A prognostic signature based on immune-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma

• Published in: International immunopharmacology 2020-11, Vol.88, p.106884-106884, Article 106884
• Main Authors: Liu, Jinhui, Wu, Zhipeng, Wang, Yichun, Nie, Sipei, Sun, Rui, Yang, Jing, Cheng, Wenjun
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma - diagnosis; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - immunology; Algorithms; Antigens, CD - immunology; Antigens, CD1 - immunology; Antigens, Differentiation, T-Lymphocyte - immunology; Cancer; Carcinoma, Squamous Cell - diagnosis; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - immunology; CD1c antigen; CD6 antigen; Cell Line, Tumor; Cervix; CESC; Chemotherapy; Databases, Chemical; Databases, Genetic; Drug development; Drugs; ESTIMATE algorithm; Female; Gene expression; Gene Expression Regulation, Neoplastic - immunology; Genes; Genes - immunology; Genomics; Glycoproteins - immunology; Health risks; Humans; Immune checkpoint; Immune Checkpoint Proteins - metabolism; Immune microenvironment; Immune system; Immunogenicity; Immunosuppressive agents; Immunotherapy; Kaplan-Meier Estimate; Lymphocytes, Tumor-Infiltrating - metabolism; Malignancy; Microenvironments; Middle Aged; Nomograms; Patients; Prognosis; Protein Interaction Maps; Risk; Risk Factors; Risk groups; Squamous cell carcinoma; Stromal cells; Stromal Cells - metabolism; TCGA; Transcriptome - immunology; Tumor Microenvironment - immunology; Tumors; Uterine Cervical Neoplasms - diagnosis; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - immunology
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2020.106884

•The status of immune infiltration in CESC was measured by ESTIMATE algorithm.•A two-gene signature (CD1C and CD6 genes) was established to predict the prognosis of CESC based on ESTIMATE algorithm.•Two prognostic subtypes and corresponding treatment strategy were defined. Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the fourth commonest female malignancy worldwide. CESC progresses in immune-microenvironment mainly composed of infiltrating immune and stromal cells. Here, we performed an integrated analysis incorporating the expression profiles from the Cancer Genome Atlas (TCGA) database and scores of immune and stromal cells calculated by Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm. A two-gene signature (CD1C and CD6 genes) was established to predict the prognosis of CESC. Based on this signature, patients were divided into the high- and low-risk groups, and this signature showed good prognostic performance according to the results of Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis in train set and two validation sets. A nomogram was built for evaluating the clinical applicability of this signature. In addition, based on Tumor Immune Estimation Resource (TIMER) database, 2 hub genes showed negative correlations with tumor purity and positive correlations with infiltrating levels of immune filtrating cells. What’s more, we propose new treatment strategies for the two prognostic subtypes. Low- risk patients were found presenting with a higher level of immune checkpoint molecules and showing higher immunogenicity in immunophenoscore (IPS) analysis, which indicated a better response for immunotherapy. Meanwhile, estimated by Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk patients showed sensitive responses to five chemotherapy drugs. Finally, 10 candidate small-molecule drugs for CESC were defined. In summary, the CD1C-CD6 signature can accurately predict the prognosis of CESC.