Clinical significance and immune infiltration analyses of a novel coagulation-related signature in ovarian cancer

• Published in: Cancer cell international Vol. 23; no. 1; pp. 1 - 232
• Main Authors: Yang, Jiani, Wang, Chao, Zhang, Yue, Cheng, Shanshan, Wu, Meixuan, Gu, Sijia, Xu, Shilin, Wu, Yongsong, Sheng, Jindan, Voon, Dominic Chih-Cheng, Wang, Yu
• Format: Journal Article
• Language: English
• Published: London BioMed Central 06.10.2023; BMC
• Subjects: Algorithms; Anticoagulants; Antigens; Cancer therapies; CD38 antigen; Chemotherapy; Clinical significance; Coagulation; Datasets; DNA microarrays; Genes; Genomes; Genomics; Immune microenvironment; Immunotherapy; Infiltration; Malignancy; Medical prognosis; Metastases; Microenvironments; Nomograms; Ovarian cancer; Patients; Prognosis; Prognosis signature; Software; Thrombosis; Transcriptomes; Tumors
• DOI: 10.1186/s12935-023-03040-3
• ISSN: 1475-2867

Ovarian cancer (OV) is the most lethal gynecological malignancies worldwide. The coagulation cascade could induce tumor cell infiltration and contribute to OV progression. However, coagulation-related gene (CRG) signature for OV prognosis hasn’t been determined yet. In this study, we evaluated the prognostic value of coagulation scores through receiver operating characteristics (ROC) analysis and K-M curves, among OV patients at our institution. Based on the transcriptome data of TCGA-OV cohort, we stratified two coagulation-related subtypes with distinct differences in prognosis and tumor immune microenvironment (p < 0.05). Moreover, from the 6406 differentially-expressed genes (DEGs) between the GTEx (n = 180) and TCGA-OV cohorts (n = 376), we identified 138 potential CRGs. Through LASSO-Cox algorithm, we finally distinguished a 3-gene signature (SERPINA10, CD38, and ZBTB16), with promising prognostic ability in both TCGA (p < 0.001) and ICGC cohorts (p = 0.040). Stepwise, we constructed a nomogram based on the clinical features and coagulation-related signature for overall survival prediction, with the C-index of 0.6761, which was evaluated by calibration curves. Especially, based on tissue microarrays analysis, Quantitative real-time fluorescence PCR (qRT-PCR), and Western Blot, we found that aberrant upregulation of CRGs was related to poor prognosis in OV at both mRNA and protein level (p < 0.05). Collectively, the coagulation-related signature was a robust prognostic biomarker, which could provide therapeutic benefits for chemotherapy/immunotherapy and assist clinical decision in OV patients.