Clinicopathologic significance and race-specific prognostic association of MYB overexpression in ovarian cancer

AbstractLate diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.

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Nuclear SYK phosphorylation is associated with poor survival in high-grade serous ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2017.03.301 ◽

2017 ◽

Vol 145 ◽

pp. 129

Author(s):

Y. Yu ◽

Y. Suryo ◽

B. Davidson ◽

A.A. Africano ◽

A.N. Fader ◽

...

Keyword(s):

Ovarian Cancer ◽

High Grade ◽

Serous Ovarian Cancer ◽

Poor Survival

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Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

Endocrine Related Cancer ◽

10.1530/erc-12-0395 ◽

2013 ◽

Vol 20 (2) ◽

pp. 251-262 ◽

Cited By ~ 117

Author(s):

Catherine M Olsen ◽

Christina M Nagle ◽

David C Whiteman ◽

Roberta Ness ◽

Celeste Leigh Pearce ◽

...

Keyword(s):

Ovarian Cancer ◽

Menopausal Status ◽

Low Grade ◽

Ovarian Cancer Risk ◽

Histological Subtypes ◽

Increased Risk ◽

Modifiable Factors ◽

Menopausal Women ◽

Increase Risk ◽

Post Menopausal

Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case–control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m2; 95% CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03–1.25) and in pre-menopausal women (1.11; 1.04–1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

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Proline-rich protein 11 overexpression is associated with a more aggressive phenotype and poor overall survival in ovarian cancer patients

10.21203/rs.3.rs-35747/v2 ◽

2020 ◽

Author(s):

yu zhan ◽

xueyuan wu ◽

gang zheng ◽

jingjing jin ◽

chaofu li ◽

...

Keyword(s):

Ovarian Cancer ◽

Overall Survival ◽

Curative Surgery ◽

Poor Overall Survival ◽

Expression Levels ◽

Prognostic Assessment ◽

Therapy Strategies ◽

Proline Rich Protein

Abstract Background: The proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer. Methods: Immunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015. Results: In total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1).Conclusions: The findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.

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The forkhead box L2 transcription factor (FOXL2) is differentially expressed in high-grade serous ovarian cancers.

10.31219/osf.io/8nt6v ◽

2020 ◽

Author(s):

Shahan Mamoor

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Expression Profiles ◽

Gynecologic Cancer ◽

Ovarian Tumors ◽

High Grade ◽

Normal Ovary ◽

Primary Tumors ◽

Forkhead Box ◽

Ovarian Cancers

Ovarian cancer is the most lethal gynecologic cancer (1). We sought to identify genes associated with high-grade serous ovarian cancer (HGSC) by comparing global gene expression profiles of normal ovary with that of primary tumors from women diagnosed with HGSC using published microarray data (2, 3). We identified the forkhead box L2, (FOXL2) (4) as among the genes whose expression was most different in HGSC ovarian tumors. FOXL2 expression was significantly lower in ovarian tumors relative to normal ovary. FOXL2 has established roles in ovarian development (4, 5), and the FOXL2 gene is mutated in granulosa-cell tumors of the ovary (6). These data indicate FOXL2 might also be perturbed, at the level of gene expression, in high-grade serous ovarian cancers.

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