Abstract
BackgroundOvarian cancer was one of the leading causes of female deaths. Patients with OC were essentially incurable and portends a poor prognosis, presumably because of profound genetic heterogeneity limiting reproducible prognostic classifications.MethodsWe comprehensively analyzed an ovarian cancer single-cell RNA sequencing dataset, GSE118828, and identified nine major cell types. Relationship between the clusters was explored with CellPhoneDB. A malignant epithelial cluster was confirmed using pseudotime analysis, CNV and GSVA. Furthermore, we constructed the prediction model (i.e., RiskScore) consisted of 10 prognosis-specific genes from 2397 malignant epithelial genes using the LASSO Cox regression algorithm based on public datasets. Then, the prognostic value of Riskscore was assessed with Kaplan–Meier survival analysis and time-dependent ROC curves. At last, a series of in-vitro assays were conducted to explore the roles of IL4I1, an important gene in Riskscore, in OC progression.ResultsWe found that macrophages possessed the most interaction pairs with other clusters, and M2-like TAMs were the dominant type of macrophages. C0 was identified as the malignant epithelial cluster. Patients with a lower RiskScore had a greater OS (log-rank P < 0.01). In training set, the AUC of RiskScore was 0.666, 0.743 and 0.809 in 1-year, 3-year and 5-year survival, respectively. This was also validated in another two cohorts. Moreover, downregulation of IL4I1 inhibited OC cells proliferation, migration and invasion.ConclusionsOur work provide novel insights into our understanding of the heterogeneity among OCs, and would help elucidate the biology of OC and provide clinical guidance in prognosis for OC patients.
Highlights
Ovarian cancer (OC) was one of the most fatal and aggressive tumors of the female reproductive system and had emerged at an increased incidence in recent years
Effort made in understanding prognosis [2, 3] and response to platinum-based chemotherapy [4,5,6] in OC was highly focused on profiling gene expression and genetic aberrations
A single‐cell atlas of ovarian cancers and control samples Eighteen samples obtained from GSE118828 were studied, namely a total of 17 neoplasms including 1 benign cancer, 1 peritoneal cancer, 3 LGSOC, 12 HGSOC, and 1 control ovarian
Summary
Ovarian cancer (OC) was one of the most fatal and aggressive tumors of the female reproductive system and had emerged at an increased incidence in recent years. Acknowledged treatment for OC is surgery followed by platinum and taxane-based combination chemotherapy. Nearly 25 percent of OC patients were found to relapse within six months after combination therapy [1]. Effort made in understanding prognosis [2, 3] and response to platinum-based chemotherapy [4,5,6] in OC was highly focused on profiling gene expression and genetic aberrations. Ovarian cancer was one of the leading causes of female deaths. Patients with OC were essentially incurable and portends a poor prognosis, presumably because of profound genetic heterogeneity limiting reproducible prognostic classifications
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