Dataset Information

AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas.

ABSTRACT: The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06-0.65, p = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12-0.88, p = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer.

SUBMITTER: Hojnik M

PROVIDER: S-EPMC7766127 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas.

Hojnik Marko M Kenda Šuster Nataša N Smrkolj Špela Š Frković Grazio Snježana S Verdenik Ivan I Rižner Tea Lanišnik TL

Journal of clinical medicine 20201219 12

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malig ...[more]

PMID: 33352741

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Project description:BackgroundAdherence to National Comprehensive Cancer Network guidelines have been adopted as the standard of care for various cancers and have been cited to have survival benefits. Few studies have examined the association of adherent treatment and endometrial cancer survival among various racial/ethnic groups and socioeconomic statuses.MethodsBetween January 1, 2006 and December 31, 2015, 83,673 women diagnosed with endometrial carcinomas were identified from the Surveillance, Epidemiology, and End Results database. Descriptive statistics of demographic and clinical characteristics were performed. Cox-proportional hazards models were used to examine the effect on cause-specific survival for adherence to guidelines across racial/ethnic and socioeconomic groups.ResultsWithin our sample, 59.5% were treated according to guidelines. Nonadherence to treatment guidelines was significantly associated with decreased survival compared with adherent care (adjusted hazard ratio [HR], 1.59; 95% CI, 1.52-1.67). Being of Black (adjusted HR, 1.41; 95% CI, 1.32-1.51) or Native Hawaiian/Pacific Islander (adjusted HR, 1.44; 95% CI, 1.19-1.73) race/ethnicity compared with White women was significantly associated with worse survival. Being of Asian race/ethnicity (adjusted HR, 0.86, 95% CI, 0.78-0.94) was significantly associated with improved survival compared with White women. Lower neighborhood socioeconomic status was associated with a negative effect on survival relative to women in the highest socioeconomic status category.ConclusionsFindings from this study suggest treatment adherence is an independent predictor of improved survival; however, improved survival was not observed equally among all racial/ethnic and socioeconomic status groups.Lay summaryThe National Comprehensive Cancer Network (NCCN) has developed guidelines for physicians to follow in treating various cancers. Within this study of 83,673 women with endometrial cancer, 59.5% of women were treated according to the NCCN guidelines. The findings suggest following NCCN guidelines for treatment of endometrial cancer improves survival. Black or Native Hawaiian/Pacific Islander race and lower neighborhood socioeconomic status has worse survival rates compared with other groups, indicating the importance of exploring other factors that may shape treatment across racial/ethnic and socioeconomic status groups.

Project description:BackgroundIn recent years, sentinel lymph node excision and ultrastaging have been performed in endometrial carcinomas to obtain information about lymph node status, avoiding unnecessary complete pelvic and paraaortic lymphadenectomy. The purpose of this retrospective study was to provide a comprehensive evaluation of the pathological features of endometrial carcinomas and their significance in association with sentinel lymph node involvement.MethodsPatients with endometrial carcinomas, preceded by sentinel lymph node mapping, were classified into Group-I and Group-II with negative and positive involvement, respectively. The pathological features, associated with sentinel lymph node involvement, were statistically analyzed, including determination of test performance parameters.ResultsAmong 70 patients who had undergone hysterectomy and sentinel lymph node excision, 61 had carcinoma and 9 had atypical hyperplasia. There were 50 patients in Group-I and 10 in Group-II. In Group-II, the significant pathological features were: 1) lower uterine segment involvement (100%), 2) an average tumor size of ≥5 CM, 3) lymphovascular invasion (50%), 4) cervical stromal invasion (40%), and 5) depth of myometrial invasion of ≥50% (50%). The incidences of these pathological features were significantly less in Group-I. Statistical analyses singled out "lower uterine segment involvement" as the most important feature.ConclusionsWe have identified five pathological features which are associated with sentinel lymph node involvement. Since lower uterine segment involvement has occurred in all cases of the Group-II cohort, we recommend FIGO and other organizations that determine staging rules should consider whether tumors that involve the lower uterine segment should be staged as higher than "1a", if the findings in this small series are confirmed by other studies. The results of this study may guide pathologists and oncologists in the diagnostic and therapeutic approaches to management of endometrial carcinomas.

Project description:BACKGROUND:Women have a better melanoma prognosis, and fairer skin/hair colour. The presence of inherited MC1R variants has been associated with a better melanoma prognosis, but its interaction with sex is unknown. OBJECTIVES:To evaluate the relationship between germline MC1R status and survival, and determine any association with sex. METHODS:This was a cohort study including 1341 patients with melanoma from the Melanoma Unit of the Hospital Clinic of Barcelona, between January 1996 and April 2018. We examined known sex-related prognosis factors as they relate to features of melanoma and evaluated the sex-specific role of MC1R in overall and melanoma-specific survival. Hazard ratios (HRs) were calculated using univariate and multivariate Cox logistic regression. RESULTS:Men showed lower overall survival than women (P < 0·001) and the presence of inherited MC1R variants was not associated with better survival in our cohort. However, in women the presence of MC1R variants was associated with better overall survival in the multivariate analysis [HR 0·57, 95% confidence interval (CI) 0·38-0·85; P = 0·006] but not in men [HR 1·26, 95% CI 0·89-1·79; P = 0·185 (P-value for interaction 0·004)]. Analysis performed for melanoma-specific survival showed the same level of significance. CONCLUSIONS:Inherited MC1R variants are associated with improved overall survival in women with melanoma but not in men. Intrinsic sex-dependent features can modify the role of specific genes in melanoma prognosis. We believe that survival studies of patients with melanoma should include analysis by sex and MC1R genotype. What's already known about this topic? Inherited MC1R variants have been associated with a better melanoma prognosis, but their interaction with sex is unknown. What does this study add? MC1R variants are related to better overall survival and melanoma-specific survival in women but not in men. What is the translational message? These differences between the sexes could imply future changes in melanoma follow-up and treatment strategies. This provides a basis for understanding the interaction between sex-related genes and germline variants in cancer.

Project description:Although various factors may contribute to its initiation and progression, the etiology and prognostic factors of endometrial carcinoma (EC) remains not fully understood. We sought to understand the role of changes in transcriptome during the progress of EC by exploring public datasets. The aberrant expression characteristics of EC based on RNA-Seq and miRNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed. Kaplan-Meier analysis was performed to assess the relationship between differently expressed genes (DEGs) and patient survival. As a result, 320 out of 4,613 differently expressed mRNAs (DE mRNAs) and 68 out of 531 differently expressed miRNAs (DE miRNAs) with a significantly poorer survival were determined. We predicted eight paired DE miRNAs and DE mRNAs through TargetScan. Patients with three out of the eight paired low rate of miRNA/mRNA (miR-497/EMX1, miR-23c/DMBX1, and miR-670/KCNS1) expression had a significantly poorer survival. Furthermore, the simultaneous presence of these selected low miRNA/mRNA pairs occurred in most patients and resulted in a significantly poorer survival rate. Luciferase reporter assay identified that EMX1 was a direct target of miR-497. Both low expression of miR-497 and overexpression of EMX1 were significantly associated with more advanced clinicopathologic characteristics (stage, tumor status, grade, and histology) besides survival (all P values < 0.05). Multivariate analysis also demonstrated that miR-497 remained an independent prognostic variable for overall survival. In summary, we identified that a series of DE mRNAs and miRNAs, including eight paired DE miRNAs and mRNAs, were associated with survival in EC. Clinical evaluation of downregulated miR-497 and paired upregulated EMX1 confirmed the value of our prediction analysis. The simultaneous presence of low rate of these selected low miRNA/mRNA pairs (miR-497/EMX1, miR-23c/DMBX1, and miR-670/KCNS1) might have a better prediction value. Therefore, further studies are required to validate these findings.

Dataset Information

AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas.

Publications

AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas.

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