Fig. 1: Downregulation of MARK3 is associated with poor clinical outcome in patients with HGSOC. | Communications Biology

Fig. 1: Downregulation of MARK3 is associated with poor clinical outcome in patients with HGSOC.

From: The metabolic stress-activated checkpoint LKB1-MARK3 axis acts as a tumor suppressor in high-grade serous ovarian carcinoma

Fig. 1

a Schematic of in silico integrative analysis to identify HGSOC-associated dysregulated genes. MARK3 is downregulated in HGSOCs across two microarray datasets and one RNA-seq data set, and low MARK3 mRNA expression is associated with poor clinical outcomes in the TCGA HGSOC cohort. b–d mRNA expression levels of MARK3 (b), MAF (c), and BNC1 (d) in two independent microarray datasets. GSE18521 and GSE26712 offer microarray data of human ovarian surface epithelial cell (HOSE) samples and HGSOC samples [GSE18521(HOSE: n = 10, HGSOC: n = 53) and GSE26712 (HOSE: n = 10, HGSOC: n = 185)]. Statistical analysis was performed using an unpaired Student’s t-test. e Kaplan–Meier survival curves classified by high (n = 128) or low (n = 297) MARK3 mRNA expression in the TCGA HGSOC cohort. Low MARK3 group exhibits poor overall survival (left) and poor disease-free survival (right). f Platinum-resistant HGSOCs (n = 90) have lower MARK3 mRNA expression compared to platinum-sensitive HGSOCs (n = 197). Error bars represent mean ± standard deviation (SD). Statistical analysis was performed using an unpaired Student’s t-test. g, h RT-qPCR shows that MARK3 expression is downregulated in ovarian cancer cell lines [comparison between control (n = 3) and ovarian cancer cell line (n = 9)] (g) and the HGSOC tissues [ovary (n = 6), fallopian tube (n = 5) and HGSOC (n = 49)] (h). Ovarian cancer cell lines with HGSOC-like genetic profile, such as TP53 mutation and hyper CNA are included in this experiment. Error bars represent mean ± SD from three biological replicates. Statistical analysis was performed using an unpaired Student’s t-test. i Immunoblotting shows that MARK3 expression is downregulated in ovarian cancer cell lines compared to that in 293T cells (non-OvCa; non-Ovarian Carcinoma). j Immunohistochemistry displays that MARK3 is ubiquitously expressed in human fallopian tube secretory epithelial cells (HFTSECs) and serous tubal intraepithelial carcinomas (STICs), whereas its expression is diminished in primary HGSOCs. The expression of LKB1 is clearly decreased in STICs (arrow). p53 is used as a positive marker for STICs (arrow) and HGSOCs. Scale bars, 100 μm.

Back to article page