AUTHOR=Zhou Yongying , Wang Xiao , Zhang Weibing , Liu Huiyong , Liu Daoquan , Chen Ping , Xu Deqiang , Liu Jianmin , Li Yan , Zeng Guang , Li Mingzhou , Wu Zhonghua , Zhang Yingao , Wang Xinghuan , DiSanto Michael E. , Zhang Xinhua 

TITLE=The Immune-Related Gene HCST as a Novel Biomarker for the Diagnosis and Prognosis of Clear Cell Renal Cell Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.630706

DOI=10.3389/fonc.2021.630706

ISSN=2234-943X

ABSTRACT=<p>Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor worldwide. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases showed that the immune-related gene (IRG) hematopoietic cell signal transducer (HCST) could provide guidance for the diagnosis, prognosis, and treatment of ccRCC. The RNA-seq data of ccRCC tissues were extracted from two databases: TCGA (<ext-link ext-link-type="uri" xlink:href="https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga</ext-link>) and GEO (<ext-link ext-link-type="uri" xlink:href="https://www.ncbi.nlm.nih.gov/geo/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.ncbi.nlm.nih.gov/geo/</ext-link>). Corresponding clinical information was downloaded from TCGA. Immune-related gene data were extracted from the IMMPORT website (<ext-link ext-link-type="uri" xlink:href="https://www.immport.org/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.immport.org/</ext-link>). Differential analysis with R software (<ext-link ext-link-type="uri" xlink:href="https://www.r-project.org/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.r-project.org/</ext-link>) was used to obtain a prognosis model of ccRCC IRGs. The differences were combined with the clinical data to assess the usefulness of the HCST as a prognostic biomarker. Based on data obtained from the Oncomine (<ext-link ext-link-type="uri" xlink:href="https://www.oncomine.org/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.oncomine.org/</ext-link>), Human Protein Atlas (<ext-link ext-link-type="uri" xlink:href="https://www.proteinatlas.org/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.proteinatlas.org/</ext-link>), and PubMed (<ext-link ext-link-type="uri" xlink:href="https://pubmed.ncbi.nlm.nih.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">https://pubmed.ncbi.nlm.nih.gov/</ext-link>) databases, the expression levels of the HCST in ccRCC, clinical-pathological indicators of relevance, and influence on prognosis were analyzed. Regulation of the HCST gene in ccRCC was assessed by gene set enrichment analysis (GSEA). In TCGA/GEO databases, the high HCST expression in tumor tissues was significantly correlated to the TMN stage, tumor grade, invasion depth, and lymphatic metastasis (<italic>p</italic> &lt; 0.05). The overall survival (OS) of patients with high HCST gene expression was significantly lower than that of patients with low HCST gene expression (<italic>p</italic> &lt; 0.001). Multivariate Cox regression analysis suggested that the HCST expression level [hazard ratio (HR) = 1.630, 95% confidence interval (CI) = 1.042–2.552], tumor cell grade (HR = 1.829, 95% CI = 1.115–3.001), and distant metastasis (HR = 2.634, 95%, CI = 1.562–4.442) were independent risk factors affecting the OS of ccRCC patients (all, <italic>p</italic> &lt; 0.05). The GSEA study showed that there was significant enrichment in cell adhesion, tumorigenesis, and immune and inflammatory responses in HCST high expression samples. Hematopoietic cell signal transducer expression was closely associated with the levels of infiltrating immune cells around ccRCC tissues, especially dendritic cells (DCs). In conclusion, the present study suggested that the HCST was interrelated to the clinicopathology and poor prognosis of ccRCC. High HCST expression was also closely correlated with the levels of tumor-infiltrating immune cells, especially DCs.</p>