Dynamic network biomarker C1QTNF1 regulates tumor formation at the tipping point of hepatocellular carcinoma

Authors

  • Haoyuan Yu Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China https://orcid.org/0000-0002-5567-8885
  • Xijing Yan Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
  • Guanxing Chen Artificial Intelligence Medical Research Center, School of Intelligent Systems Engineering, Sun Yat-sen University, Shenzhen, China
  • Rong Li Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
  • Zhou Yang Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
  • Zhixing Liang Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
  • Linsen Ye Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China
  • Yunhao Chen Biotherapy Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
  • Yang Li Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China

DOI:

https://doi.org/10.17305/bb.2024.10103

Keywords:

Hepatocellular carcinoma (HCC), Dynamic Network Biomarker (DNB), C1q and tumor necrosis factor (TNF) related 1 (C1QTNF1), diagnosis, prognosis

Abstract

Identifying the precise moment before the onset of hepatocellular carcinoma (HCC) remains a significant challenge in the medical field. The existing biomarkers fall short of pinpointing the critical point preceding HCC formation. This study aimed to determine the exact tipping point for the transition from cirrhosis to HCC, identify the core Dynamic Network Biomarker (DNB), and elucidate its regulatory effects on HCC. A spontaneous HCC mouse model was established to mimic HCC formation in patients with chronic hepatitis. Using the DNB method, C1q and tumor necrosis factor (TNF) related 1 (C1QTNF1) protein was identified as the key DNB at the crucial tipping time of spontaneous HCC development. Both in vitro and in vivo studies showed that C1QTNF1 could inhibit tumor growth. Overexpression of C1QTNF1 before the tipping point effectively prevented HCC occurrence. Patients with elevated C1QTNF1 expression demonstrated improved overall survival (OS) (P = 0.03) and disease-free survival (DFS) (P = 0.03). The diagnostic value of C1QTNF1 was comparable to that of alpha-fetoprotein (AFP) (area under the curve [AUC] = 0.84; sensitivity 85%; specificity 80%). Furthermore, our research indicated that platelet-expressed C1QTNF1 is involved in cancer-associated signaling pathways. Our findings introduce a novel perspective by highlighting C1QTNF1 as the pivotal biomarker at the tipping point of primary HCC formation using DNB. We propose C1QTNF1 as a prognostic biomarker for HCC, potentially influencing tumor development through a platelet-related cancer signaling pathway.

 

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Dynamic network biomarker C1QTNF1 regulates tumor formation at the tipping point of hepatocellular carcinoma

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Published

16-03-2024

Data Availability Statement

The data supporting the findings of this study are available from the corresponding authors upon reasonable request. 

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Section

Translational and Clinical Research

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How to Cite

1.
Dynamic network biomarker C1QTNF1 regulates tumor formation at the tipping point of hepatocellular carcinoma. Biomol Biomed [Internet]. 2024 Mar. 16 [cited 2024 Jun. 26];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/10103