Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer

Cancers

Diane Hopkins¹  Boying Dun¹  Jin-Xiong She¹  LynnKim Hoang Tran¹  PaulMinh Huy Tran¹  Sharad Purohit¹  Wenbo Zhi¹  Manual Alverez²  DaronG. Ferris³  Sharad Ghamande³  Brunodos Santos⁴ 

[1] Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USA;Department of Gynecologic Oncology, Instituto Nacional de Enfermedades Neoplasicas, Surquillo, Lima 15038, Peru;Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, 1120, 15th St, Augusta, GA 30912, USA;Jinfiniti Precision Medicine, Inc., Augusta, GA 30912, USA;

关键词: gynecologic cancers;    cervical neoplasia;    serum proteins;    proteomics;    biomarkers;    radiation therapy;   

DOI  :  10.3390/cancers12102899

来源: DOAJ

【 摘 要 】

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, p < 5 × 10⁻⁵) but has little impact on survival of SASP-low patients (HR = 1.5, p = 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.

【 授权许可】

Unknown