stage. Our study presents diagnostic and prognostic models for HCC with appreciably improved accuracy and reliability compared to previous reports. APLN is a reliable HCC biomarker and contributes to the establishment of our models.

Identifiants

pubmed: 39227683
doi: 10.1038/s41598-024-71495-z
pii: 10.1038/s41598-024-71495-z
doi:

Substances chimiques

Apelin 0
Biomarkers, Tumor 0
APLN protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

20441

Subventions

Organisme : National Key Research and Development Program of China
ID : 2018YFE0204503

Informations de copyright

© 2024. The Author(s).

Références

Vogel, A., Meyer, T., Sapisochin, G., Salem, R. & Saborowski, A. Hepatocellular carcinoma. The Lancet. 400, 1345–1362 (2022).
doi: 10.1016/S0140-6736(22)01200-4
Yang, J. D. et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat. Rev. Gastroenterol. Hepatol. 16, 589–604 (2019).
doi: 10.1038/s41575-019-0186-y pubmed: 31439937 pmcid: 6813818
Lurje, I. et al. Treatment strategies for hepatocellular carcinoma—a multidisciplinary approach. IJMS. 20, 1465 (2019).
doi: 10.3390/ijms20061465 pubmed: 30909504 pmcid: 6470895
Zhu, W.-W. et al. Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma. Clin. Cancer Res. 19, 3944–3954 (2013).
doi: 10.1158/1078-0432.CCR-12-3363 pubmed: 23719264 pmcid: 6314491
Gu, Y. et al. CCL14 is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma. Aging. 12, 784–807 (2020).
doi: 10.18632/aging.102656 pubmed: 31927532 pmcid: 6977663
Nakagawa, T. et al. Glycomic analysis of alpha-fetoprotein L3 in hepatoma cell lines and hepatocellular carcinoma patients. J. Proteome Res. 7, 2222–2233 (2008).
doi: 10.1021/pr700841q pubmed: 18479159
Yang, C. et al. Prognosis and personalized treatment prediction in TP53-mutant hepatocellular carcinoma: An in silico strategy towards precision oncology. Brief. Bioinform. 22, 164 (2021).
doi: 10.1093/bib/bbaa164
Wang, L., Liu, B.-X. & Long, H.-Y. Ablative strategies for recurrent hepatocellular carcinoma. World J. Hepatol. 15, 515–524 (2023).
doi: 10.4254/wjh.v15.i4.515 pubmed: 37206650 pmcid: 10190693
Liu, X.-N. et al. Multiple, “Omics” data-based biomarker screening for hepatocellular carcinoma diagnosis. WJG. 25, 4199–4212 (2019).
doi: 10.3748/wjg.v25.i30.4199 pubmed: 31435173 pmcid: 6700689
Saxena, N. K. et al. Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Res. 67, 2497–2507 (2007).
doi: 10.1158/0008-5472.CAN-06-3075 pubmed: 17363567 pmcid: 2925446
Chen, H. et al. APLN promotes hepatocellular carcinoma through activating PI3K/Akt pathway and is a druggable target. Theranostics. 9, 5246–5260 (2019).
doi: 10.7150/thno.34713 pubmed: 31410213 pmcid: 6691573
Kanehisa, M. KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 28, 27–30 (2000).
doi: 10.1093/nar/28.1.27 pubmed: 10592173 pmcid: 102409
Kanehisa, M. Toward understanding the origin and evolution of cellular organisms. Protein Sci. 28, 1947–1951 (2019).
doi: 10.1002/pro.3715 pubmed: 31441146 pmcid: 6798127
Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 51, D587–D592 (2023).
doi: 10.1093/nar/gkac963 pubmed: 36300620
Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J. Clin. 71, 209–249 (2021).
doi: 10.3322/caac.21660
Fu, J. & Wang, H. Precision diagnosis and treatment of liver cancer in China. Cancer Lett. 412, 283–288 (2018).
doi: 10.1016/j.canlet.2017.10.008 pubmed: 29050983
Zeng, H. et al. Cancer survival in China, 2003–2005: A population-based study. Int. J. Cancer. 136, 1921–1930 (2015).
doi: 10.1002/ijc.29227 pubmed: 25242378
Tang, B. et al. Diagnosis and prognosis models for hepatocellular carcinoma patient’s management based on tumor mutation burden. J. Adv. Res. 33, 153–165 (2021).
doi: 10.1016/j.jare.2021.01.018 pubmed: 34603786 pmcid: 8463909
Long, J. et al. DNA methylation-driven genes for constructing diagnostic, prognostic, and recurrence models for hepatocellular carcinoma. Theranostics. 9, 7251–7267 (2019).
doi: 10.7150/thno.31155 pubmed: 31695766 pmcid: 6831284
Cheng, B., Zhou, P. & Chen, Y. Machine-learning algorithms based on personalized pathways for a novel predictive model for the diagnosis of hepatocellular carcinoma. BMC Bioinformatics. 23, 248 (2022).
doi: 10.1186/s12859-022-04805-9 pubmed: 35739471 pmcid: 9219178
Tellapuri, S., Sutphin, P. D., Beg, M. S., Singal, A. G. & Kalva, S. P. Staging systems of hepatocellular carcinoma: A review. Indian J. Gastroenterol. 37, 481–491 (2018).
doi: 10.1007/s12664-018-0915-0 pubmed: 30593649
Liu, G.-M., Zeng, H.-D., Zhang, C.-Y. & Xu, J.-W. Identification of a six-gene signature predicting overall survival for hepatocellular carcinoma. Cancer Cell Int. 19, 138 (2019).
doi: 10.1186/s12935-019-0858-2 pubmed: 31139015 pmcid: 6528264
Chen, W., Ou, M., Tang, D., Dai, Y. & Du, W. Identification and validation of immune-related gene prognostic signature for hepatocellular carcinoma. J. Immunol. Res. 2020, 1–14 (2020).
Tang, Y. et al. Identification and validation of a prognostic model based on three MVI-related genes in hepatocellular carcinoma. Int. J. Biol. Sci. 18, 261–275 (2022).
doi: 10.7150/ijbs.66536 pubmed: 34975331 pmcid: 8692135
Villanueva, A. Hepatocellular carcinoma. N. Engl. J. Med. 380, 1450–1462 (2019).
doi: 10.1056/NEJMra1713263 pubmed: 30970190
Muto, J. et al. The apelin-APJ system induces tumor arteriogenesis in hepatocellular carcinoma. Anticancer Res. 34, 5313–5320 (2014).
pubmed: 25275024
Hall, C. et al. Inhibition of the apelin/apelin receptor axis decreases cholangiocarcinoma growth. Cancer Lett. 386, 179–188 (2017).
doi: 10.1016/j.canlet.2016.11.025 pubmed: 27894959
Wan, Y. et al. Dysregulated microRNA-224/apelin axis associated with aggressive progression and poor prognosis in patients with prostate cancer. Hum. Pathol. 46, 295–303 (2015).
doi: 10.1016/j.humpath.2014.10.027 pubmed: 25532941
Hoffmann, M., Fiedor, E. & Ptak, A. Bisphenol A and its derivatives tetrabromobisphenol A and tetrachlorobisphenol A induce apelin expression and secretion in ovarian cancer cells through a peroxisome proliferator-activated receptor gamma-dependent mechanism. Toxicol. Lett. 269, 15–22 (2017).
doi: 10.1016/j.toxlet.2017.01.006 pubmed: 28111160
Harford-Wright, E. et al. Pharmacological targeting of apelin impairs glioblastoma growth. Brain. 140, 2939–2954 (2017).
doi: 10.1093/brain/awx253 pubmed: 29053791 pmcid: 5841205

Auteurs

Xi Mao (X)

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China.

Xiaoya Zhu (X)

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.

Tong Pan (T)

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.

Zehui Liu (Z)

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.

Pingping Shangguan (P)

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.

Yi Zhang (Y)

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.

Yingle Liu (Y)

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China. mvlwu@whu.edu.cn.
Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, China. mvlwu@whu.edu.cn.

Xiwen Jiang (X)

School of Life Sciences and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou, China. yuanyecat@vip.sina.com.

Qi Zhang (Q)

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China. gracetey@whu.edu.cn.

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