Jang-Ming Su1, Ya-Ying Hsu2, Pinpin Lin3, Han Chang4. 1. Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C. College of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C. 2. Department of Pathology, College of Medicine, China Medical University, Taichung, Taiwan, R.O.C. 3. Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Taiwan, R.O.C. 4. Department of Pathology, College of Medicine, China Medical University, Taichung, Taiwan, R.O.C. Department of Pathology, China Medical University Hospital, Taichung, Taiwan, R.O.C. changhan@mail.cmu.edu.tw.
Abstract
BACKGROUND/AIM: Heat-shock protein 90 (HSP90) is a molecular chaperone that stabilizes many client proteins in normal and cancer cells, and approximately 3% of intracellular HSP90 is located in the nucleus. HSP90 is also targeted for the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to elucidate the clinical role of nuclear HSP90 levels in tissues from patients with NSCLC. MATERIALS AND METHODS: Nuclear and total HSP90 levels were assessed using immunohistochemistry. RESULTS: Multivariate logistic regression showed that the total HSP90 level was independently positively associated with age (p=0.041) and tumor histology of squamous type (p=0.007). By contrast, nuclear HSP90 level was independently positively associated with higher performance score (p=0.011), ever-smoking history (p=0.006) and presence of lymph node (p=0.036) or distant (p<0.001) metastasis, but not age or tumor histology. The level of nuclear HSP90, but not total HSP90, was negatively correlated with patient survival time (p<0.001). CONCLUSION: Nuclear accumulation of HSP90 might be a predictor of metastasis and survival in patients with NSCLC. Copyright
BACKGROUND/AIM: Heat-shock protein 90 (HSP90) is a molecular chaperone that stabilizes many client proteins in normal and cancer cells, and approximately 3% of intracellular HSP90 is located in the nucleus. HSP90 is also targeted for the treatment of advanced non-small cell lung cancer (NSCLC). This study aimed to elucidate the clinical role of nuclear HSP90 levels in tissues from patients with NSCLC. MATERIALS AND METHODS: Nuclear and total HSP90 levels were assessed using immunohistochemistry. RESULTS: Multivariate logistic regression showed that the total HSP90 level was independently positively associated with age (p=0.041) and tumor histology of squamous type (p=0.007). By contrast, nuclear HSP90 level was independently positively associated with higher performance score (p=0.011), ever-smoking history (p=0.006) and presence of lymph node (p=0.036) or distant (p<0.001) metastasis, but not age or tumor histology. The level of nuclear HSP90, but not total HSP90, was negatively correlated with patient survival time (p<0.001). CONCLUSION: Nuclear accumulation of HSP90 might be a predictor of metastasis and survival in patients with NSCLC. Copyright
Authors: Lucía Zhu; Diana Retana; Pedro García-Gómez; Laura Álvaro-Espinosa; Neibla Priego; Mariam Masmudi-Martín; Natalia Yebra; Lauritz Miarka; Elena Hernández-Encinas; Carmen Blanco-Aparicio; Sonia Martínez; Cecilia Sobrino; Nuria Ajenjo; Maria-Jesus Artiga; Eva Ortega-Paino; Raúl Torres-Ruiz; Sandra Rodríguez-Perales; Riccardo Soffietti; Luca Bertero; Paola Cassoni; Tobias Weiss; Javier Muñoz; Juan Manuel Sepúlveda; Pedro González-León; Luis Jiménez-Roldán; Luis Miguel Moreno; Olga Esteban; Ángel Pérez-Núñez; Aurelio Hernández-Laín; Oscar Toldos; Yolanda Ruano; Lucía Alcázar; Guillermo Blasco; José Fernández-Alén; Eduardo Caleiras; Miguel Lafarga; Diego Megías; Osvaldo Graña-Castro; Carolina Nör; Michael D Taylor; Leonie S Young; Damir Varešlija; Nicola Cosgrove; Fergus J Couch; Lorena Cussó; Manuel Desco; Silvana Mouron; Miguel Quintela-Fandino; Michael Weller; Joaquín Pastor; Manuel Valiente Journal: EMBO Mol Med Date: 2022-02-17 Impact factor: 12.137
Authors: Xiaoqian Li; Xuesong Tong; Bin Liu; Zeng Li; Jing Ding; Jiang Li; Min Zheng; Yuke Tian; Siyou Yan; Meiling Huang; Jun Ge Journal: J Int Med Res Date: 2021-12 Impact factor: 1.671