Research Paper Volume 15, Issue 20 pp 11286—11297

STK4 is a prognostic biomarker correlated with immune infiltrates in clear cell renal cell carcinoma

Zi-Yuan Bai2, *, , Lu-Shan Peng1,3,4,5, *, , Run-Qi Li3, , Xianchu Peng3, , Zhe Yang2, ,

  • 1 Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
  • 2 Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan, China
  • 3 School of Basic Medicine, Central South University, Changsha 410031, Hunan, China
  • 4 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
  • 5 Key Laboratory of Hunan Province in Neurodegenerative Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China
* Equal contribution

Received: July 11, 2023       Accepted: October 2, 2023       Published: October 20, 2023      

https://doi.org/10.18632/aging.205127
How to Cite

Copyright: © 2023 Bai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) is a highly conserved serine/threonine kinase and a central member of the Hippo signaling pathway. STK4 has been reported to play important roles in various tumors, but a systematic and comprehensive study of its function in clear cell renal cell carcinoma (ccRCC) has not been conducted.

Methods: In this study, we used immunohistochemistry (IHC), western blot (WB), quantitative real-time PCR (qPCR) experiments, and bioinformatics analysis to comprehensively analyze the expression, prognostic value, and immune infiltration of STK4 in ccRCC.

Results: Analysis of the TCGA database showed that the expression level of the STK4 gene in ccRCC patients depended on tumor stage, grade, and distant lymphatic metastasis. This was further confirmed by the results of IHC, WB, and qPCR. In addition, we used the receiver operating characteristic curve (ROC curve) to elucidate the diagnostic value of STK4 in ccRCC patients. According to the findings of the TIMER database, the high expression of STK4 is significantly associated with the survival of kidney cancer (including ccRCC) patients (p < 0.001), suggesting that STK4 is a reliable prognostic predictor. We then used gene set enrichment analysis (GSEA) to explore the mechanisms behind STK4 function in ccRCC. We found that STK4 may play a role in immune regulation interactions. Subsequently, we performed immune infiltration analysis of STK4. The results showed that STK4 may regulate the development of ccRCC by affecting the immune infiltration of NK and pDC cells.

Conclusions: STK4 may be a prognostic marker for ccRCC and may help identify new strategies for treating ccRCC patients.

Abbreviations

MST1/STK4/KRS2: Mammalian STE20-like kinase 1; ccRCC: clear cell renal cell carcinoma; ACC: Adrenocortical carcinoma; BLCA: Bladder Urothelial Carcinoma; BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; HNSC: Head and Neck squamous cell carcinoma; KICH: Kidney Chromophobe; KIRC: Kidney renal clear cell carcinoma; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute Myeloid Leukemia; LGG: Brain Lower Grade Glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and Paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin Cutaneous Melanoma; STAD: Stomach adenocarcinoma; STES: Stomach and Esophageal carcinoma; TGCT: Testicular Germ Cell Tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine Corpus Endometrial Carcinoma; UCS: Uterine Carcinosarcoma; UVM: Uveal Melanoma; ROC: receiver operating characteristic; IHC: Immunohistochemistry; WB: western blot; TIMER: tumor immune estimation resource; OS: overall survival; KEGG: Encyclopedia of Genes and Genomes; GSEA: Gene set enrichment analysis.