Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma
Background: The possible involvement of p53 signaling, FGFR3 expression, and <i>FGFR3</i> mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main aim of our study was to explore predictive value of p53 expression, FGFR3 expression, and...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| author | Ekaterina Blinova Elena Samishina Olga Deryabina Dmitry Blinov Dmitry Roshchin Evgeniia Shich Oxana Tumutolova Ilya Fedoseykin Anna Epishkina Haydar Barakat Andrey Kaprin Kirill Zhandarov Dmitrij Perepechin Dmitrij Merinov Gordey Brykin Karen Arutiunian Stanislav Serebrianyi Artem Mirontsev Andrew Kozdoba |
| author_facet | Ekaterina Blinova Elena Samishina Olga Deryabina Dmitry Blinov Dmitry Roshchin Evgeniia Shich Oxana Tumutolova Ilya Fedoseykin Anna Epishkina Haydar Barakat Andrey Kaprin Kirill Zhandarov Dmitrij Perepechin Dmitrij Merinov Gordey Brykin Karen Arutiunian Stanislav Serebrianyi Artem Mirontsev Andrew Kozdoba |
| author_sort | Ekaterina Blinova |
| collection | DOAJ |
| description | Background: The possible involvement of p53 signaling, FGFR3 expression, and <i>FGFR3</i> mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main aim of our study was to explore predictive value of p53 expression, FGFR3 expression, and its gene mutation status for the therapeutic success of anti-PD-L1 treatment in the patient-derived murine model of recurrent high-PD-L1(+) GATA3(−)/CR5/6(−) high-grade and low-grade NMIBC. Methods: twenty lines of patient-derived xenografts (PDXs) of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones—low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals’ survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The FGFR3 expression and <i>FGFR3</i> mutations in codons 248 and 249 were detected by real-time polymerase chain reaction. Results: The expression of p53 protein is an independent factor affecting the animals’ survival time [HR = 0.036, <i>p</i> = 0.031] of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative NMIBC PDX. The FGFR3 expression and <i>FGFR3</i> mutation rate have no impact on the anti-PD-L1 treatment response in the interventional groups. Conclusions: p53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(−)/CR5/6(−)-relapsed noninvasive bladder cancer. |
| first_indexed | 2024-03-10T07:35:31Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:35:31Z |
| publishDate | 2021-09-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-287dc68fa166405ea247c9153103b21c2023-11-22T13:28:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218985610.3390/ijms22189856Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial CarcinomaEkaterina Blinova0Elena Samishina1Olga Deryabina2Dmitry Blinov3Dmitry Roshchin4Evgeniia Shich5Oxana Tumutolova6Ilya Fedoseykin7Anna Epishkina8Haydar Barakat9Andrey Kaprin10Kirill Zhandarov11Dmitrij Perepechin12Dmitrij Merinov13Gordey Brykin14Karen Arutiunian15Stanislav Serebrianyi16Artem Mirontsev17Andrew Kozdoba18Department of Clinical Anatomy and Operative Surgery, Department of Pharmacology and Pharmaceutic Technology, Sechenov University, 8/1 Trubetzkaya Street, 119991 Moscow, RussiaLaboratory of Molecular Pharmacology and Drug Design, Department of Pharmaceutical Chemistry, All-Union Research Center for Biological Active Compounds Safety, 23 Kirova Street, 142450 Staraja Kupavna, RussiaLaboratory of Pharmacology, Department of Pathology, National Research Ogarev Mordovia State University, 68 Bolshevistskaya Street, 430005 Saransk, RussiaLaboratory of Molecular Pharmacology and Drug Design, Department of Pharmaceutical Chemistry, All-Union Research Center for Biological Active Compounds Safety, 23 Kirova Street, 142450 Staraja Kupavna, RussiaDepartment of Oncological Urology, Russian National Research Medical Center of Radiology, Botkinsky Proezd, 125284 Moscow, RussiaDepartment of Clinical Anatomy and Operative Surgery, Department of Pharmacology and Pharmaceutic Technology, Sechenov University, 8/1 Trubetzkaya Street, 119991 Moscow, RussiaLaboratory of Pharmacology, Department of Pathology, National Research Ogarev Mordovia State University, 68 Bolshevistskaya Street, 430005 Saransk, RussiaDepartment of Clinical Anatomy and Operative Surgery, Department of Pharmacology and Pharmaceutic Technology, Sechenov University, 8/1 Trubetzkaya Street, 119991 Moscow, RussiaDepartment of Clinical Anatomy and Operative Surgery, Department of Pharmacology and Pharmaceutic Technology, Sechenov University, 8/1 Trubetzkaya Street, 119991 Moscow, RussiaDepartment of Propaedeutic of Dental Diseases, People’s Friendship University of Russia, 6 Miklukho-Maklaya Street, 117198 Moscow, RussiaDepartment of Oncological Urology, Russian National Research Medical Center of Radiology, Botkinsky Proezd, 125284 Moscow, RussiaDepartment of Clinical Anatomy and Operative Surgery, Department of Pharmacology and Pharmaceutic Technology, Sechenov University, 8/1 Trubetzkaya Street, 119991 Moscow, RussiaDepartment of Oncological Urology, Russian National Research Medical Center of Radiology, Botkinsky Proezd, 125284 Moscow, RussiaDepartment of Oncological Urology, Russian National Research Medical Center of Radiology, Botkinsky Proezd, 125284 Moscow, RussiaDepartment of Clinical Anatomy and Operative Surgery, Department of Pharmacology and Pharmaceutic Technology, Sechenov University, 8/1 Trubetzkaya Street, 119991 Moscow, RussiaDepartment of Urology, Andrology and Oncology, Pirogov Russian National Research Medical University, 1 Ostrovityanova Street, 117997 Moscow, RussiaDepartment of Oncological Urology, Russian National Research Medical Center of Radiology, Botkinsky Proezd, 125284 Moscow, RussiaDepartment of Clinical Anatomy and Operative Surgery, Department of Pharmacology and Pharmaceutic Technology, Sechenov University, 8/1 Trubetzkaya Street, 119991 Moscow, RussiaDepartment of Urology, Andrology and Oncology, Pirogov Russian National Research Medical University, 1 Ostrovityanova Street, 117997 Moscow, RussiaBackground: The possible involvement of p53 signaling, FGFR3 expression, and <i>FGFR3</i> mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main aim of our study was to explore predictive value of p53 expression, FGFR3 expression, and its gene mutation status for the therapeutic success of anti-PD-L1 treatment in the patient-derived murine model of recurrent high-PD-L1(+) GATA3(−)/CR5/6(−) high-grade and low-grade NMIBC. Methods: twenty lines of patient-derived xenografts (PDXs) of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones—low-grade bladder cancer. Acceptors of each grade-related branch received specific anti-PD-L1 antibodies. Animals’ survival, tumor-doubling time, and remote metastasis were followed during the post-interventional period. PD-L1, GATA3, CR5/6, and p53 protein expressions in engrafted tumors were assessed by immunohistochemistry. The FGFR3 expression and <i>FGFR3</i> mutations in codons 248 and 249 were detected by real-time polymerase chain reaction. Results: The expression of p53 protein is an independent factor affecting the animals’ survival time [HR = 0.036, <i>p</i> = 0.031] of anti-PD-L1-treated mice with low-grade high-PD-L1(+) double-negative NMIBC PDX. The FGFR3 expression and <i>FGFR3</i> mutation rate have no impact on the anti-PD-L1 treatment response in the interventional groups. Conclusions: p53 expression may be considered as a prognostic factor for the anti-PD-L1 treatment efficacy of low-grade high-PD-L1-positive GATA3(−)/CR5/6(−)-relapsed noninvasive bladder cancer.https://www.mdpi.com/1422-0067/22/18/9856nonmuscular invasive bladder cancerp53 expressiondouble-negative molecular subtype<i>FGFR3</i> mutationsFGFR3 expressionanti-PD-L1 therapy |
| spellingShingle | Ekaterina Blinova Elena Samishina Olga Deryabina Dmitry Blinov Dmitry Roshchin Evgeniia Shich Oxana Tumutolova Ilya Fedoseykin Anna Epishkina Haydar Barakat Andrey Kaprin Kirill Zhandarov Dmitrij Perepechin Dmitrij Merinov Gordey Brykin Karen Arutiunian Stanislav Serebrianyi Artem Mirontsev Andrew Kozdoba Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma International Journal of Molecular Sciences nonmuscular invasive bladder cancer p53 expression double-negative molecular subtype <i>FGFR3</i> mutations FGFR3 expression anti-PD-L1 therapy |
| title | Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma |
| title_full | Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma |
| title_fullStr | Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma |
| title_full_unstemmed | Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma |
| title_short | Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma |
| title_sort | expression of p53 protein associates with anti pd l1 treatment response on human derived xenograft model of gata3 cr5 6 negative recurrent nonmuscular invasive bladder urothelial carcinoma |
| topic | nonmuscular invasive bladder cancer p53 expression double-negative molecular subtype <i>FGFR3</i> mutations FGFR3 expression anti-PD-L1 therapy |
| url | https://www.mdpi.com/1422-0067/22/18/9856 |
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