Abstract
Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis. 5-methylcytosine (m5C) modification plays a nonnegligible role in tumor pathogenesis and progression. However, little is known about the role of m5C regulators in HCC. Methods: Based on 9 m5C regulators, the m5C modification patterns of HCC samples extracted from public databases were systematically evaluated and correlated with tumor immune and prognosis characteristics. An integrated model called the “m5Cscore” was constructed using principal component analysis, and its prognostic value was evaluated. Results: Almost all m5C regulators were differentially expressed between HCC and normal tissues. Through unsupervised clustering, three different m5Cclusters were ultimately uncovered; these clusters were characterized by differences in prognosis, immune cell infiltration, and pathway signatures. The m5Cscore was constructed to quantify the m5C modifications of individual patients. Subsequent analysis revealed that the m5Cscore was an independent prognostic factor of HCC and could be a novel indicator to predict the prognosis of HCC. Conclusion: This study comprehensively explored and systematically profiled the features of m5C modification in HCC. m5C modification patterns play a crucial role in the tumor immune microenvironment (TIME) and prognosis of HCC. The m5Cscore provides a more holistic understanding of m5C modification in HCC and provides a practical tool for predicting the prognosis of HCC. This study will help clinicians identify effective indicators of HCC to improve the poor prognosis of this disease.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is currently the third leading cause of cancerrelated death worldwide (Bray et al, 2018; Islami et al, 2021)
We revealed three distinct m5C modification patterns in HCC; these clusters were characterized by differences in prognosis, immune cell infiltration, and pathway signatures
The results revealed that almost all enrolled m5C regulators were differentially expressed between HCC and normal tissues, while there was no difference in the expression of TET2 (Figure 1A)
Summary
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is currently the third leading cause of cancerrelated death worldwide (Bray et al, 2018; Islami et al, 2021) Effective measures such as HBV vaccine immunization and health education have been implemented, the incidence of HCC has increased from 46.3 per 100,000 to 62.8 per 100,000 between 2005 and 2014 (Bosetti et al, 2014; Sayiner et al, 2017; Hester et al, 2020). Relevant studies reported that its sensitivity was approximately 60%, and more worryingly, its specificity was 80% (Marrero et al, 2009; Lok et al, 2010) Other tumor markers, such as angiopoietin 2 or vascular endothelial growth factor, might refine prognostic prediction in statistical modeling, but cannot yet be incorporated into the individual assessment of a specific patient (Forner et al, 2018). Little is known about the role of m5C regulators in HCC
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