Ring finger protein 215 is a potential prognostic biomarker involved in immune infiltration and angiogenesis in colorectal cancer

The prognostic value of ring finger protein 215 (RNF215) in colorectal cancer (CRC) is unclear. Herein, the present study aimed to investigate the precise value of RNF215 based on CRC datasets from The Cancer Genome Atlas (TCGA) and clinical cases. CRC patient data was collected from TCGA and clinical samples from the Department of Pathology, Shanghai Fifth People's Hospital, Fudan University (Shanghai, China). Logistic regression analysis was used to investigate the correlations between RNF215 and clinicopathological characteristics. The predictive value of RNF215 for the clinical outcome of CRC was determined using Kaplan-Meier curves and Cox regression. Gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA), and angiogenesis analysis were also conducted to investigate the biological role of RNF215. Immunohistochemistry was conducted to validate the results. The results of the present study confirmed that RNF215 protein expression was significantly associated with age, lymphatic invasion, and overall survival (OS). Univariate analysis showed that upregulation of RNF215 in CRC was significantly associated with age and lymphatic invasion. Kaplan-Meier survival analysis revealed that high RNF215 expression predicted poorer OS and disease-specific survival. A total of nine experimentally detected RNF215-binding proteins were identified with the STRING tool and Cytoscape software. GSEA suggested that RNF215 was associated with several important pathways involved in tumor occurrence, including the Kyoto Encyclopedia of Genes and Genomes MAPK signaling pathway and the WikiPathway RAS signaling pathway. ssGSEA confirmed that RNF215 was significantly expressed in natural killer cells, CD8 T cells and T helper cells. Angiogenesis analysis revealed that numerous angiogenesis-related genes had the same expression trend as RNF215 in CRC. The immunostaining results indicated that RNF215 expression was significantly higher in CRC tissues than in corresponding normal tissues. In conclusion, increased RNF215 expression may be a potential molecular marker predictive of poor survival and a treatment target in CRC. In addition, RNF215 may participate in the formation of CRC through a variety of signaling pathways.

[1]  Delin Chen,et al.  Ring Finger Protein 215 Negatively Regulates Type I IFN Production via Blocking NF-κB p65 Activation , 2022, The Journal of Immunology.

[2]  Wanqing Chen,et al.  Cancer statistics in China and United States, 2022: profiles, trends, and determinants , 2022, Chinese medical journal.

[3]  Jie Liu,et al.  Decreased E2F2 Expression Correlates with Poor Prognosis and Immune Infiltrates in Patients with Colorectal Cancer , 2022, Journal of Cancer.

[4]  M. Molloy,et al.  Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps , 2021, Cancers.

[5]  Feng Yang,et al.  Hypoxia Constructing the Prognostic Model of Colorectal Adenocarcinoma and Related to the Immune Microenvironment , 2021, Frontiers in Cell and Developmental Biology.

[6]  Songbing He,et al.  Genome variation in colorectal cancer patient with liver metastasis measured by whole-exome sequencing. , 2021, Journal of gastrointestinal oncology.

[7]  Chuanyong Liu,et al.  Mex3a promotes oncogenesis through the RAP1/MAPK signaling pathway in colorectal cancer and is inhibited by hsa‐miR‐6887‐3p , 2021, Cancer communications.

[8]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[9]  Y. Ouyang,et al.  Multiregion single‐cell sequencing reveals the transcriptional landscape of the immune microenvironment of colorectal cancer , 2021, Clinical and translational medicine.

[10]  Nadezhda T. Doncheva,et al.  The STRING database in 2021: customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets , 2020, Nucleic Acids Res..

[11]  A. Quaas,et al.  Cell type‐specific transcriptomics of esophageal adenocarcinoma as a scalable alternative for single cell transcriptomics , 2020, Molecular oncology.

[12]  K. Pereira,et al.  Loss of heterozygosity and immunoexpression of PTEN in oral epithelial dysplasia and squamous cell carcinoma. , 2019, Experimental and molecular pathology.

[13]  G. Lippi,et al.  Concise update on colorectal cancer epidemiology. , 2019, Annals of translational medicine.

[14]  Zu-hua Gao,et al.  Histologic features and genomic alterations of primary colorectal adenocarcinoma predict growth patterns of liver metastasis , 2019, World journal of gastroenterology.

[15]  Jiabao Ma,et al.  Characterization of a prognostic four-gene methylation signature associated with radiotherapy for head and neck squamous cell carcinoma , 2019, Molecular medicine reports.

[16]  Amit Merchea,et al.  Rising Proportion of Young Individuals With Rectal and Colon Cancer , 2018, Clinical colorectal cancer.

[17]  Jianxin You,et al.  Molecular mechanisms of viral oncogenesis in humans , 2018, Nature Reviews Microbiology.

[18]  Adrian V. Lee,et al.  An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics , 2018, Cell.

[19]  R. Wolff,et al.  The MAPK-Signaling Pathway in Colorectal Cancer: Dysregulated Genes and Their Association With MicroRNAs , 2018, Cancer informatics.

[20]  C. Langefeld,et al.  Genome‐Wide Association Meta‐Analysis Reveals Novel Juvenile Idiopathic Arthritis Susceptibility Loci , 2017, Arthritis & rheumatology.

[21]  F. Hoppe-Seyler,et al.  The HPV E6/E7 Oncogenes: Key Factors for Viral Carcinogenesis and Therapeutic Targets. , 2017, Trends in microbiology.

[22]  A. Gozdzicka-Jozefiak,et al.  Insulin-like growth factor (IGF) axis in cancerogenesis. , 2017, Mutation research. Reviews in mutation research.

[23]  S. Stain,et al.  Local and systemic Th17 immune response associated with advanced stage colon cancer. , 2017, The Journal of surgical research.

[24]  K. Simon Colorectal cancer development and advances in screening , 2016, Clinical interventions in aging.

[25]  A. Jemal,et al.  Cancer statistics in China, 2015 , 2016, CA: a cancer journal for clinicians.

[26]  K. Thiel,et al.  NEDD4 ubiquitin ligase is a putative oncogene in endometrial cancer that activates IGF-1R/PI3K/Akt signaling. , 2015, Gynecologic oncology.

[27]  Fátima Sánchez-Cabo,et al.  GOplot: an R package for visually combining expression data with functional analysis , 2015, Bioinform..

[28]  W. Pao,et al.  Old Habits Die Hard: Addiction of BRAF-Mutant Cancer Cells to MAP Kinase Signaling. , 2015, Cancer discovery.

[29]  Matthew E. Ritchie,et al.  limma powers differential expression analyses for RNA-sequencing and microarray studies , 2015, Nucleic acids research.

[30]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[31]  Z. Trajanoski,et al.  Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. , 2013, Immunity.

[32]  Justin Guinney,et al.  GSVA: gene set variation analysis for microarray and RNA-Seq data , 2013, BMC Bioinformatics.

[33]  W. Kozlowski,et al.  K-Ras gene mutation status as a prognostic and predictive factor in patients with colorectal cancer undergoing irinotecan- or oxaliplatin-based chemotherapy , 2012, Cancer biology & therapy.

[34]  Guangchuang Yu,et al.  clusterProfiler: an R package for comparing biological themes among gene clusters. , 2012, Omics : a journal of integrative biology.

[35]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[36]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[37]  M. Grigorian,et al.  The Multifaceted S100A4 Protein in Cancer and Inflammation. , 2019, Methods in molecular biology.

[38]  Christian von Mering,et al.  STRING: a database of predicted functional associations between proteins , 2003, Nucleic Acids Res..