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

Jiani Yang; Chao Wang; Yue Zhang; Shanshan Cheng; Meixuan Wu; Sijia Gu; Shilin Xu; Yongsong Wu; Jindan Sheng; Dominic Chih-Cheng Voon; Yu Wang

doi:10.1186/s12935-023-03040-3

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

Cancer Cell Int. 2023 Oct 6;23(1):232. doi: 10.1186/s12935-023-03040-3.

Authors

Jiani Yang^{1

2}, Chao Wang^{1

2}, Yue Zhang^{1

2}, Shanshan Cheng³, Meixuan Wu³, Sijia Gu³, Shilin Xu³, Yongsong Wu³, Jindan Sheng^{1

2}, Dominic Chih-Cheng Voon^{4

5}, Yu Wang^{6

7}

Affiliations

¹ Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
² Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
³ Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
⁴ Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa, 9201192, Japan.
⁵ Institute of Frontier Sciences Initiative, Kanazawa University, Kanazawa, Ishikawa, 9201192, Japan.
⁶ Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China. renjiwangyu@126.com.
⁷ Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China. renjiwangyu@126.com.

Abstract

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.

Keywords: Coagulation; Immune microenvironment; Ovarian cancer; Prognosis signature.

Abstract

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