Pan-cancer analysis combined with experimental validation revealed that KTN1 is an immunological and prognostic biomarker.

IF 1.5 4区 医学 Q4 ONCOLOGY
Translational cancer research Pub Date : 2024-11-30 Epub Date: 2024-11-27 DOI:10.21037/tcr-24-752
Yan Ouyang, Yu Shen, Shengming Lai, Haiyan Huang, Yongsheng Huang, Shuwei Ren
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引用次数: 0

Abstract

Background: Kinectin 1 (KTN1) is a membrane protein involved in intracellular organelle motility. However, the role of KTN1 in human pan-cancer lacks systematic analysis and evaluation. The aim of this study is to evaluate the expression profile and clinical value in human cancers by performing a pan-cancer analysis of KTN1.

Methods: The expression of KTN1 and its correlation with cancer-associated fibroblasts (CAFs) infiltration were analyzed in TIMER2.0. The survival analysis, pathological stage correlation, and co-expression gene correlation analysis of KTN1 were performed on GEPIA2.0. We investigated the protein expression level of KTN1 in tumors through UALCAN. The cBioportal platform was used to analyze the variation frequency and type of KTN1. We used STRING database for protein-protein interaction (PPI) network analysis. Cell Counting Kit-8 (CCK8) and colony formation and transwell assay were performed to investigate the proliferation and migration abilities of head and neck squamous cell carcinoma (HNSC) cells with KTN1 knockdown.

Results: KTN1 was differentially expressed in 12 kinds of cancer tissues compared with correspondent normal tissues. Meanwhile, the high expression of KTN1 was negatively correlated with the prognosis of HNSC, adrenocortical carcinoma (ACC), and liver hepatocellular carcinoma (LIHC). Further analysis suggested that patients with KTN1 mutations had better overall survival (OS) and progression-free survival than those without mutations among several cancers. Moreover, the level of CAFs and KTN1 expression were significantly correlated in 12 types of cancer. Mechanically, co-expression analysis showed the positive association between KTN1 and KTN1 antisense RNA 1 (KTN1-AS1), MNAT1 component of CDK activating kinase (MNAT1), N-alpha-acetyltransferase 30 (NAA30), protein phosphatase 2 regulatory subunit B'epsilon (PPP2R5E), and proteasome 26S subunit (PSMC6), which are mainly involved in the protein kinase AMP-activated catalytic subunit alpha 1 (AMPK) signaling pathway that regulates the progression of tumors.

Conclusions: The functional experiment revealed that KTN1 promotes the proliferation and metastasis of HNSC cells. The pan-cancer analysis of KTN1 revealed its significance in different cancers, which provides a new marker for the diagnosis and prognosis of cancers.

泛癌分析结合实验验证表明,KTN1是一种免疫学和预后生物标志物。
背景:运动蛋白1 (KTN1)是一种参与胞内细胞器运动的膜蛋白。然而,KTN1在人类泛癌中的作用缺乏系统的分析和评价。本研究的目的是通过对KTN1进行泛癌症分析,评估其在人类癌症中的表达谱和临床价值。方法:在TIMER2.0中分析KTN1的表达及其与癌相关成纤维细胞(CAFs)浸润的相关性。在GEPIA2.0上进行存活分析、病理分期相关性分析、KTN1共表达基因相关性分析。我们通过UALCAN检测肿瘤中KTN1蛋白的表达水平。利用cBioportal平台分析KTN1变异频率和变异类型。我们使用STRING数据库进行蛋白质-蛋白质相互作用(PPI)网络分析。采用细胞计数试剂盒-8 (CCK8)和集落形成及transwell实验研究KTN1敲低的头颈部鳞状细胞癌(HNSC)细胞的增殖和迁移能力。结果:KTN1在12种癌组织中与相应的正常组织存在差异表达。同时,KTN1高表达与HNSC、肾上腺皮质癌(ACC)、肝细胞癌(LIHC)的预后呈负相关。进一步的分析表明,在几种癌症中,KTN1突变的患者比没有突变的患者有更好的总生存期(OS)和无进展生存期。此外,在12种类型的癌症中,CAFs水平与KTN1表达显著相关。机械共表达分析显示KTN1与KTN1反义RNA 1 (KTN1- as1)、CDK活化激酶MNAT1组分(MNAT1)、n - α -乙酰转移酶30 (NAA30)、蛋白磷酸酶2调节亚基B'epsilon (PPP2R5E)、蛋白酶体26S亚基(PSMC6)呈正相关,主要参与蛋白激酶amp活化的催化亚基α 1 (AMPK)信号通路调控肿瘤进展。结论:功能实验显示KTN1促进HNSC细胞的增殖和转移。通过对KTN1的泛癌分析,揭示了其在不同肿瘤中的意义,为癌症的诊断和预后提供了新的标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.10
自引率
0.00%
发文量
252
期刊介绍: Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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