Expression of thioredoxin 1 and peroxiredoxins in squamous cervical carcinoma and its predictive role in NACT

BMC Cancer. 2019 Aug 30;19(1):865. doi: 10.1186/s12885-019-6046-x.

Abstract

Background: This study aims to investigate the expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 in bulky cervical squamous carcinoma and its predictive role in cisplatin-based neoadjuvant chemotherapy.

Methods: Initially, the expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 protein was analyzed in 13 human cervical squamous cancer tissues and their paired adjacent non-cancerous tissues by western-blotting and immunohistochemistry. Then, correlation between the expression of thioredoxin 1, peroxiredoxin 1, peroxiredoxin 2 and responses to cisplatin-based neoadjuvant chemotherapy was analyzed in 35 paired tumor samples (pre- and post-chemotherapy) from bulky cervical squamous cancer patients by immunohistochemistry.

Results: A clinical response occurred in 48.6% (17/35) of patients, including 14.3% (5/35) with a complete response and 34.3% (12/35) with a partial response. The expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 was much higher in cervical squamous cancer tissues compared with paired adjacent non-cancerous tissues by western-blotting and immunohistochemistry. Additionally, the expression of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 was significantly up-regulated in post-chemotherapy tissues compared to pre-chemotherapy cervical cancer tissues. High levels of thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 were associated with a poor chemotherapy response in cervical squamous cancer patients.

Conclusions: Thioredoxin 1, peroxiredoxin 1 and peroxiredoxin 2 are frequently over-expressed in cervical squamous cancer. High expression levels of these proteins were related to a poor response to cisplatin-based neoadjuvant chemotherapy. The present study is the first report that thioredoxin peroxidase system may serve as a prediction of the responses to neoadjuvant chemotherapy in cervical squamous cancer.

Keywords: Cervical squamous cancer; Neoadjuvant chemotherapy; Peroxiredoxin 1; Peroxiredoxin 2; Thioredoxin 1.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Case-Control Studies
  • Cisplatin / therapeutic use*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Peroxiredoxins / metabolism*
  • Prognosis
  • Survival Analysis
  • Thioredoxins / metabolism*
  • Treatment Outcome
  • Up-Regulation
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / metabolism

Substances

  • Antineoplastic Agents
  • TXN protein, human
  • Thioredoxins
  • PRDX1 protein, human
  • PRDX2 protein, human
  • Peroxiredoxins
  • Cisplatin