A macropinocytosis-related gene signature predicts the prognosis and immune microenvironment in hepatocellular carcinoma.
A macropinocytosis-related gene signature predicts the prognosis and immune microenvironment in hepatocellular carcinoma.
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DOI：
10.3389/fonc.2023.1143013
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发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
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作者：
肝细胞癌（HCC）是一种常见的人类恶性肿瘤，生存率低，现有的治疗方法仍然不令人满意。巨胞饮症（MPC）是一种内吞作用，涉及溶解分子的非特异性摄取，已被证明有助于HCC病理；然而，其生物学机制尚不清楚。本研究利用生物信息学技术从71个候选基因中鉴定出27个巨噬细胞增多症相关基因（MRGs）。通过筛选HCC患者的标准化mRNA表达数据，并使用各种方法验证模型的可靠性并指示免疫活性，使用R软件创建预后签名模型。通过LASSO Cox回归，使用7个mpc相关差异表达基因GSK3B、AXIN1、RAC1、KEAP1、EHD1、GRB2和SNX5构建预后特征。通过这些基因的表达及其相应系数获得风险评分。发现和验证队列中的HCC患者被分层，两个队列中低风险评分患者的生存率均有所提高。随时间变化的ROC分析表明，该模型的预测信度在短期内最高。随后的免疫学分析，包括KEGG，将差异表达基因的免疫作用通路定位在肿瘤通路方向等。免疫浸润和免疫检查点试验为后续实验提供了有价值的指导。构建MRGs风险模型，有效预测HCC患者预后，提示疾病过程中免疫微环境的变化。研究结果将有利于HCC预后分层和治疗策略的发展。
Available treatments for hepatocellular carcinoma (HCC), a common human malignancy with a low survival rate, remain unsatisfactory. Macropinocytosis (MPC), a type of endocytosis that involves the non-specific uptake of dissolved molecules, has been shown to contribute to HCC pathology; however, its biological mechanism remains unknown. The current study identified 27 macropinocytosis-related genes (MRGs) from 71 candidate genes using bioinformatics. The R software was used to create a prognostic signature model by filtering standardized mRNA expression data from HCC patients and using various methods to verify the reliability of the model and indicate immune activity. The prognostic signature was constructed using seven MPC-related differentially expressed genes, GSK3B, AXIN1, RAC1, KEAP1, EHD1, GRB2, and SNX5, through LASSO Cox regression. The risk score was acquired from the expression of these genes and their corresponding coefficients. HCC patients in the discovery and validation cohorts were stratified, and the survival of low-risk score patients was improved in both cohorts. Time-dependent ROC analysis indicated that the model’s prediction reliability was the highest in the short term. Subsequent immunologic analysis, including KEGG, located the immune action pathway of the differentially expressed genes in the direction of the cancer pathway, etc. Immune infiltration and immune checkpoint tests provided valuable guidance for future follow-up experiments. A risk model with MRGs was constructed to effectively predict HCC patient prognoses and suggest changes in the immune microenvironment during the disease process. The findings should benefit the development of a prognostic stratification and treatment strategy for HCC.
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影响因子：
16.6
作者：
Zhang MS;Cui JD;Lee D;Yuen VW;Chiu DK;Goh CC;Cheu JW;Tse AP;Bao MH;Wong BPY;Chen CY;Wong CM;Ng IO;Wong CC
通讯作者：
Wong CC
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
3.7
作者：
Petrizzo A;Mauriello A;Tornesello ML;Buonaguro FM;Tagliamonte M;Buonaguro L
通讯作者：
Buonaguro L
影响因子：
50.3
作者：
Nakagawa S;Wei L;Song WM;Higashi T;Ghoshal S;Kim RS;Bian CB;Yamada S;Sun X;Venkatesh A;Goossens N;Bain G;Lauwers GY;Koh AP;El-Abtah M;Ahmad NB;Hoshida H;Erstad DJ;Gunasekaran G;Lee Y;Yu ML;Chuang WL;Dai CY;Kobayashi M;Kumada H;Beppu T;Baba H;Mahajan M;Nair VD;Lanuti M;Villanueva A;Sangiovanni A;Iavarone M;Colombo M;Llovet JM;Subramanian A;Tager AM;Friedman SL;Baumert TF;Schwarz ME;Chung RT;Tanabe KK;Zhang B;Fuchs BC;Hoshida Y;Precision Liver Cancer Prevention Consortium
通讯作者：
Precision Liver Cancer Prevention Consortium
p62-Keap1-NRF2 通路的激活可防止肝细胞癌细胞中的铁死亡。
DOI：
10.1002/hep.28251
发表时间：
2016-01
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Sun X;Ou Z;Chen R;Niu X;Chen D;Kang R;Tang D
通讯作者：
Tang D