Actin-like Protein 6A Expression Correlates with Cancer Stem Cell-like Features and Poor Prognosis in Ovarian Cancer

Po-Ming Chen; Chui-Nguk Wong; Chui-Na Wong; Pei-Yi Chu

doi:10.3390/ijms24032016

Actin-like Protein 6A Expression Correlates with Cancer Stem Cell-like Features and Poor Prognosis in Ovarian Cancer

Int J Mol Sci. 2023 Jan 19;24(3):2016. doi: 10.3390/ijms24032016.

Authors

Po-Ming Chen¹, Chui-Nguk Wong², Chui-Na Wong², Pei-Yi Chu^{3

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Affiliations

¹ Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
² Department of Obstetrics and Gynecology, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
³ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, Taiwan.
⁴ Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
⁵ School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242, Taiwan.
⁶ National Institute of Cancer Research, National Health Research Institute, Tainan 704, Taiwan.

Abstract

Ovarian cancer has the highest mortality rate among gynecological cancers, often diagnosed at the late stage and lacking an effective targeted therapy. Although the study of malignant features of cancer, considered to be cancer stem cells (CSCs), is emerging, the aim of this study was to predict and explore the possible mechanism and clinical value of genetic markers in the development of ovarian cancer from a combined database with CSCs features. The common differentially expressed genes (DEGs) were selected in GSE185833 and GSE176246 datasets from the Gene Expression Omnibus (GEO). The GSE185833 dataset was created to reveal gene expression profiles of peritoneal metastasis tissues using single-cell sequencing, and the GSE176246 dataset was determined from gene expression profiles of chemotherapy-refractory ovarian cancer cell lines compared with ovarian cancer cell lines by RNA-seq analysis. By analyzing the correlation between common DEGs and prognosis of ovarian cancer and its possible pathways and functions were predicted by The Cancer Genome Atlas (TCGA) database. The expression levels of 11 genetic markers were significantly elevated in highly invasive and chemoresistant ovarian cancer. The expression of Actin-like protein 6A (ACTL6A) was found to be correlated with survival prognosis, and the total survival time of the patients with high expression of ACTL6A was shorter than those with low expression. Gene set enrichment analysis (GSEA) showed that ACTL6A positively enriched the gene set of 'Cell cycle' and ACTL6A negatively enriched the gene set of focal adhesion. CP724714, a human epidermal growth factor receptor 2 (HER2) inhibitor, could serve as a therapeutic option when ACTL6A levels are high in ovarian cancer cells. The high expression of ACTL6A is a poor prognostic factor in ovarian cancer and may serve as an effective biomarker for predicting treatment-refractory, metastasis, and prognosis of patients with ovarian cancer. The use of HER2 inhibitors is a promising therapeutic strategy against chemoresistant ovarian cancer.

Keywords: ACTL6A; cell cycle; metastasis; ovarian cancer; prognosis; resistance.

MeSH terms

Actins* / metabolism
Chromosomal Proteins, Non-Histone / metabolism
DNA-Binding Proteins / metabolism
Female
Genetic Markers
Humans
Neoplastic Stem Cells / metabolism
Ovarian Neoplasms* / metabolism
Prognosis
Transcription Factors / genetics

Substances

Actins
ACTL6A protein, human
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
Genetic Markers
Transcription Factors

Grants and funding

This work was supported funded by grants SRD-109023 and RD107063 from Show Chwan Memorial Hospital and Ministry of Science and Technology (MOST), as well as MOST 106-2314-B-442-001-MY3 (C.P.Y.), MOST 109-2314-B-442-001 (C.P.Y.).