Hajibabaie Fatemeh, Mohamadynejad Parisa, Shariati Laleh, Safavi Kamran, Abedpoor Navid
Department of Biology, ShK.C., Islamic Azad University, ShahreKord 88137-33395, Iran.
Department of Biomaterials, Nanotechnology and Tissue Engineering, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran.
Biology (Basel). 2025 Jul 2;14(7):803. doi: 10.3390/biology14070803.
PAN-gastrointestinal cancers (PAN-GI cancers), including the oral, esophageal, gastric, hepatocellular, pancreatic=, and colorectal cancers, are the leading cause of cancer-related mortality. Despite recent advances in identifying the molecular mechanisms driving these malignancies, the high incidence and recurrence of the PAN-gastrointestinal cancers and the low survival rates of patients indicate the need to introduce biomarkers for early diagnosis to improve diagnostic and therapeutic approaches. In the present study, using integrated transcriptomics, RNA-Seq and microarray data, from the TCGA and GEO databases, respectively, were combined to discover and validate a global biomarker panel for PAN-gastrointestinal cancers. In order to validate the bioinformatics data, the expression levels of genes in the molecular panel were evaluated using real-time quantitative polymerase chain reaction (qPCR) in tumor tissues of 21 patients with early diagnosis of gastric cancer and colorectal cancer (Stage I and II). By examining the transcriptomic profiles of six types of PAN-gastrointestinal cancers, a network of closely related hub genes ( = 167) with biomarker potential ( value < 0.05) was identified. Also, using ROC curve analysis and the Youden index, a molecular panel consisting of , , , and was presented (95% confidence interval and value < 0.05), which showed exceptional sensitivity and specificity in differentiating malignant tissue from normal tissue (AUC > 80%). The diagnostic efficacy of these markers was confirmed by further validation using qPCR in colorectal and gastric tumor samples ( value < 0.05). In conclusion, a novel molecular signature panel including the , , , and genes could improve early cancer detection and diagnostic accuracy, and it may contribute to the treatment outcomes of PAN-gastrointestinal cancer patients.
泛胃肠道癌（PAN-GI癌），包括口腔癌、食管癌、胃癌、肝细胞癌、胰腺癌和结直肠癌，是癌症相关死亡的主要原因。尽管在识别驱动这些恶性肿瘤的分子机制方面取得了最新进展，但PAN-胃肠道癌的高发病率和复发率以及患者的低生存率表明，需要引入生物标志物进行早期诊断，以改善诊断和治疗方法。在本研究中，分别使用来自TCGA和GEO数据库的综合转录组学、RNA测序和微阵列数据，以发现和验证用于PAN-胃肠道癌的全球生物标志物组。为了验证生物信息学数据，使用实时定量聚合酶链反应（qPCR）评估了21例早期诊断为胃癌和结直肠癌（I期和II期）的肿瘤组织中分子组中基因的表达水平。通过检查六种类型的PAN-胃肠道癌的转录组谱，确定了一个具有生物标志物潜力（P值<0.05）的密切相关的枢纽基因网络（n = 167）。此外，使用ROC曲线分析和尤登指数，提出了一个由、、和组成的分子组（95%置信区间，P值<0.05），其在区分恶性组织与正常组织方面表现出卓越的敏感性和特异性（AUC>80%）。通过在结直肠癌和胃癌样本中使用qPCR进一步验证，证实了这些标志物的诊断效力（P值<0.05）。总之，一个包括、、和基因的新型分子特征组可以提高癌症早期检测和诊断准确性，并且可能有助于PAN-胃肠道癌患者的治疗结果。
