S100P as a novel biomarker of microvascular invasion and portal vein tumor thrombus in hepatocellular carcinoma

Abstract

Background

Portal vein tumor thrombus (PVTT) and microvascular invasion (MVI) are types of intrahepatic vascular metastasis of hepatocellular carcinoma (HCC) and are highly correlated with poor prognosis. However, the underlying biomarkers of PVTT and MVI are unclear.

Methods

We identified a PVTT/MVI-associated gene S100P by cDNA microarray analysis, and assess the potential value of serum S100P measurement in the differential diagnosis of HCC and prediction of MVI status with large retrospective and perspective cohort studies.

Results

The mRNA and protein of S100P was increased in HCCs with PVTT or MVI. High S100P immunostaining in tumors was correlated with inferior tumor-free survival. Serum S100P values discriminated patients with HCCs from those with benign liver tumors, and it showed predictive potential of MVI status in both retrospective and perspective cohorts. S100P may regulate HCC tumorigenicity and invasive ability; S100P also was associated with up-regulation of CD44, which may mediate HCC cell adhesion to form PVTT/MVI.

Conclusions

Serum S100P may be a novel differential diagnostic marker for HCC and a potential predictor of MVI status pre-surgery for HCC patients. S100P overexpression in HCC is highly correlated with the formation of PVTT and MVI, which may make S100P as a potential therapeutic target for HCC metastasis.

Graphic abstract

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Funding

This work was supported by the National Nature Science Foundation of China (NSFC 81972306, 81960450, 81860502, 81502533), and Guangxi Nature Sciences Grants (2018GXNSFAA138028, 2018GXNSFAA050124, Gui Ke AB16380242). This work was also supported in part by the Guangxi BaGui Scholars Special Fund and the Guangxi Medical University Training Program for Distinguished Young Scholars.

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Authors

Contributions

Conceptualization: L-NQ, B-DX, L-QL, W-TX, Z-JJ, and Z-SC. Methodology: L-NQ, LM, F-XW, J-ZY, W-FG, and H-HL. Validation: L-NQ and F-XW. Formal analysis: L-NQ, J-JS, and Y-YC. Investigation: L-NQ and Y-YC. Resources: J-HZ, Z-SC, W-FG, and J-ZY. Data curation: L-NQ and J-HZ. Writing—original draft preparation: L-NQ, LM, and B-DX. Writing—review and editing: L-QL. Visualization: W-TX, Z-JJ, H-HL, and J-JS. Supervision: L-NQ, B-DX, and L-QL. Project administration: L-NQ. Funding acquisition: L-NQ.

Corresponding authors

Correspondence to Lu-Nan Qi or Bang-De Xiang or Le-Qun Li.

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Conflict of interest

Lu-Nan Qi declares that he has no conflict of interest. Liang Ma declares that he has no conflict of interest. Fei-Xiang Wu declares that he has no conflict of interest. Yuan-Yuan Chen declares that he has no conflict of interest. Wan-Ting Xing declares that he has no conflict of interest. Zhi-Jun Jiang declares that he has no conflict of interest. Jian-Hong Zhong declares that he has no conflict of interest. Zu-Shun Chen declares that he has no conflict of interest. Wen-Feng Gong declares that he has no conflict of interest. Jia-Zhou Ye declares that he has no conflict of interest. Hong-Hao Li declares that he has no conflict of interest. Jin-Jie Shang declares that he has no conflict of interest. Bang-De Xiang declares that he has no conflict of interest. Le-Qun Li declares that he has no conflict of interest.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Tumor Hospital of Guangxi Medical University No. LW2018035) and with the Helsinki Declaration of 1975, as revised in 2008.

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Qi, LN., Ma, L., Wu, FX. et al. S100P as a novel biomarker of microvascular invasion and portal vein tumor thrombus in hepatocellular carcinoma. Hepatol Int 15, 114–126 (2021). https://doi.org/10.1007/s12072-020-10130-1

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Keywords

  • CD44
  • Cell migration
  • Cell invasion
  • Skeleton rearrangement
  • Tumorigenicity
  • Diagnosis
  • Prognosis
  • Biomarker
  • AFP
  • Benign liver tumor
  • Early stage
  • Tumor-free survival