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全癌分析结合实验验证表明,[此处原文缺失具体内容]是一种免疫和预后生物标志物。

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

作者信息

Ouyang Yan, Shen Yu, Lai Shengming, Huang Haiyan, Huang Yongsheng, Ren Shuwei

机构信息

Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

Transl Cancer Res. 2024 Nov 30;13(11):5830-5844. doi: 10.21037/tcr-24-752. Epub 2024 Nov 27.

Abstract

BACKGROUND

Kinectin 1 () is a membrane protein involved in intracellular organelle motility. However, the role of 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 .

METHODS

The expression of 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 were performed on GEPIA2.0. We investigated the protein expression level of in tumors through UALCAN. The cBioportal platform was used to analyze the variation frequency and type of . 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 knockdown.

RESULTS

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

CONCLUSIONS

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

摘要

背景

驱动蛋白连接蛋白1(Kinectin 1,KTN1)是一种参与细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估。本研究的目的是通过对KTN1进行泛癌分析来评估其在人类癌症中的表达谱及临床价值。

方法

在TIMER2.0中分析KTN1的表达及其与癌症相关成纤维细胞(CAFs)浸润的相关性。在GEPIA2.0上对KTN1进行生存分析、病理分期相关性分析及共表达基因相关性分析。通过UALCAN研究肿瘤中KTN1的蛋白表达水平。利用cBioportal平台分析KTN1的变异频率和类型。使用STRING数据库进行蛋白质-蛋白质相互作用(PPI)网络分析。进行细胞计数试剂盒-8(CCK8)、集落形成及Transwell实验,以研究敲低KTN1后对头颈部鳞状细胞癌(HNSC)细胞增殖和迁移能力的影响。

结果

与相应正常组织相比,KTN1在12种癌组织中差异表达。同时,KTN1的高表达与HNSC、肾上腺皮质癌(ACC)和肝细胞肝癌(LIHC)的预后呈负相关。进一步分析表明,在几种癌症中,携带KTN1突变的患者比未携带突变患者的总生存期(OS)和无进展生存期更好。此外,在12种癌症中,CAFs水平与KTN1表达显著相关。从机制上讲,共表达分析显示KTN1与KTN1反义RNA 1(KTN1-AS1)、细胞周期蛋白依赖性激酶激活激酶的MNAT1亚基(MNAT1)、N-α-乙酰基转移酶30(NAA30)、蛋白磷酸酶2调节亚基Bε(PPP2R2E)和蛋白酶体26S亚基(PSMC3)呈正相关,这些主要参与调节肿瘤进展的蛋白激酶AMP激活催化亚基α1(PRKAA1)信号通路。

结论

功能实验表明,KTN1促进HNSC细胞的增殖和转移。对KTN1进行的泛癌分析揭示了其在不同癌症中的意义,为癌症的诊断和预后提供了新的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/780d/11651810/c01b190e36b4/tcr-13-11-5830-f1.jpg

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