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Analysis of the hippo transducers TAZ and YAP in cervical cancer and its microenvironment

Authors :
Buglioni, Simonetta
Vici, Patrizia
Sergi, Domenico
Pizzuti, Laura
Di Lauro, Luigi
Antoniani, Barbara
Sperati, Francesca
Terrenato, Irene
Carosi, Mariantonia
Gamucci, Teresa
Vincenzoni, Cristina
Mariani, Luciano
Vizza, Enrico
Venuti, Aldo
Sanguineti, Giuseppe
Gadducci, Angiolo
Barba, Maddalena
Natoli, Clara
Vitale, Ilio
Mottolese, Marcella
De Maria Marchiano, Ruggero
Maugeri-Saccà, Marcello
De Maria Marchiano, Ruggero (ORCID:0000-0003-2255-0583)
Buglioni, Simonetta
Vici, Patrizia
Sergi, Domenico
Pizzuti, Laura
Di Lauro, Luigi
Antoniani, Barbara
Sperati, Francesca
Terrenato, Irene
Carosi, Mariantonia
Gamucci, Teresa
Vincenzoni, Cristina
Mariani, Luciano
Vizza, Enrico
Venuti, Aldo
Sanguineti, Giuseppe
Gadducci, Angiolo
Barba, Maddalena
Natoli, Clara
Vitale, Ilio
Mottolese, Marcella
De Maria Marchiano, Ruggero
Maugeri-Saccà, Marcello
De Maria Marchiano, Ruggero (ORCID:0000-0003-2255-0583)
Publication Year :
2016

Abstract

Hippo is a tumor-suppressor pathway that negatively regulates the oncoproteins TAZ and YAP. Moreover, Hippo affects the biology of a variety of non-neoplastic cells in the tumor microenvironment, even including immune cells. We herein assessed the predictive role of TAZ and YAP, assessed by immunohistochemistry, in 50 cervical cancer patients prevalently treated with neoadjuvant chemotherapy. Tumors were classified as positive or negative according to the percentage of tumor-expressing cells and cellular localization. TAZ/YAP were also evaluated in non-neoplastic cells, namely endothelial cells, non-lymphocytic stromal cells and tumor-infiltrating lymphocytes (TILs). TAZ expression in cancer cells (TAZpos) was associated with a reduced pathological complete response (pCR) rate (p = 0.041). Conversely, the expression of TAZ and YAP in TILs (TAZTIL+and YAPTIL+) seemed to be associated with increased pCRs (p = 0.083 and p = 0.018, respectively). When testing the predictive significance of the concomitant expression of TAZ in cancer cells and its absence in TILs (TAZpos/TAZTIL-), patients with TAZpos/TAZTIL-showed lower pCR rate (p = 0.001), as confirmed in multivariate analysis (TAZpos/TAZTIL-: OR 8.67, 95% CI: 2.31–32.52, p = 0.001). Sensitivity analysis carried out in the 41 patients treated with neoadjuvant chemotherapy yielded comparable results (TAZpos/TAZTIL-: OR 11.0, 95% CI: 2.42–49.91, p = 0.002). Internal validation carried out with two different procedures confirmed the robustness of this model. Overall, we found evidence on the association between TAZ expression in cervical cancer cells and reduced pCR rate. Conversely, the expression of the Hippo transducers in TILs may predict increased treatment efficacy, possibly mirroring the activation of a non-canonical Hippo/MST pathway necessary for T-cells activation and survival.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1105032159
Document Type :
Electronic Resource