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. 2022 Feb 5;14(3):809.
doi: 10.3390/cancers14030809.

AKR1B1 as a Prognostic Biomarker of High-Grade Serous Ovarian Cancer

Marko Hojnik  1   2 , Nataša Kenda Šuster  3   4 , Špela Smrkolj  3   4 , Damjan Sisinger  2 , Snježana Frković Grazio  5 , Ivan Verdenik  3 , Tea Lanišnik Rižner  1
Affiliations

AKR1B1 as a Prognostic Biomarker of High-Grade Serous Ovarian Cancer

Marko Hojnik et al. Cancers (Basel). .

Abstract

Although aldo-keto reductases (AKRs) have been widely studied in cancer, no study to date has examined the roles of AKR family 1 members B1 (AKR1B1) and B10 (AKR1B10) in a large group of ovarian cancer patients. AKR1B1 and AKR1B10 play a significant role in inflammation and the metabolism of different chemotherapeutics as well as cell differentiation, proliferation, and apoptosis. Due to these functions, we examined the potential of AKR1B1 and AKR1B10 as tissue biomarkers. We assessed the immunohistochemical levels of AKR1B1 and AKR1B10 in tissue paraffin sections from 99 patients with high-grade serous ovarian cancer (HGSC) and compared these levels with clinicopathological characteristics, survival, and response to chemotherapy. A higher immunohistochemical AKR1B1 expression correlated with a better overall and disease-free survival of HGSC patients whereas AKR1B10 expression did not show any significant differences. A multivariant Cox analysis demonstrated that a high AKR1B1 expression was an important prognostic factor for both overall and disease-free survival. However, AKR1B1 and AKR1B10 were not associated with different responses to chemotherapy. Our data suggest that AKR1B1 is involved in the pathogenesis of HGSC and is a potential prognostic biomarker for this cancer.

Keywords: aldo-keto reductase family 1 member B1 (AKR1B1); aldo-keto reductase family 1 member B10 (AKR1B10); biomarker; high-grade serous ovarian cancer; immunohistochemistry; prognosis; resistance; survival.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemical staining of AKR1B1 and AKR1B10 in high-grade serous ovarian cancer. The graph shows the numbers of cases with the associated percentages of positive cancer cells. AKR1B1: aldo-keto reductase family 1 member B1; AKR1B10: aldo-keto reductase family 1 member B10; IQR: interquartile range; n: number of patients.
Figure 2
Figure 2
Representative immunohistochemical AKR1B1 staining in HGSC samples and control tissue. (a–d) HGSC; (e) control liver tissue; (f) control endometrioid endometrial cancer. Upper half of panels: 50 × magnification; lower half of panels: the framed area from the upper half of the panel (200 × magnification). AKR1B1: aldo-keto reductase family 1 member B1; HGSC: high-grade serous ovarian cancer.
Figure 3
Figure 3
Representative hematoxylin and eosin staining of the same samples as shown in Figure 2. (a–d) HGSC; (e) control liver tissue; (f) control endometrioid endometrial cancer. Upper half of panels: 50 × magnification; lower half of panels: the framed area from the upper half of the panel (200 × magnification). HGSC: high-grade serous ovarian cancer.
Figure 4
Figure 4
Representative immunohistochemical AKR1B10 staining in HGSC samples and control tissue. (a–d) HGSC; (e) control liver tissue; (f) control endometrioid endometrial cancer. Upper half of panels: 50 × magnification; lower half of panels: the framed area from the upper half of the panel (200 × magnification). AKR1B10: aldo-keto reductase family 1 member B10; HGSC: high-grade serous ovarian cancer.
Figure 5
Figure 5
Representative hematoxylin and eosin staining of the same samples as shown in Figure 4. (a–d) HGSC; (e) control liver tissue; (f) control endometrioid endometrial cancer. Upper half of panels: 50 × magnification; lower half of panels: the framed area from the upper half of the panel (200 × magnification). HGSC: high-grade serous ovarian cancer.
Figure 6
Figure 6
Overall and disease-free survival of patients with HGSC in relation to AKR1B1. (a) Overall survival (p = 0.006) and (b) disease-free survival curves (p = 0.002). The X-axis represents the percentages of AKR1B1-positive cancer cells. The Y-axis represents the hazard ratio for death (a) and disease relapse (b). AKR1B1: aldo-keto reductase family 1 member B1; HGSC: high-grade serous ovarian cancer.
Figure 7
Figure 7
Overall survival and disease-free survival of patients with HGSC in relation to AKR1B10. (a) Overall survival (p = 0.72) and (b) disease-free survival curves (p = 0.82). The X-axis represents the percentages of AKR1B10-positive cancer cells. The Y-axis represents the hazard ratio for death (a) and disease relapse (b). AKR1B10: aldo-keto reductase family 1 member B10; HGSC: high-grade serous ovarian cancer.
Figure 8
Figure 8
(a) AKR1B1 and (b) AKR1B10 distributions between patients with HGSC and different responses to chemotherapy. Median values, boxes from the 25th to 75th percentiles, and whiskers that correspond with the 25th percentile minus 1.5 times the interquartile range and with the 75th percentile plus 1.5 times the interquartile range are shown. ° represents mild outliers; * represents extreme outliers; AKR1B1: aldo-keto reductase family 1 member B1; AKR1B10: aldo-keto reductase family 1 member B10; IQR: interquartile range; HGSC: high-grade serous ovarian cancer.
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