J Cancer 2017; 8(16):3331-3342. doi:10.7150/jca.18955

Research Paper

Correlation of ALDH1 and Notch3 Expression: Clinical implication in Ovarian Carcinomas

Mi Joung Kim1*, A-Ram Kim2*, Ju-Yeon Jeong1, Kwang-il Kim1, 3, Tae-Heon Kim1, 3, Chan Lee5, Kwanghoe Chung4, Young-Hyeh Ko6, Hee-Jung An1, 3✉

1. Institute for Clinical Research, College of Medicine, CHA University, Yatap-dong, Seongnam Si Bundang-gu, Gyeonggi-Do 463-712, Republic of Korea;
2. Department of Biomedical Science, College of Life Science, College of Medicine, CHA University, Yatap-dong, Seongnam Si Bundang-gu, Gyeonggi-Do 463-712, Republic of Korea;
3. Department of Pathology, College of Medicine, CHA University, Yatap-dong, Seongnam Si Bundang-gu, Gyeonggi-Do 463-712, Republic of Korea;
4. Department of Biotechnology, College of Medicine, CHA University, Yatap-dong, Seongnam Si Bundang-gu, Gyeonggi-Do 463-712, Republic of Korea;
5. Department of Gynecologic Oncology, College of Medicine, CHA University, Yatap-dong, Seongnam Si Bundang-gu, Gyeonggi-Do 463-712, Republic of Korea;
6. Department of Pathology, Samsung Medical Center, Seoul, Republic of Korea.
* These authors equally contributed for first author.

Abstract

Purpose: ALDH1 is a putative cancer stem cell marker, while the Notch signaling pathway is involved in regulation of cancer stem cell (CSC)s. This study aims to determine the expression of Notch signaling genes in ovarian CSCs, and to assess the clinical impact of expression of ALDH1 and Notch signaling genes in ovarian cancers.

Methods: We examined expression of Notch signaling genes in FACS-sorted ALDH1(+) putative ovarian CSCs and expression of ALDH1 and Notch signaling genes in 86 ovarian epithelial tumors and various ovarian cancer cell lines by real-time RT-PCR, including Notch receptors (Notch1-4), Notch ligands (Jagged1 and Jagged2), and the downstream molecule, Hes1. Furthermore, we correlated their expression with clinicopathological parameters and patient's survival in ovarian serous carcinoma (OSC)s, the most prevalent type of ovarian cancer.

Results: The higher expression levels of ALDH1 and Notch related genes, especially Notch3 were associated with CSCs and with chemoresistant OSCs and paclitaxel-resistant SKpac ovarian cancer cells. Among the Notch signaling genes, high Notch3 expression was significantly associated with all the parameters of poor prognosis, i.e., advanced stage, lymph node and distant metastases, and chemoresistance, whereas other genes were less correlated with these parameters. A combined upregulation of ALDH1 and Notch3 was an independent poor prognostic factor in OSCs.

Conclusions: ALDH1 correlates with Notch3 expression in ovarian carcinomas. ALDH1 and Notch3 overexpression is an independent poor prognostic indicator for worse patient's survival in this subset of OSCs.

Keywords: ovarian serous carcinoma, ALDH1, Notch3, cancer stem cells, prognostic indicator.

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How to cite this article:
Kim MJ, Kim AR, Jeong JY, Kim Ki, Kim TH, Lee C, Chung K, Ko YH, An HJ. Correlation of ALDH1 and Notch3 Expression: Clinical implication in Ovarian Carcinomas. J Cancer 2017; 8(16):3331-3342. doi:10.7150/jca.18955. Available from http://www.jcancer.org/v08p3331.htm