Piroozkhah Moein, Zabihi Mohammadreza, Jalali Pooya, Salehi Zahra
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Institute of Biochemistry and Biophysics (IBB), Department of Bioinformatics, Laboratory of Complex Biological Systems and Bioinformatics (CBB), University of Tehran, Tehran, Iran.
Cancer Rep (Hoboken). 2024 Dec;7(12):e70087. doi: 10.1002/cnr2.70087.
Gastrointestinal cancers (GICs) continue to dominate in terms of both incidence and mortality worldwide. Due to the absence of efficient and accurate prognostic biomarkers, the prognosis and treatment outcomes of many GICs are poor. Identifying biomarkers to predict individual clinical outcomes efficiently is a fundamental challenge in clinical oncology. Although several biomarkers have been continually discovered, their predictive accuracy is relatively modest, and their therapeutic use is restricted. In light of this, the discovery of reliable biomarkers for predicting prognosis and outcome in GIC is urgently required.
We evaluated the Human Protein Atlas dataset and identified NPC Intracellular Cholesterol Transporter 2 (NPC2) and Integrin Subunit Alpha V (ITGAV) as probable poor predictive genes for these cancers. In addition, we used the GEPIA2, cBioPortal, UALCAN, LinkedOmics, STRING, Enrichr, TISDB, TIMER2.0, hTFTarget, miRTarBase, circBank, and drug-gene interaction database databases to conduct a comprehensive and systematic analysis of the NPC2 and ITGAV genes.
Our results found high expression levels of NPC2 and ITGAV in most GICs. The aforementioned gene expressions were linked to several clinicopathological characteristics of GICs as well as poorer prognosis in LIHC and STAD. The most common alteration type of NPC2 was amplification, and for ITGAV was deep deletion. Significant promotor hypermethylation was also seen in NPC2 and ITGAV in PAAD and COAD, respectively. For the immunologic significance, NPC2 and ITGAV were positively correlated with the abundance of tumor-infiltrating lymphocytes and macrophages. Furthermore, various immunomodulators showed strong correlations with the expression of these genes. There were currently 10 small molecule drugs targeting ITGAV.
Consequently, our bioinformatics analysis showed that NPC2 and ITGAV might be used as potential biomarkers to determine the prognosis of various GICs and are also related to immune infiltration.
胃肠道癌（GICs）在全球发病率和死亡率方面仍然占据主导地位。由于缺乏高效准确的预后生物标志物，许多GICs的预后和治疗效果较差。有效识别预测个体临床结局的生物标志物是临床肿瘤学的一项基本挑战。尽管不断发现了几种生物标志物，但其预测准确性相对较低，且其治疗用途受到限制。鉴于此，迫切需要发现用于预测GIC预后和结局的可靠生物标志物。
我们评估了人类蛋白质图谱数据集，并确定NPC细胞内胆固醇转运蛋白2（NPC2）和整合素亚基αV（ITGAV）可能是这些癌症的不良预测基因。此外，我们使用GEPIA2、cBioPortal、UALCAN、LinkedOmics、STRING、Enrichr、TISDB、TIMER2.0、hTFTarget、miRTarBase、circBank和药物-基因相互作用数据库对NPC2和ITGAV基因进行了全面系统的分析。
我们的结果发现NPC2和ITGAV在大多数GICs中高表达。上述基因表达与GICs的几种临床病理特征以及LIHC和STAD中较差的预后相关。NPC2最常见的改变类型是扩增，而ITGAV是深度缺失。在PAAD和COAD中，NPC2和ITGAV分别也出现了显著的启动子高甲基化。关于免疫意义，NPC2和ITGAV与肿瘤浸润淋巴细胞和巨噬细胞的丰度呈正相关。此外，各种免疫调节剂与这些基因的表达显示出强烈的相关性。目前有10种靶向ITGAV的小分子药物。
因此，我们的生物信息学分析表明，NPC2和ITGAV可能用作确定各种GICs预后的潜在生物标志物，并且也与免疫浸润有关。
