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Article

LDOC1 as Negative Prognostic Marker for Vulvar Cancer Patients

1
Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany
2
Department of Pathology, LMU Munich, Thalkirchner Str. 142, 80337 Munich, Germany
3
Department of Obstetrics, Klinik Hallerwiese, Sankt-Johannis-Mühlgasse 19, 90419 Nürnberg, Germany
4
Department of Gynecology and Gynecologic Oncology, Charité University, Charitéplatz 1, 10117 Berlin, Germany
5
Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglin Street 2, 86156 Augsburg, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9287; https://doi.org/10.3390/ijms21239287
Received: 15 October 2020 / Revised: 2 December 2020 / Accepted: 3 December 2020 / Published: 5 December 2020
So far, studies about targeted therapies and predictive biomarkers for vulva carcinomas are rare. The leucine zipper downregulated in cancer 1 gene (LDOC1) has been identified in various carcinomas as a tumor-relevant protein influencing patients’ survival and prognosis. Due to the lack of information about LDOC1 and its exact functionality, this study focuses on the expression of LDOC1 in vulvar carcinoma cells and its surrounding immune cells as well as its correlation to clinicopathological characteristics and prognosis. Additionally, a possible regulation of LDOC1 in vulvar cancer cell lines via the NF-κB signaling pathway was analyzed. Vulvar carcinoma sections of 157 patients were immunohistochemically stained and examined regarding LDOC1 expression by using the immunoreactive score (IRS). To characterize LDOC1-positively stained immune cell subpopulations, immunofluorescence double staining was performed. The effect of the NF-κB inhibitor C-DIM 12 (3,3′-[(4-chlorophenyl)methylene]bis[1 H-indole]) on vulvar cancer cell lines A431 and SW 954 was measured according to MTT and BrdU assays. Baseline expression levels of LDOC1 in the vulvar cancer cell lines A431 and SW 954 was analyzed by real-time PCR. LDOC1 was expressed by about 90% of the cancer cells in the cytoplasm and about half of the cells in the nucleus. Cytoplasmatic expression of LDOC1 was associated with decreased ten-year overall survival of the patient, whereas nuclear staining showed a negative association with disease-free survival. Infiltrating immune cells were mainly macrophages followed by regulatory T cells. Incubation with C-DIM 12 decreased the cell viability and proliferation of vulvar cancer cell line A431, but not of cell line SW 954. LDOC1 expression on mRNA level was twice as high in the cell line A431 compared to the cell line SW 954. Overexpression of LDOC1 was associated with unfavorable overall and disease-free survival. Tumor growth could be inhibited by C-DIM 12 in vitro if the expressed LDOC1 level was high enough. View Full-Text
Keywords: vulvar carcinoma; LDOC1; cancer survival; prognosis; NF-κB; C-DIM 12 vulvar carcinoma; LDOC1; cancer survival; prognosis; NF-κB; C-DIM 12
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MDPI and ACS Style

Wanka, G.; Schmoeckel, E.; Mayr, D.; Fuerst, S.; Kuhn, C.; Mahner, S.; Knabl, J.; Karsten, M.M.; Dannecker, C.; Heidegger, H.H.; Vattai, A.; Jeschke, U.; Jueckstock, J. LDOC1 as Negative Prognostic Marker for Vulvar Cancer Patients. Int. J. Mol. Sci. 2020, 21, 9287. https://doi.org/10.3390/ijms21239287

AMA Style

Wanka G, Schmoeckel E, Mayr D, Fuerst S, Kuhn C, Mahner S, Knabl J, Karsten MM, Dannecker C, Heidegger HH, Vattai A, Jeschke U, Jueckstock J. LDOC1 as Negative Prognostic Marker for Vulvar Cancer Patients. International Journal of Molecular Sciences. 2020; 21(23):9287. https://doi.org/10.3390/ijms21239287

Chicago/Turabian Style

Wanka, Giulia; Schmoeckel, Elisa; Mayr, Doris; Fuerst, Sophie; Kuhn, Christina; Mahner, Sven; Knabl, Julia; Karsten, Maria M.; Dannecker, Christian; Heidegger, Helene H.; Vattai, Aurelia; Jeschke, Udo; Jueckstock, Julia. 2020. "LDOC1 as Negative Prognostic Marker for Vulvar Cancer Patients" Int. J. Mol. Sci. 21, no. 23: 9287. https://doi.org/10.3390/ijms21239287

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