Cancer Stem Cell Markers—Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis

Abstract

Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients’ clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10−3; p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10−3). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response.

Cancer Stem Cells from Definition to Detection and Targeted Drugs

“…The median overall survival in the high-risk group was 9.1 months longer than in the low-risk group in a multivariate model based on CSC marker expression. The expression of ALDH1A1, CD44, EpCAM, LGR5, POU5F1, and THY1 in OC was proposed to predict treatment response and serve as prognostic markers for future outcomes [135].…”

A Recipe for Successful Metastasis: Transition and Migratory Modes of Ovarian Cancer Cells

“…Recently, it has been shown that both normal ovaries and fallopian tubes and ovarian tumors at different stages of tumorigenesis contain various stem cell populations [135,136] The best-known markers of ovarian CSCs include CD44, CD133, CD24, CD117, Nestin, Nanog, and Oct3/4, as well as ALDH1A1 and ABC transporters. Their expression may indicate tumor chemoresistance, a tumor-initiating potential, invasiveness, and a poor prognosis [137].…”

Clinicopathological significance of cancer stem cell marker CD44/SOX2 in esophageal squamous cell carcinoma (ESCC) patients and construction of a nomogram to predict overall survival

“…Numerous studies have indicated that heightened CD44 expression can escalate the tumorigenic potential in various cancers such as colorectal ( 12 ), breast ( 13 ) and gastric ( 14 ) cancers. Moreover, CD44 is extensively overexpressed in other cancer types like ovarian cancer ( 15 ) and oral squamous carcinoma ( 16 ), in which it is associated with aggressive biological behavior leading to a poor prognosis.…”