Qiu Yuting, Li Haobo, Xie Jiaheng, Qiao Xinwei, Wu Jing
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Centre for Digestive Diseases, Beijing, 100050, People's Republic of China.
Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100029, People's Republic of China.
Int J Gen Med. 2021 Oct 27;14:7235-7246. doi: 10.2147/IJGM.S333904. eCollection 2021.
Liver cancer is the fifth most common type of cancer worldwide, and the ATP-binding cassette (ABC) transporter family has been widely accepted as a cause of multidrug resistance. This study was conducted to explore the potential value and mechanisms of the ABC transporter gene family in the liver hepatocellular carcinoma (LIHC).
Data were collected from different public databases. UALCAN, ONCOMINE, and GEPIA were used to retrieve a selection of differently expressed and pathological stage-related genes among the ABC family. Principal component analysis (PCA) was utilized for grouping, and its prognostic value was evaluated by univariate and multivariate Cox analyses. The co-expression pattern was constructed with UALCAN, and the functional analyses were carried out with DAVID. The correlation between the biomarker and immune infiltration, genetic alteration frequency, and drug sensitivity were explored with TIMER, cBioPortal, GDSC and CTRP, respectively. Finally, tSNE algorithm was used to explore the distribution of ABCC5 expressed cells.
Among the ABC transporter family members, ABCC5 was differently expressed and strongly related to the pathological stage of LIHC. PCA divided patients of LIHC into two groups, and Cox analyses demonstrated that ABCC5 was an independent risk factor of LIHC. Functional analyses indicated that the genes were enriched in the pathways of transmembrane transporter, ATPase activity, and bile secretion. ABCC5 is also associated with immune infiltration of cells like macrophages, neutrophils, and dendritic cells. The genetic alteration frequency of ABCC5 confirmed its potential value in LIHC. In addition, several drugs were explored and found to be relevant to LIHC. The t-SNE showed that expression of ABCC5 was most concentrated in macrophages, followed by hepatocytes.
ABCC5 may facilitate LIHC progression through different mechanisms and be a potential biomarker and target for diagnosis, prognosis, and therapy of LIHC.
肝癌是全球第五大常见癌症类型，ATP结合盒（ABC）转运蛋白家族已被广泛认为是多药耐药的原因。本研究旨在探讨ABC转运蛋白基因家族在肝细胞肝癌（LIHC）中的潜在价值及机制。
从不同公共数据库收集数据。利用UALCAN、ONCOMINE和GEPIA检索ABC家族中差异表达及与病理分期相关的基因。采用主成分分析（PCA）进行分组，并通过单因素和多因素Cox分析评估其预后价值。用UALCAN构建共表达模式，用DAVID进行功能分析。分别用TIMER、cBioPortal、GDSC和CTRP探讨生物标志物与免疫浸润、基因改变频率及药物敏感性之间的相关性。最后，用tSNE算法探讨ABCC5表达细胞的分布。
在ABC转运蛋白家族成员中，ABCC5差异表达且与LIHC的病理分期密切相关。PCA将LIHC患者分为两组，Cox分析表明ABCC5是LIHC的独立危险因素。功能分析表明这些基因在跨膜转运、ATP酶活性和胆汁分泌途径中富集。ABCC5还与巨噬细胞、中性粒细胞和树突状细胞等细胞的免疫浸润有关。ABCC5的基因改变频率证实了其在LIHC中的潜在价值。此外，还探索了几种与LIHC相关的药物。t-SNE显示ABCC5的表达最集中在巨噬细胞中，其次是肝细胞。
ABCC5可能通过不同机制促进LIHC进展，是LIHC诊断、预后和治疗的潜在生物标志物及靶点。
