Draškovič Tina, Ranković Branislava, Zidar Nina, Hauptman Nina
Institute of Pathology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.
Genes (Basel). 2024 Nov 28;15(12):1545. doi: 10.3390/genes15121545.
Altered gene expression in cancers holds great potential to improve the diagnostics and differentiation of primary and metastatic liver cancers. In this study, the expression of the protein-coding genes ring finger protein 135 (), ephrin-B2 (), ring finger protein 125 (), homeobox-C 4 (), actin-binding LIM protein 1 () and oncostatin M receptor () and the long non-coding RNAs (lncRNA) prospero homeobox 1 antisense RNA 1 () and leukemia inhibitory factor receptor antisense RNA 1 () was investigated in hepatocellular carcinoma, cholangiocarcinoma, colorectal liver metastases and pancreatic ductal adenocarcinoma liver metastases.
This study included 149 formalin-fixed, paraffin-embedded samples from 80 patients. After RNA isolation, quantification, reverse transcription and preamplification, real-time qPCR was performed. The gene expression between different groups was calculated relative to the expression of the reference genes using the ∆∆Cq method and statistically analyzed. The expression of the genes was additionally analyzed using the AmiCA and UCSC Xena platforms.
In primary cancers, our results showed differential expression between primary tumors and healthy tissues for all the genes and lncRNA examined. Moreover, we found downregulation of in hepatocellular carcinoma, downregulation of in colorectal liver metastases and upregulation of in cholangiocarcinoma compared to primary liver cancers and metastatic cancers. The major finding is the upregulation of in cholangiocarcinoma compared to hepatocellular carcinoma, colorectal liver metastases, pancreatic ductal adenocarcinoma liver metastases and healthy liver tissue. We propose as a potential biomarker that differentiates cholangiocarcinoma from other cancers and healthy liver tissue.
This study emphasizes the importance of understanding the differences in gene expression between healthy tissues and primary and metastatic cancers and highlights the potential use of altered gene expression as a diagnostic biomarker in these malignancies.
癌症中基因表达的改变在改善原发性和转移性肝癌的诊断及鉴别方面具有巨大潜力。在本研究中，我们调查了编码蛋白基因环指蛋白135（RNF135）、ephrin-B2（EFNB2）、环指蛋白125（RNF125）、同源盒C4（HOXC4）、肌动蛋白结合LIM蛋白1（ABLIM1）和制瘤素M受体（OSMR）以及长链非编码RNA（lncRNA）prospero同源盒1反义RNA1（PROX1-AS1）和白血病抑制因子受体反义RNA1（LIFR-AS1）在肝细胞癌、胆管癌、结直肠癌肝转移和胰腺导管腺癌肝转移中的表达情况。
本研究纳入了来自80例患者的149份福尔马林固定、石蜡包埋样本。在进行RNA分离、定量、逆转录和预扩增后，进行实时定量聚合酶链反应（qPCR）。使用∆∆Cq法计算不同组之间相对于参考基因表达的基因表达量，并进行统计学分析。此外，还使用AmiCA和UCSC Xena平台对基因表达进行了分析。
在原发性癌症中，我们的结果显示，所有检测的基因和lncRNA在原发性肿瘤与健康组织之间存在差异表达。此外，与原发性肝癌和转移性癌症相比，我们发现肝细胞癌中RNF135表达下调，结直肠癌肝转移中EFNB2表达下调，胆管癌中HOXC4表达上调。主要发现是，与肝细胞癌、结直肠癌肝转移、胰腺导管腺癌肝转移和健康肝组织相比，胆管癌中PROX1-AS1表达上调。我们提出PROX1-AS1作为一种潜在的生物标志物，可将胆管癌与其他癌症及健康肝组织区分开来。
本研究强调了了解健康组织与原发性和转移性癌症之间基因表达差异的重要性，并突出了基因表达改变作为这些恶性肿瘤诊断生物标志物的潜在用途。
