Integrative analysis deciphers the heterogeneity of cancer-associated fibroblast and implications on clinical outcomes in ovarian cancers

Yan Zhao; Song Mei; Yixuan Huang; Junru Chen; Xinlei Zhang; Peng Zhang

doi:10.1016/j.csbj.2022.11.025

Integrative analysis deciphers the heterogeneity of cancer-associated fibroblast and implications on clinical outcomes in ovarian cancers

Comput Struct Biotechnol J. 2022 Nov 14:20:6403-6411. doi: 10.1016/j.csbj.2022.11.025. eCollection 2022.

Authors

Yan Zhao¹, Song Mei², Yixuan Huang³, Junru Chen⁴, Xinlei Zhang³, Peng Zhang^{5

6}

Affiliations

¹ Beijing Tongren Hospital, Capital Medical University and Beijing Institute of Otolaryngology, Beijing, China.
² Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³ Beijing Cloudna Technology Co., Ltd., Beijing, China.
⁴ Institute of Chinese Medical Sciences, University of Macau, Macau, China.
⁵ Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
⁶ University of Maryland School of Medicine, Baltimore, MD, USA.

Abstract

Accumulating evidence has recognized that cancer-associated fibroblasts (CAFs) are major players in the desmoplastic stroma of ovarian cancer, modulating tumor progression and therapeutic response. However, it is unclear regarding the signatures of CAFs could be utilized to predict the clinical outcomes of ovarian cancer patients. To fill in this gap, we explored the intratumoral compartment of ovarian cancer by analyzing the single-cell RNA-sequencing (scRNA-seq) datasets of ovarian carcinoma samples, and identified two distinct CAFs (tumor-promoting CAF_c1 subtype and myofibroblasts-like CAF_c2 subtype). The clinical significance of CAF subtypes was further validated in The Cancer Genomics Atlas (TCGA) database and other independent immunotherapy response datasets, and the results revealed that the patients with a higher expression of CAF_c1 signatures had a worse prognosis and showed a tendency of resistance to immunotherapy. This work uncovered the signatures of the CAF_c1 subtype that could serve as a novel prognostic indicator and predictive marker for immunotherapy.

Keywords: BRCA, Breast invasive carcinoma; Bio-marker; CAFs; CAFs, Cancer-associated fibroblasts; COAD, Colon adenocarcinoma; ESCA, Esophageal carcinoma; Gene signature; HGSOC, High-grade serous ovarian carcinoma; HNSC, Head and neck squamous cell carcinoma; Immunotherapy; LUAD, Lung adenocarcinoma; LUSC, Lung squamous cell carcinoma; OV, Ovarian serous cystadenocarcinoma; Ovarian cancer; Prognosis; SKCM, Skin cutaneous melanoma; Single-cell sequencing; TCGA, The Cancer Genomics Atlas; THCA, Thyroid cancer; UCEC, Uterine corpus endometrial carcinoma; scRNA-seq, Single-cell RNA-sequencing.