关键词: KRT80 LUAD RT-qPCR. bioinformatics analysis lung adenocarcinoma predictive biomarker

来  源:   DOI:10.2174/0113862073294339240603103623

Abstract:
BACKGROUND: According to the 2022 Global Cancer Statistics, lung cancer is the leading cause of cancer-related mortality worldwide. Lung adenocarcinoma (LUAD), which is a histological subtype of Non- Small Cell Lung Cancer (NSCLC), accounts for 40% of primary lung cancer. Therefore, there is an urgent need to identify new prognostic markers as clinical predictive markers for LUAD.
OBJECTIVE: This study aimed to investigate the role of Keratin 80 (KRT80) in the prognosis of LUAD and its underlying mechanisms.
METHODS: Bioinformatics analysis was conducted using data retrieved from The Cancer Genome Atlas (TCGA) databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were employed to predict the involved biological processes and signaling pathways, respectively. The LinkedOmics database was utilized to identify differentially expressed genes (DEGs) correlated with KRT80. Nomograms and Kaplan-Meier plots were constructed to evaluate the survival outcomes of patients diagnosed with LUAD. Moreover, TIMER was employed to conduct correlation analyses between KRT80 expression and immune cell infiltration, shedding light on the intricate interplay between KRT80 and the tumor microenvironment in LUAD. To ascertain the RNA and protein expression levels of KRT80 in LUAD and adjacent normal tissues, Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry techniques were employed, respectively.
RESULTS: Scrutiny of the TCGA dataset revealed KRT80 up-regulation across pan-cancer tissues, notably elevated in LUAD compared to healthy lung tissues. This finding was validated in our clinical samples, where Kaplan-Meier survival curves indicated poorer survival rates for high KRT80 expression in LUAD. A positive correlation was found between the transcription level of KRT80 in LUAD samples and clinical parameters, such as lymph node metastasis stage, distant metastasis, and pathological stage. Survival, logistic regression, and Cox regression analyses emphasized the clinical prognostic significance of high KRT80 expression in LUAD. Nomogram results underscored the robust predictive potential of KRT80 for the survival of LUAD patients. Gene functional enrichment analyses mainly associated KRT80 with cytokine-cytokine receptor interactions, cell cycle, apoptosis, and chemokine signaling pathways. Based on the results of the immune infiltration analysis, it can be found that the expression of KRT80 is related to the immune cell subsets and survival rate of patients with LUAD.
CONCLUSIONS: Our research revealed a significant upregulation of KRT80 in LUAD, with heightened KRT80 expression correlating with unfavorable prognosis. This study represents a comprehensive and systematic evaluation of KRT80 expression in LUAD, encompassing its prognostic and diagnostic significance, as well as underlying mechanisms. Our findings suggest that KRT80 may emerge as a novel prognostic and predictive biomarker in LUAD.
摘要:
背景:根据2022年全球癌症统计数据,肺癌是全球癌症相关死亡的主要原因。肺腺癌(LUAD),非小细胞肺癌(NSCLC)的组织学亚型,占原发性肺癌的40%。因此,迫切需要鉴定新的预后标志物作为LUAD的临床预测标志物.
目的:本研究旨在探讨角蛋白80(KRT80)在LUAD预后中的作用及其机制。
方法:使用从癌症基因组图谱(TCGA)数据库检索的数据进行生物信息学分析。基因本体论(GO)和京都基因和基因组百科全书(KEGG)数据库被用来预测所涉及的生物过程和信号通路,分别。LinkedOmics数据库用于鉴定与KRT80相关的差异表达基因(DEGs)。构建列线图和Kaplan-Meier图以评估诊断为LUAD的患者的生存结果。此外,采用TIMER对KRT80表达与免疫细胞浸润进行相关性分析,揭示了LUAD中KRT80与肿瘤微环境之间复杂的相互作用。确定KRT80在LUAD和邻近正常组织中的RNA和蛋白表达水平,采用逆转录定量聚合酶链反应(RT-qPCR)和免疫组织化学技术,分别。
结果:对TCGA数据集的审查显示,整个泛癌组织中的KRT80上调,与健康肺组织相比,LUAD显著升高。这一发现在我们的临床样本中得到了验证,其中Kaplan-Meier存活曲线表明LUAD中KRT80高表达的存活率较差。LUAD样本中KRT80的转录水平与临床参数呈正相关。如淋巴结转移分期,远处转移,和病理阶段。生存,逻辑回归,Cox回归分析强调了LUAD中KRT80高表达的临床预后意义。列线图结果强调了KRT80对LUAD患者生存的强大预测潜力。基因功能富集分析主要将KRT80与细胞因子-细胞因子受体相互作用相关,细胞周期,凋亡,和趋化因子信号通路。根据免疫浸润分析的结果,可以发现KRT80的表达与LUAD患者的免疫细胞亚群和生存率有关。
结论:我们的研究揭示了LUAD中KRT80的显著上调,升高的KRT80表达与不良预后相关。这项研究代表了对LUAD中KRT80表达的全面和系统的评估,包括其预后和诊断意义,以及潜在的机制。我们的研究结果表明,KRT80可能成为LUAD中一种新的预后和预测性生物标志物。
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