目前肝细胞肝癌的细胞增殖及侵袭转移机制尚未完全阐明,治疗方面也缺乏令人满意的有效方法.近年来,随着模拟基质硬度的细胞培养平台的建立和逐步改进,基质硬度等生物力学因素及其影响的研究逐渐受到重视.细胞外基质硬度的改变,可通过一系列分子机制调控细胞行为,促进肝癌细胞增殖和增强其侵袭转移能力,本文对其相关机制的研究现状进行综述,希望为肝癌治疗新靶点和新策略的开发提供线索.
Objectives The present study aimed to develop a gene signature based on the ESTIMATE algorithm in hepatocellular carcinoma (HCC) and explore possible cancer promoters. Methods The ESTIMATE and CIBERSORT algorithms were applied to calculate the immune/stromal scores and the proportion of tumor-infiltrating immune cells (TICs) in a cohort of HCC patients. The differentially expressed genes (DEGs) were screened by Cox proportional hazards regression analysis and protein–protein interaction (PPI) network construction. Cyclin B1 (CCNB1) function was verified using experiments. Results The stromal and immune scores were associated with clinicopathological factors and recurrence-free survival (RFS) in HCC patients. In total, 546 DEGs were up-regulated in low score groups, 127 of which were associated with RFS. CCNB1 was regarded as the most predictive factor closely related to prognosis of HCC and could be a cancer promoter. Gene Set Enrichment Analysis (GSEA) and CIBERSORT analyses indicated that CCNB1 levels influenced HCC tumor microenvironment (TME) immune activity. Conclusions The ESTIMATE signature can be used as a prognosis tool in HCC. CCNB1 is a tumor promoter and contributes to TME status conversion.
目的 探讨白蛋白-胆红素(ALBI)评分在肝癌治疗及预后中的应用价值.方法 对近年来发表的有关ALBI评分与肝癌相关研究的文献,如ALBI评分来源及其在预测肝癌手术治疗、肝移植及非手术治疗后患者的生存情况等方面进行综述.结果 ALBI评分是肝癌肝切除患者术后的独立预后因素,ALBI评分作为肝癌根治性肝切除后早期复发的危险因素可能有助于复发时根据患者肝功能确定适当的治疗方法;ALBI评分分级3级作为肝移植术后死亡率的独立预测因子,可能对优化肝移植的个体风险评估有帮助;ALBI评分可作为临床医生对肝癌患者在肝切除和非手术治疗之间进行选择的参考工具.结论 ALBI评分评估肝功能的作用不亚于当前广泛应用的Child-Pugh分级,它在评估肝癌患者预后及复发方面有着重要作用,有利于为肝癌患者选择个体化的治疗方式,制定使患者最大获益的治疗方案.
癌相关成纤维细胞(CAF)是肿瘤微环境中主要的基质细胞.CAF可在血小板源性生生长因子、成纤维细胞生长因子、白介素6及肝细胞生长因子等多种分泌因子作用下由正常成纤维细胞转化形成,也可由间充质干细胞、脂肪细胞等多种细胞可通过上皮间质转化(EMT)过程形成,还有部分由癌症干细胞转化而来.近来有研究显示,乳腺癌中的CAF可通过分泌多种细胞因子及外泌体、参与EMT及细胞外基质重塑,进而促进乳腺癌细胞侵袭转移,也可在肿瘤缺氧微环境下通过激活相关信号通路促进乳腺癌细胞生长和侵袭.此外,CAF通过增加了乳腺癌细胞的凋亡阈值、作为抗肿瘤药物的物理屏障、分泌的谷氨酰胺增加乳腺癌细胞的存活率、激活生长因子相关的信号通路或增加线粒体功能产生抗凋亡作用等多种途径介导乳腺癌化疗耐药、内分泌治疗耐药及多药耐药.笔者总结CAF的重要来源及其在乳腺癌侵袭转移与治疗耐药中的研究进展.
