Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer
Molecular biomarkers that can predict survival and therapeutic outcome are still lacking for cervical cancer. Here we measured a panel of 19 serum proteins in sera from 565 patients with stage II or III cervical cancer and identified 10 proteins that have an impact on disease specific survival (DSS)...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/10/2899 |
| _version_ | 1797551435258265600 |
|---|---|
| author | Sharad Purohit Wenbo Zhi Daron G. Ferris Manual Alverez Lynn Kim Hoang Tran Paul Minh Huy Tran Boying Dun Diane Hopkins Bruno dos Santos Sharad Ghamande Jin-Xiong She |
| author_facet | Sharad Purohit Wenbo Zhi Daron G. Ferris Manual Alverez Lynn Kim Hoang Tran Paul Minh Huy Tran Boying Dun Diane Hopkins Bruno dos Santos Sharad Ghamande Jin-Xiong She |
| author_sort | Sharad Purohit |
| collection | DOAJ |
| description | Molecular biomarkers that can predict survival and therapeutic outcome are still lacking for cervical cancer. Here we measured a panel of 19 serum proteins in sera from 565 patients with stage II or III cervical cancer and identified 10 proteins that have an impact on disease specific survival (DSS) (Hazzard’s ratio; HR = 1.51–2.1). Surprisingly, all ten proteins are implicated in senescence-associated secreted phenotype (SASP), a hallmark of cellular senescence. Machine learning using Ridge regression of these SASP proteins can robustly stratify patients with high SASP, which is associated with poor survival, and patients with low SASP associated with good survival (HR = 3.09–4.52). Furthermore, brachytherapy, an effective therapy for cervical cancer, greatly improves survival in SASP-high patients (HR = 3.3, <i>p</i> < 5 × 10<sup>−5</sup>) but has little impact on survival of SASP-low patients (HR = 1.5, <i>p</i> = 0.31). These results demonstrate that cellular senescence is a major determining factor for survival and therapeutic response in cervical cancer and suggest that senescence reduction therapy may be an efficacious strategy to improve the therapeutic outcome of cervical cancer. |
| first_indexed | 2024-03-10T15:46:03Z |
| format | Article |
| id | doaj.art-bce97835c01147099325d1d5a34a420c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:46:03Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bce97835c01147099325d1d5a34a420c2023-11-20T16:29:56ZengMDPI AGCancers2072-66942020-10-011210289910.3390/cancers12102899Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical CancerSharad Purohit0Wenbo Zhi1Daron G. Ferris2Manual Alverez3Lynn Kim Hoang Tran4Paul Minh Huy Tran5Boying Dun6Diane Hopkins7Bruno dos Santos8Sharad Ghamande9Jin-Xiong She10Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USADepartment of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USADepartment of Gynecologic Oncology, Instituto Nacional de Enfermedades Neoplasicas, Surquillo, Lima 15038, PeruCenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USAJinfiniti Precision Medicine, Inc., Augusta, GA 30912, USADepartment of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USACenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USAMolecular biomarkers that can predict survival and therapeutic outcome are still lacking for cervical cancer. Here we measured a panel of 19 serum proteins in sera from 565 patients with stage II or III cervical cancer and identified 10 proteins that have an impact on disease specific survival (DSS) (Hazzard’s ratio; HR = 1.51–2.1). Surprisingly, all ten proteins are implicated in senescence-associated secreted phenotype (SASP), a hallmark of cellular senescence. Machine learning using Ridge regression of these SASP proteins can robustly stratify patients with high SASP, which is associated with poor survival, and patients with low SASP associated with good survival (HR = 3.09–4.52). Furthermore, brachytherapy, an effective therapy for cervical cancer, greatly improves survival in SASP-high patients (HR = 3.3, <i>p</i> < 5 × 10<sup>−5</sup>) but has little impact on survival of SASP-low patients (HR = 1.5, <i>p</i> = 0.31). These results demonstrate that cellular senescence is a major determining factor for survival and therapeutic response in cervical cancer and suggest that senescence reduction therapy may be an efficacious strategy to improve the therapeutic outcome of cervical cancer.https://www.mdpi.com/2072-6694/12/10/2899gynecologic cancerscervical neoplasiaserum proteinsproteomicsbiomarkersradiation therapy |
| spellingShingle | Sharad Purohit Wenbo Zhi Daron G. Ferris Manual Alverez Lynn Kim Hoang Tran Paul Minh Huy Tran Boying Dun Diane Hopkins Bruno dos Santos Sharad Ghamande Jin-Xiong She Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer Cancers gynecologic cancers cervical neoplasia serum proteins proteomics biomarkers radiation therapy |
| title | Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer |
| title_full | Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer |
| title_fullStr | Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer |
| title_full_unstemmed | Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer |
| title_short | Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer |
| title_sort | senescence associated secretory phenotype determines survival and therapeutic response in cervical cancer |
| topic | gynecologic cancers cervical neoplasia serum proteins proteomics biomarkers radiation therapy |
| url | https://www.mdpi.com/2072-6694/12/10/2899 |
| work_keys_str_mv | AT sharadpurohit senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT wenbozhi senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT darongferris senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT manualalverez senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT lynnkimhoangtran senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT paulminhhuytran senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT boyingdun senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT dianehopkins senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT brunodossantos senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT sharadghamande senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer AT jinxiongshe senescenceassociatedsecretoryphenotypedeterminessurvivalandtherapeuticresponseincervicalcancer |