Decreased expression of ALDH5A1 predicts prognosis in patients with ovarian cancer

Abstract

Aldehyde dehydrogenase 5 family, member A1 (ALDH5A1) belongs to the superfamily of aldehyde dehydrogenases (ALDHs). However, the prognostic value of ALDH5A1 in ovarian cancer remains unclear. The aim of this study was to explore the relationship between ALDH5A1 and the prognosis of patients with ovarian cancer (OC). We compared the expression of ALDH5A1 in OC to that innormal controls, using GSE40595 profiling data. Tissue microarray analysis was conducted for192 OC patients, 14 adjacent normal ovary tissues, and 2 normal ovary tissues. Using the "Kaplan-Meier plotter" (KM plotter) database, updated gene expression data and survival information of a total of 1583 OC patients were used to evaluate the prognostic value of ALDH5A1 in OC patients. We found that ALDH5A1 mRNA expression was downregulated in OC patients compared with that innormal tissues. In survival analyses, we found that ALDH5A1 was positively linked to prognosis in patients with OC, particularly in those with serous ovarian cancer (SOC). In addition, high Ctranscription activity of ALDH5A1 was correlated with better overall survival in SOC patients expressing mutatedTP53, but not in those expressing wild-type TP53. In pathological grades II/III, a high mRNA level of ALDH5A1 was associated with improved overall survival. The positive association between ALDH5A1 and prognosis was found not only in early stages(I and II), but also in advanced stages (III and IV) of SOC patients. results indicate that ALDH5A1 is an excellent predictive factor of OC and may play crucial roles in OC progression.

Keywords: Aldehyde dehydrogenase 5 family member A1; Kaplan-Meier plotter; biomarker; ovarian cancer; prediction; prognosis; suvival.

Figure 1.

ALDH5A1 was downregulated in patients with ovarian tumor. (A) Comparison of ALDH5A1 expression in microdissected tumor epithelial tissues with that of microdissected normal epithelial tissues using the GSE40595 database. (B) Immunohistochemical analysis of ALDH5A1 expression in ovarian tissues. IHC score of each patient was plotted as an individual dot in the chart. (C) Ovarian tumor samples weakly positively stained with a staining index marked as +. (D) Ovarian tumor samples moderately positively stained with a staining index marked as ++. (E) Ovarian tumor samples strongly positively stained with a staining index marked as +++. (F) Normal ovarian samples strongly positively stained with a staining index marked as +++. Others. Mucinous papillary adenocarcinoma(n = 24), adenocarcinoma (n = 7), Disgerminoma (n = 5), Endodermal sinus carcinoma(n = 7), Endometrioid carcinoma(n = 3), Embryonal carcinoma (n = 1), Immature teratoma(n = 2), Mature teratoma(n = 1), Clear cell carcinoma (n = 1), Transitional cell carcinoma(n = 1), Strumal carcinoid(n = 1), Squamous cell carcinoma from teratoma with malignant transformation(n = 3), Granular cell tumor(n = 4).

Figure 2.

The prognostic effect of the ALDH5A1 mRNA level in OC was got from KM plotter (www.kmplot.com). The desired Affymetrix IDs is valid: 203608_at (ALDH5A1). Survival curves are plotted for all patients (n = 1582) (A), serous cancer patients (n = 1138) (B), endometrioid cancer patients (n = 36) (C).

Figure 3.

The prognostic effect of the expression of ALDH5A1 mRNA in www.kmplot.com. The desired Affymetrix IDs is valid: 203608_at (ALDH5A1). Survival curves are plotted for TP53 mutated cases (n = 431) (A), for TP53 wild type cases (n = 83) (B).

Figure 4.

Correlation of ALDH5A1 mRNA high expression with pathological grades of ovarian cancer patients, the prognostic effect of the expression of ALDH5A1 in www.kmplot.com. The desired Affymetrix IDs is valid: 203608_at (ALDH5A1). OS (A) and PFS (D) for cases in grade I, OS (B) and PFS (E) for cases in grade II, OS (C) and PFS (F) for cases in grade III.

Figure 5.

Correlation of ALDH5A1 mRNA high expression with clinical stages of ovarian cancer patients. The prognostic effect of the expression of ALDH5A1 in www.kmplot.com. The desired Affymetrix IDs is valid: 203608_at (ALDH5A1). OS (A) and PFS (C) for cases in stage I+II, OS (B) and PFS (D) for cases in stage III+IV.