Kunhabdulla Hafeeda, Manas Ram, Shettihalli Ashok Kumar, Reddy Ch Ram Mohan, Mustak Mohammed S, Jetti Raghu, Abdulla Riaz, Sirigiri Divijendranatha Reddy, Ramdan Deden, Ammarullah Muhammad Imam
Department of Oral Pathology, Yenepoya Dental College, Yenepoya (Deemed to be University), Deralakatte, Mangalore 575018, India.
Department of Biotechnology, B.M.S. College of Engineering, Bull Temple Road, Bengaluru 560019, India.
ACS Omega. 2024 Mar 7;9(11):12602-12610. doi: 10.1021/acsomega.3c07206. eCollection 2024 Mar 19.
Head and neck squamous cell carcinoma (HNSCC) is one of the major types of cancer, with 900,000 cases and over 400,000 deaths annually. It constitutes 3-4% of all cancers in Europe and western countries. As early diagnosis is the key to treating the disease, reliable biomarkers play an important role in the precision medicine of HNSCC. Despite treatments, the survival rate of cancer patients remains unchanged, and this is mainly due to the failure to detect the disease early. Thus, the objective of this study is to identify reliable biomarkers for head and neck cancers for better healthcare management. In this study, all available, curated human genes were screened for their expression against HNSCC TCGA patient samples using genomic and proteomic data by various bioinformatic approaches and datamining. Docking studies were performed using AutoDock or online virtual screening tools for identifying potential ligands. Sixty genes were short-listed, and most of them show a consistently higher expression in head and neck patient samples at both the mRNA and the protein level. Irrespective of human papillomavirus (HPV) status, all of them show a higher expression in cancer samples. The higher expression of 30 genes shows adverse effects on patient survival. Out of the 60 genes, 12 genes have crystal structures and druggable potential. We show that genes such as GTF2H4, HAUS7, MSN, and MNDA could be targets of Pembrolizumab and Nivolumab, which are approved monoclonal antibodies for HNSCC. Sixty genes are identified as potential biomarkers for head and neck cancers based on their consistent and statistically significantly higher expression in patient samples. Four proteins have been identified as potential drug targets based on their crystal structure. However, the utility of these candidate genes has to be further tested using patient samples.
头颈部鳞状细胞癌(HNSCC)是主要的癌症类型之一,每年有90万例病例,死亡人数超过40万。它在欧洲和西方国家占所有癌症的3%-4%。由于早期诊断是治疗该疾病的关键,可靠的生物标志物在HNSCC的精准医疗中发挥着重要作用。尽管进行了治疗,但癌症患者的生存率仍未改变,这主要是由于未能早期检测到该疾病。因此,本研究的目的是识别头颈部癌症的可靠生物标志物,以实现更好的医疗管理。在本研究中,通过各种生物信息学方法和数据挖掘,利用基因组和蛋白质组数据,针对HNSCC TCGA患者样本筛选了所有可用的、经过整理的人类基因的表达情况。使用AutoDock或在线虚拟筛选工具进行对接研究,以识别潜在的配体。筛选出了60个基因,其中大多数在头颈部患者样本的mRNA和蛋白质水平上均表现出持续较高的表达。无论人乳头瘤病毒(HPV)状态如何,它们在癌症样本中的表达均较高。30个基因的高表达对患者生存有不良影响。在这60个基因中,有12个基因具有晶体结构和可成药潜力。我们发现,诸如GTF2H4、HAUS7、MSN和MNDA等基因可能是派姆单抗和纳武单抗的靶点,这两种药物是已获批用于HNSCC的单克隆抗体。基于在患者样本中一致且具有统计学显著意义的高表达,60个基因被鉴定为头颈部癌症的潜在生物标志物。基于其晶体结构,4种蛋白质被鉴定为潜在的药物靶点。然而,这些候选基因的效用还需要使用患者样本进一步测试。