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

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.