Caspase14 expression is associated with triple negative phenotypes and cancer stem cell marker expression in breast cancer patients

J Surg Oncol. 2017 Nov;116(6):706-715. doi: 10.1002/jso.24705. Epub 2017 Jun 1.

Abstract

Background and objectives: The Caspase14 (CASP14) was reported that the low expression of CASP14 in ovarian cancer and colon cancer was associated with cancer progression, on the other hand, that the CASP14 expression in breast cancer was higher than that of non-cancerous tissues. The purpose of this study is to determine the clinical significance of CASP14 in breast cancer.

Methods: We performed immunohistochemistry for CASP14, ER, PgR, HER2, Ki67, EGFR, CK5/6, CD44, CD24, ALDH1, claudins, and androgen receptor in 222 breast cancer patients including 55 TNBC cases, and evaluated the relationship of CASP14, above-mentioned markers, and prognosis. Using public microarray database of breast cancer, the prognostic value of CASP14 was calculated.

Results: High CASP14 expression was significantly associated with TNBC subtype (P = 0.015), nuclear grade (P = 0.006), Ki67, EGFR (P < 0.001, P = 0.016), ALDH1, CD44 and CD24 (P < 0.001, P < 0.001, P = 0.001) in 222 breast cancer cases, and the high expression of claudin1 (P = 0.017), and androgen receptor (P = 0.002) in TNBC cases was related to the high CASP14. According to the public database, survival in the high CASP14 breast cancer patients was shorter than low CASP14 patients.

Conclusions: High CASP14 expression is a marker of breast cancer aggressiveness in association with proliferation, TNBC phenotype, and cancer stemness.

Keywords: CASP14; luminal androgen receptor; stem cell marker; therapeutic target; triple negative breast cancer.

MeSH terms

  • Caspases / biosynthesis*
  • Caspases / genetics
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunohistochemistry
  • MCF-7 Cells
  • Middle Aged
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Phenotype
  • Triple Negative Breast Neoplasms / enzymology*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • CASP14 protein, human
  • Caspases