Ovarian cancer is one of the major causes of death in females globally. According to 2018 global cancer statistics, 295,414 new cases and 184,799 deaths were reported(1). In gynecological oncology, ovarian cancer is less prevalent than breast cancer and cervix cancer, however the death rate of OC is the highest(1). The most recent 2020 cancer statistics in United States also confirmed that ovarian cancer is the fifth cause of deaths of females (13,940 patients, 5% of total cancer-related death), only trailing by lung & bronchus cancer, breast cancer, colon & rectum cancer, and pancreas cancer(2). According to the NIH Surveillance, Epidemiology, and End Results program (SEER) survival statistics (2009–2015), 5-year survivorship of ovarian cancer is only 47.6%(3), which remained virtually unchanged since the last decade(4).
Based on the immunohistological variation, serous ovarian cancer is the most common subtype of ovarian cancer, which could be further categorized as high-grade and low-grade neoplasm according to tumor Federation International of Gynecology and Obstetrics (FIGO) grade(5, 6). High-grade serous ovarian cancer (HSOC) is the most common, aggressive, and fatal type of ovarian cancer. Almost 30% of patients died within five years of diagnosis(7), mainly because of lack of disease-specific symptoms, prominent biomarkers, and effective therapy or targeted drugs(8–10). Despite sharing some similar histological characters and terminology, high- and low- grade SOCs are now acknowledged as two different neoplasms (11). In 2011, the Cancer Genome Atlas (TCGA) program published the genomic and transcriptomic data of ovarian serous carcinoma, which summarized specific features of HSOC such as TP53 mutation, extensive DNA copy variation, BRCA1/BRCA2 inactive mutation, CCNE1 aberrations, and other survival-related preliminary transcriptional signatures (12–15).
Fibroblast activation protein (FAP), a cell-surface serine protease, emerges as an imperative factor in cancer-associated fibroblasts (CAFs), especially relevant to tumor occurrence and progression. Structurally, FAP consists of a cytoplasmic tail, a single transmembrane domain, and an extracellular domain(16). FAP is rarely expressed in healthy adult tissues. However, FAP is usually highly upregulated during tissue remodeling events, including cancers or cancer-associated fibroblasts (CAFs)(17–20). In addition, FAP is considered as a potential biomarker in certain tumor diagnosis and progression due to its protumorigenic specificity in both enzymatic and non-enzymatic manners (21–24).
In this study, we aim to identify potential biomarkers of HSOC survival from TCGA ovarian cancer cohort bioinformatics data. We analyzed gene expression, clinical and/or demographic information, and targeted strategies for potential HSOC biomarkers. In addition, we validated our findings by immunohistological investigation of tissues in a group of Chinese HSOC patients. Results suggest that FAP expression could be an effective biomarker for HSOC survival, which warrants further investigation as potential intervention of HSOC.