title: Identification of protein biomarkers and signaling pathways associated with prostate cancer radioresistance using label-free LC-MS/MS proteomic approach.
abstract: Identifying biomarkers and signaling pathways are important for the management of prostate cancer (CaP) radioresistance. In this study, we identified differential proteins and signaling pathways from parental CaP cell lines and CaP radioresistant (RR) sublines using a label-free LC-MS/MS proteomics approach. A total of 309 signaling pathway proteins were identified to be significantly altered between CaP and CaP-RR cells (p ≤ 0.05, fold differences >1.5, ≥80% power). Among these proteins, nineteen are common among three paired CaP cell lines and associated with metastasis, progression and radioresistance. The PI3K/Akt, VEGF and glucose metabolism pathways were identified as the main pathways associated with CaP radioresistance. In addition, the identified potential protein markers were further validated in CaP-RR cell lines and subcutaneous (s.c) animal xenografts by western blotting and immunohistochemistry, respectively and protein aldolase A (ALDOA) was selected for a radiosensitivity study. We found the depletion of ALDOA combined with radiotherapy effectively reduced colony formation, induced more apoptosis and increased radiosensitivity in CaP-RR cells. Our findings indicate that CaP radioresistance is caused by multifactorial traits and downregulation of ALDOA increases radiosensitivity in CaP-RR cells, suggesting that controlling these identified proteins or signaling pathways in combination with radiotherapy may hold promise to overcome CaP radioresistance.
authors.affiliation: Cancer Care Centre, St George Hospital, Kogarah, NSW 2217, Australia.|St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Kensington, NSW 2052, Australia.|Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chang
authors.affiliation: Cancer Care Centre, St George Hospital, Kogarah, NSW 2217, Australia.|St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Kensington, NSW 2052, Australia.
authors.forename: Jie
authors.initials: J
authors.lastname: Ni
authors.affiliation: Cancer Care Centre, St George Hospital, Kogarah, NSW 2217, Australia.|St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Kensington, NSW 2052, Australia.|SEALS, Anatomical Pathology, St George Hospital, Kogarah, NSW 2217, Australia.
authors.forename: Julia
authors.initials: J
authors.lastname: Beretov
authors.affiliation: Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, UNSW, Kensington, NSW 2052, Australia.|School of Medical Science, UNSW, Kensington, NSW 2052, Australia.
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Wasinger
authors.affiliation: Cancer Care Centre, St George Hospital, Kogarah, NSW 2217, Australia.|St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Kensington, NSW 2052, Australia.
authors.forename: Jingli
authors.initials: J
authors.lastname: Hao
authors.affiliation: Cancer Care Centre, St George Hospital, Kogarah, NSW 2217, Australia.|St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Kensington, NSW 2052, Australia.
authors.forename: Joseph
authors.initials: J
authors.lastname: Bucci
authors.affiliation: Department of Urology, St George Hospital, Kogarah, NSW 2217, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Malouf
authors.affiliation: Department of Urology, St George Hospital, Kogarah, NSW 2217, Australia.|Australian School of Advanced Medicine, Macquarie University, NSW 2109, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Gillatt
authors.affiliation: Cancer Care Centre, St George Hospital, Kogarah, NSW 2217, Australia.|St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Kensington, NSW 2052, Australia.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Graham
authors.affiliation: Cancer Care Centre, St George Hospital, Kogarah, NSW 2217, Australia.|St George and Sutherland Clinical School, Faculty of Medicine, UNSW, Kensington, NSW 2052, Australia.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D015415:Biomarkers; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy; D020543:Proteome; D040901:Proteomics / Q000379:methods; D011836:Radiation Tolerance / Q000235:genetics; D015203:Reproducibility of Results; D015398:Signal Transduction; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D020543:Proteome