Current status and perspectives of molecular mechanisms of gender difference in hepatocellular carcinoma: The tip of the iceberg?

IF 5.7 4区 生物学 Q1 BIOLOGY
Zhi-Quan Xu, Shi-Qiao Luo, Zhong-Jun Wu, Rui Liao
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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) risk factors and incidence vary globally, but men generally have higher incidence than women. Men also tend to have a worse prognosis in terms of survival period and pathological characteristics. Furthermore, there are notable gender differences in treatment strategies and drug responses. While traditional risk factors such as hepatitis B virus, hepatitis C virus, alcohol consumption, and metabolic syndrome contribute to these differences, the underlying molecular mechanisms remain partly understood. Recent research has focused on elucidating the roles of sex hormones, DNA damage and repair pathways, immune microenvironments, and genetic/epigenetic factors in driving gender-specific disparities. For instance, estrogen receptor signaling has been shown to suppress HCC progression, whereas androgen receptor signaling promotes tumor development. Additionally, immune cells such as tumor-associated macrophages and regulatory T cells exhibit gender-specific patterns, with males typically showing higher levels of immunosuppressive cells. Omics analyses, including genomics, transcriptomics, and proteomics, have further revealed sex-specific differences in gene expression, protein interactions, and metabolic pathways. Despite these advances, significant gaps remain in understanding the interplay between environmental, hormonal, and genetic factors in shaping gender disparities in HCC. Future research should prioritize the identification of novel molecular targets, the development of gender-specific therapeutic strategies, and the integration of multi-omics data to address these disparities. Addressing these challenges will be critical for improving diagnostic, prognostic, and therapeutic outcomes in HCC patients of both sexes.

肝细胞癌性别差异分子机制的现状与展望:冰山一角?
肝细胞癌(HCC)的危险因素和发病率在全球各不相同,但男性的发病率普遍高于女性。男性在生存期和病理特征方面也往往预后较差。此外,在治疗策略和药物反应方面存在显著的性别差异。虽然传统的危险因素,如乙型肝炎病毒、丙型肝炎病毒、饮酒和代谢综合征造成了这些差异,但潜在的分子机制仍部分被了解。最近的研究集中在阐明性激素、DNA损伤和修复途径、免疫微环境和遗传/表观遗传因素在驱动性别差异中的作用。例如,雌激素受体信号传导抑制HCC进展,而雄激素受体信号传导促进肿瘤发展。此外,免疫细胞如肿瘤相关巨噬细胞和调节性T细胞表现出性别特异性模式,男性通常表现出更高水平的免疫抑制细胞。组学分析,包括基因组学、转录组学和蛋白质组学,进一步揭示了基因表达、蛋白质相互作用和代谢途径的性别特异性差异。尽管取得了这些进展,但在HCC中形成性别差异的环境、激素和遗传因素之间的相互作用的理解上仍存在重大差距。未来的研究应优先确定新的分子靶点,发展针对性别的治疗策略,并整合多组学数据来解决这些差异。解决这些挑战对于改善男女HCC患者的诊断、预后和治疗结果至关重要。
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来源期刊
CiteScore
13.60
自引率
1.80%
发文量
47
审稿时长
>12 weeks
期刊介绍: BioScience Trends (Print ISSN 1881-7815, Online ISSN 1881-7823) is an international peer-reviewed journal. BioScience Trends devotes to publishing the latest and most exciting advances in scientific research. Articles cover fields of life science such as biochemistry, molecular biology, clinical research, public health, medical care system, and social science in order to encourage cooperation and exchange among scientists and clinical researchers.
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