Role of Smac, survivin, XIAP, and Omi/HtrA2 proteins in determining the chemotherapeutic response of patients with cervical cancer treated with neoadjuvant chemotherapy

Cancer Biomark. 2019;26(3):249-259. doi: 10.3233/CBM-182165.

Abstract

Neoadjuvant chemotherapy (NACT) followed by radical surgical hysterectomy and pelvic lymph node dissection is considered an effective method to treat patients with bulky stage IB-IIA cervical cancer, but not all patients benefit from NACT. Apoptotic proteins play important roles in the progression of chemotherapy, and second mitochondria-derived activator of caspase (Smac) may have a cooperative relationship with Omi/HtrA2, leading to carcinogenesis and chemotherapy resistance. Chemosensitivity is an important prognostic factor for cervical cancer patients. The aim of this study was to evaluate the significance of Smac, survivin, X-linked inhibitor-of-apoptosis protein (XIAP), and Omi/HtrA2 expression in predicting the response to neoadjuvant chemotherapy and the prognostic significance of te expression of these proteins in cervical cancer patients. Our findings showed that low expression levels of survivin and high expression levels of Omi/HtrA2 in chemotherapy-responsive cervical carcinoma patients significantly increased chemosensitivity.

Keywords: Cervical carcinoma; IHC; apoptotic proteins; chemosensitivity.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • Biomarkers, Tumor / metabolism*
  • Biopsy
  • Cervix Uteri / pathology*
  • Cervix Uteri / surgery
  • Drug Resistance, Neoplasm
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • High-Temperature Requirement A Serine Peptidase 2 / metabolism
  • Humans
  • Hysterectomy
  • Lymph Node Excision
  • Mitochondrial Proteins / metabolism
  • Neoadjuvant Therapy / methods*
  • Prognosis
  • Progression-Free Survival
  • Response Evaluation Criteria in Solid Tumors
  • Survival Rate
  • Survivin / metabolism
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology
  • X-Linked Inhibitor of Apoptosis Protein / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BIRC5 protein, human
  • Biomarkers, Tumor
  • DIABLO protein, human
  • Mitochondrial Proteins
  • Survivin
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • HTRA2 protein, human
  • High-Temperature Requirement A Serine Peptidase 2