Cytoplasmic VDR expression as an independent risk factor for ovarian cancer

Czogalla, Bastian; Deuster, Eileen; Liao, Yue; Mayr, Doris; Schmoeckel, Elisa; Sattler, Cornelia; Kolben, Thomas; Hester, Anna; Fürst, Sophie; Burges, Alexander; Mahner, Sven; Jeschke, Udo; Trillsch, Fabian

doi:10.1007/s00418-020-01894-6

Cited by 18 publications

(22 citation statements)

References 49 publications

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“…However, THR has been identified to show cancer-promoting activities during BC development [24]. In the case of VDR, a direct link between the cytoplasmic localization of VDR and impaired OS in ovarian cancer has been reported [25]. Furthermore, higher cytoplasmic VDR expression in colon and vulvar cancer, as well as in malignant melanoma, had an impact on tumor progression and prognosis [66][67][68].…”

Section: Discussionmentioning

confidence: 99%

“…Studies on the role of NR in distinct intracellular compartments indicate a specific prognostic value, depending on the subcellular localization [24]. Czogalla et al demonstrated a direct link between the cytoplasmic localization of VDR and impaired overall survival (OS) in ovarian cancer [25]. In the case of THR, high nuclear localization was reported to be a positive predictive factor for OS in epithelial ovarian cancer [22].…”

Section: Introductionmentioning

confidence: 99%

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Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer

Zehni

Batz

Cavaillès

et al. 2021

Cancers

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The aim of this retrospective study was to assess the prognostic value of cytoplasmic versus nuclear RXRα expression in breast cancer (BC) tissue samples and to correlate the results with clinicopathological parameters. In 319 BC patients, the expression of RXRα was evaluated via immunohistochemistry. Prognosis-determining aspects were calculated through uni- and multivariate analyses. Correlation analysis revealed a trend association with nuclear RXRα expression regarding an improved overall survival (OS) (p = 0.078), whereas cytoplasmic RXRα expression was significantly correlated with a poor outcomes in terms of both OS (p = 0.038) and disease-free survival (DFS) (p = 0.037). Strengthening these results, cytoplasmic RXRα was found to be an independent marker for DFS (p = 0.023), when adjusted to clinicopathological parameters, whereas nuclear RXRα expression was positively associated with lower TNM-staging, i.e., pT (p = 0.01), pN (p = 0.029) and pM (p = 0.001). Additionally, cytoplasmic RXRα expression was positively associated with a higher histopathological tumor grading (p = 0.02). Cytoplasmic RXRα was also found to be a negative prognosticator for Her-2neu-negative and triple-negative patients. Altogether, these findings support the hypothesis that the subcellular localization of RXRα plays an important role in carcinogenesis and the prognosis of BC. The expression of cytoplasmic RXRα is correlated with a more aggressive course of the disease, whereas nuclear RXRα expression appears to be a protective factor. These data may help to identify high-risk BC subgroups in order to find possible specific options in targeted tumor therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytoplasmic Localization of RXRα Determines Outcome in Breast Cancer

Zehni

Batz

Cavaillès

et al. 2021

Cancers

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“…LXR [ 283 – 285 ], PXR [ 286 ], VDR [ 287 – 296 ] or CAR [ 297 , 298 ] activation was shown to exert protective features against ovarian cancer, similar to BA-elicited effects suggesting that BAs may have a more profound role in protecting against ovarian cancer. These protective effects involved the suppression of proliferation [ 283 , 284 , 286 ], invasion [ 291 ], EMT [ 288 ], de novo fatty acid biosynthesis [ 295 ], the proportions of the cancer stem cell population [ 289 ], and the improvement of the efficacy of chemotherapy [ 285 , 297 , 298 ] culminating in better patient survival [ 292 , 293 ].…”

Section: Effects Of Bile Acids In Cancersmentioning

confidence: 99%

The role of bile acids in carcinogenesis

Režen

Rozman

Kovàcs

et al. 2022

Cell. Mol. Life Sci.

144

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Bile acids are soluble derivatives of cholesterol produced in the liver that subsequently undergo bacterial transformation yielding a diverse array of metabolites. The bulk of bile acid synthesis takes place in the liver yielding primary bile acids; however, other tissues have also the capacity to generate bile acids (e.g. ovaries). Hepatic bile acids are then transported to bile and are subsequently released into the intestines. In the large intestine, a fraction of primary bile acids is converted to secondary bile acids by gut bacteria. The majority of the intestinal bile acids undergo reuptake and return to the liver. A small fraction of secondary and primary bile acids remains in the circulation and exert receptor-mediated and pure chemical effects (e.g. acidic bile in oesophageal cancer) on cancer cells. In this review, we assess how changes to bile acid biosynthesis, bile acid flux and local bile acid concentration modulate the behavior of different cancers. Here, we present in-depth the involvement of bile acids in oesophageal, gastric, hepatocellular, pancreatic, colorectal, breast, prostate, ovarian cancer. Previous studies often used bile acids in supraphysiological concentration, sometimes in concentrations 1000 times higher than the highest reported tissue or serum concentrations likely eliciting unspecific effects, a practice that we advocate against in this review. Furthermore, we show that, although bile acids were classically considered as pro-carcinogenic agents (e.g. oesophageal cancer), the dogma that switch, as lower concentrations of bile acids that correspond to their serum or tissue reference concentration possess anticancer activity in a subset of cancers. Differences in the response of cancers to bile acids lie in the differential expression of bile acid receptors between cancers (e.g. FXR vs. TGR5). UDCA, a bile acid that is sold as a generic medication against cholestasis or biliary surge, and its conjugates were identified with almost purely anticancer features suggesting a possibility for drug repurposing. Taken together, bile acids were considered as tumor inducers or tumor promoter molecules; nevertheless, in certain cancers, like breast cancer, bile acids in their reference concentrations may act as tumor suppressors suggesting a Janus-faced nature of bile acids in carcinogenesis.

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“…(5) clear cell histology. Given the heterogeneity of ovarian cancer subtypes, Czogalla et al (2020) have performed an immunohistochemical analysis of VDR in these subtypes, with the aim of correlating expression with patient survival. VDR immunoreactivity was detected in both the nucleus and cytoplasm as expected.…”

Section: Vitamin D Receptor (Vdr) Expression As a Potential Prognostic Marker For Ovarian Cancermentioning

confidence: 99%

“…CI confidence interval, FIGO Fédération Internationale de Gynécologie et d'Obstétrique stage. From Czogalla et al (2020)…”

Section: Vitamin D Receptor (Vdr) Expression As a Potential Prognostic Marker For Ovarian Cancerunclassified