Secreted protein acidic and rich in cysteine gene variants: Impact on susceptibility and survival of hepatocellular carcinoma patients

Abstract

Background and Aim Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein involved in extracellular matrix remodeling, which regulates cell growth. It could be involved in hepatic fibrogenesis related to chronic inflammations, hepatocellular carcinoma (HCC) angiogenesis, and tumor progression. We aimed to study the expressions of single nucleotide polymorphisms in the SPARC gene and their impact on susceptibility and survival of HCC patients. Methods We conducted a case–control study on 200 HCC patients and 50 matched healthy controls. All patients were subjected to laboratory investigations, ultrasound, and real‐time polymerase chain reaction to detect the genetic polymorphisms (rs3210714, rs11950384, and rs7719521) in the SPARC gene in the blood. Results One hundred sixty (80%) patients were men with a mean age of 43 years. The SPARC gene showed a significant higher prevalence of rs3210714 mutation (i.e. AA or AG) and a significant lower prevalence of rs11950384 mutation (i.e. AA or AC) among HCC patients in comparison with controls (83% vs 22%, P ≤ 0.001) and (65.5 vs 86%, P = 0.005), respectively, while rs7719521 mutation did not reach significance. On univariate and multivariate analyses, elder age and having at least one copy of the mutant rs3210714 were associated with a significantly increased risk of HCC (P < 0.001 for both), whereas the presence of at least one copy of the mutant rs11950384 carried a significantly reduced risk of having HCC (P < 0.01). Overall survival did not differ significantly between any of the SPARC gene mutation groups. Conclusions The SPARC gene polymorphisms had a diverse impact on the susceptibility of HCC due to its ability to inhibit or promote tumor progression. SPARC gene polymorphisms were not related to survival of our HCC patients, and probably, this needs further analysis of other SPARC gene nucleotides.

Prognostic value of SPARC in hepatocellular carcinoma: A systematic review and meta-analysis

“…HRs for reported or estimated OS and disease-free survival (DFS) with 95% CIs were included. SPARC was mentioned as a predictor of poor prognosis in four studies, and only one [ 38 ] found that it had no effect on OS. SPARC was found to be a good predictor of outcomes in one study [ 35 ].…”

“…Zhang et al recorded OS and used methylmion specific polymerase chain reaction (MSP) to determine SPARC levels in 60 samples [ 33 ]. Darweesh et al recorded OS and used qPCR to determine SPARC levels in 200 samples [ 38 ].…”

“…Darweesh et al selected patients with HCC as the study group and healthy volunteers as the control group. Healthy paticipants were those who had normal liver enzyme levels and functions, negative results on viral hepatitis screening, and normal abdominal ultrasound scans [ 38 ]. Six did not mention blinding in the outcome analysis.…”

“…Based on the title and abstract screening, 72 irrelevant articles were excluded, and 45 were further screened for assessment of eligibility. Thirty-nine studies that did not meet our inclusion criteria were excluded, leaving six [32,33,[35][36][37][38] for inclusion in the meta-analysis.…”

The Histone Variant MacroH2A1 Impacts Circadian Gene Expression and Cell Phenotype in an In Vitro Model of Hepatocellular Carcinoma

“…Another highly down-regulated gene, CDO1 (FC −60.54), encodes cysteine dioxygenase type 1 and is a tumor suppressor found silenced by promoter methylation in different cancer types, such as non-small cell lung cancer and gastrointestinal cancers, including liver cancer [49][50][51][52]. SPARC (secreted protein acidic and rich in cysteine, fold change −36.12) encodes a glycoprotein involved in extracellular matrix remodeling and influencing cell growth and hepatic fibrogenesis in chronic inflammation as well as cell proliferation, migration and invasion, angiogenesis, and tumor progression in HCC, where its decreased expression in tumor tissue predicts poorer prognosis [53][54][55]. CYP7A1 (fold change −31.38) encodes a member of the cytochrome P450 superfamily of rate-limiting monooxygenases engaged in drug metabolism, lipids/steroids/cholesterol synthesis, and cholesterol to bile acids conversion.…”