Manipulation of Interleukin-6 (IL-6) and Transforming Growth Factor Beta-1(TGFβ-1) towards viral induced liver cancer pathogenesis

• Published in: PloS one Vol. 17; no. 10; p. e0275834
• Main Authors: Badshah, Yasmin, Shabbir, Maria, Khan, Khushbukhat, Fatima, Maha, Majoka, Iqra, Aslam, Laiba, Munawar, Huda
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 10.10.2022; Public Library of Science (PLoS)
• Subjects: Algorithms; Amino acids; Binding sites; Biology and life sciences; Breast cancer; Cell cycle; Colorectal cancer; Computer applications; Cytokines; Disease; Gene polymorphism; Genes; Genotype & phenotype; Genotypes; Growth factors; Hepatitis C; Hepatocellular carcinoma; Infections; Interleukin 6; Liver; Liver cancer; Malignancy; Medicine and Health Sciences; Mutation; Older people; Pathogenesis; Pathogenicity; Pathogens; Patients; Physical Sciences; Polymorphism; Population; Prostate cancer; Protein structure; Proteins; Sample size; Statistical analysis; Structural stability; Transcription factors; Viral infections; United States > US; Pakistan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0275834

Hepatocellular carcinoma (HCC) is the most common liver malignancy. Early diagnosis of HCC has always been challenging. This study aims to assess the pathogenicity and the prevalence of IL-6 -174G/C (rs1800795) and TGFβ-1 +29C/T (rs1800470) polymorphisms in HCV-infected HCC patients. Experimental strategies are integrated with computational approaches to analyse the pathogenicity of the TGFβ-1 +29C/T and IL-6–174 G/C polymorphisms in HCV-induced HCC. AliBaba2 was used to predict the effect of IL-6–174 G/C on transcription factor binding site in IL-6 gene. Structural changes in the mutant TGFβ-1 structure were determined through project HOPE. To assess the polymorphic prevalence of IL-6 -174G/C and TGFβ-1 +29C/T genotypes in HCC and control subjects, amplification refractory mutation system PCR (ARMS-PCR) was performed on 213 HCC and 216 control samples. GraphPad Prism version 8.0 was used for the statistical analysis of the results. In-silico analysis revealed the regulatory nature of both IL-6 -174G/C and TGFβ-1 +29C/T polymorphisms. ARMS-PCR results revealed that the individuals carrying TT genotype for TGFβ-1 gene have an increased risk of developing HCC (p<0.0001, OR = 5.403, RR = 2.062) as compared to individuals with CT and CC genotype. Similarly, GC genotype carriers for IL-6 gene exhibit an increased risk of HCC susceptibility (p<0.0001, OR = 2.276, RR = 1.512) as compared to the people carrying the GG genotype. Genotype TT of TGFβ-1 gene and genotype GC of IL-6 gene are found to be associated with HCV-induced HCC. IL-6 polymorphism may alter its transcription that leads to its pathogenicity. TGFβ-1 polymorphism may alter protein structure stability.