Abstract

Background: Secreted protein acidic and rich in cysteine (SPARC) plays an important role in cancer development. The roles of SPARC in the liver hepatocellular carcinoma (LIHC) are unclear. Methods: GEPIA2 and UALCAN were used to analyze the SPARC mRNA expression levels in LIHC based on the TCGA database. The GEO database was used to verify the analysis results. Immunohistochemical (IHC) analysis was used to investigate the SPARC protein levels in LIHC tissues. The Kaplan–Meier (KM) plotter was used to analyze the correlation between SPARC and prognosis. The serum SPARC levels were measured by ELISA. CCK8 and murine xenograft models were used to investigate the effect of SPARC on the liver cancer growth in vitro and in vivo. SPARC-correlated genes were screened by LinkedOmics. Results: Based on the TCGA and GEO databases, the analysis showed that the SPARC mRNA expression levels were increased in tumor tissues and peripheral blood mononuclear cell (PBMC) from LIHC compared to normal controls. The IHC analysis showed an increased level of SPARC in LIHC tissues compared to adjacent non-tumor tissues. However, we found that the serum SPARC levels were lower in LIHC than those in healthy controls. The KM plotter showed that there was no significant correlation between the SPARC mRNA levels and overall survival. However, in sorafenib-treated LIHC patients, the high SPARC expression predicts favorable prognosis. Furthermore, the endogenous SPARC overexpression promotes liver cancer cell proliferation in vitro and tumor growth in vivo, while there was no significant effect of exogenous SPARC treatment on liver cancer cell proliferation. Function enrichment analysis of SPARC-correlated genes indicated a critical role of interaction with an extracellular matrix in SPARC-promoting cancer cell proliferation. Conclusion: SPARC mRNAs were increased in LIHC tumor tissues, and SPARC overexpression may promote the liver cancer growth. Further studies are needed to clarify the potential prognostic value of SPARC, both in tissues and in circulation.

Highlights

  • According to the Global Cancer Observatory (GLOBOCAN) data from 2020 (Sung et al, 2021), primary liver cancer is currently the sixth most commonly diagnosed cancer (4.7%) and the third cause of cancer death (8.3%) worldwide

  • Secreted protein acidic and rich in cysteine (SPARC) Expression Were Increased in Liver hepatocellular carcinoma (LIHC) Tissues

  • We first analyzed the SPARC expression levels in LIHC patients based on the TCGA and GEO databases

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Summary

Introduction

According to the Global Cancer Observatory (GLOBOCAN) data from 2020 (Sung et al, 2021), primary liver cancer is currently the sixth most commonly diagnosed cancer (4.7%) and the third cause of cancer death (8.3%) worldwide. Liver hepatocellular carcinoma (LIHC) is the most common subtype (75–85%) of primary liver cancer (Sung et al, 2021). SPARC has been found to play an important role in tumor progression (Tai and Tang, 2008). The studies have shown that SPARC overexpression could act as a tumor suppressor gene, which inhibits cancer proliferation, invasion, and angiogenesis in certain types of cancer, including gastric cancer (Zhang et al, 2012), medulloblastoma (Bhoopathi et al, 2010; Bhoopathi et al, 2011), ovarian cancer (Said and Motamed, 2005), and prostate cancer (Wong et al, 2007). The roles of SPARC in the liver hepatocellular carcinoma (LIHC) are unclear

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