Roy Nabanita, Lodh Ria, Mandal Susmita, Kumar Jolly Mohit, Sarma Anupam, Bhattacharyya Dhruba Kumar, Barah Pankaj
Department of Molecular Biology and Biotechnology, Tezpur University, Napaam, Sonitpur, Assam, 784028, India.
Department of Bioengineering, Indian Institute of Science, Bangalore 560012, India.
Transl Oncol. 2025 Jan;51:102192. doi: 10.1016/j.tranon.2024.102192. Epub 2024 Nov 14.
Hepatobiliary cancers (HBCs) pose a major global health challenge, with a lack of effective targeted biomarkers. Due to their complex anatomical locations, shared risk factors, and the limitations of targeted therapies, generalized treatment strategies are often used for gallbladder cancer (GBC), hepatocellular carcinoma (HCC), and intrahepatic cholangiocarcinoma (ICC). This study aimed to identify specific transcriptomic signatures in GBC, HCC, and ICC. The transcriptomic data analysis revealed distinct expression profiles, highlighting complex molecular heterogeneity within these cancers, even within the same organ system. Functional annotation revealed distinct biological pathways associated with each type of HBCs. GBC was linked to cell cycle regulation, HCC was associated with immune system modulation, and ICC was involved in metabolic dysregulation, particularly lipid metabolism. Gene co-expression network (GCN) and protein-protein interaction (PPI) network analyses identified potential key genes, such as MAPK3 and ERBB2 in GBC, AC069287.1 and ACTN2 in HCC, and TRPC1 and BACE1 in ICC. The FOX family of transcription factors (TFs) was conserved across all three cancer types. To further explore the relationship between Epithelial-Mesenchymal Transition (EMT) and the identified hub genes and TFs, an EMT score analysis was conducted. This analysis revealed distinct phenotypic characteristics in each cancer type, with TFs identified in GBC and ICC showing a stronger correlation with EMT compared to those in HCC. External validation using The Cancer Genome Atlas (TCGA) databases confirmed the expression of candidate genes, underscoring their potential as therapeutic targets. These findings provide valuable insights into the molecular heterogeneity and complexity of HBCs, opening new avenues for personalized therapeutic interventions.
肝胆癌（HBCs）是一项重大的全球健康挑战，缺乏有效的靶向生物标志物。由于其复杂的解剖位置、共同的风险因素以及靶向治疗的局限性，胆囊癌（GBC）、肝细胞癌（HCC）和肝内胆管癌（ICC）通常采用通用的治疗策略。本研究旨在确定GBC、HCC和ICC中的特定转录组特征。转录组数据分析揭示了不同的表达谱，突出了这些癌症内部复杂的分子异质性，即使在同一器官系统内也是如此。功能注释揭示了与每种类型的HBCs相关的不同生物学途径。GBC与细胞周期调控有关，HCC与免疫系统调节有关，而ICC则参与代谢失调，尤其是脂质代谢。基因共表达网络（GCN）和蛋白质-蛋白质相互作用（PPI）网络分析确定了潜在的关键基因，如GBC中的MAPK3和ERBB2、HCC中的AC069287.1和ACTN2以及ICC中的TRPC1和BACE1。转录因子（TFs）的FOX家族在所有三种癌症类型中都是保守的。为了进一步探索上皮-间质转化（EMT）与所确定的枢纽基因和TFs之间的关系，进行了EMT评分分析。该分析揭示了每种癌症类型的不同表型特征，与HCC中的TFs相比，GBC和ICC中鉴定出的TFs与EMT的相关性更强。使用癌症基因组图谱（TCGA）数据库进行的外部验证证实了候选基因的表达，强调了它们作为治疗靶点的潜力。这些发现为HBCs的分子异质性和复杂性提供了有价值的见解，为个性化治疗干预开辟了新途径。
