Expression of CDKN1A/p21 and TGFBR2 in breast cancer and their prognostic significance

Int J Clin Exp Pathol. 2015 Nov 1;8(11):14619-29. eCollection 2015.

Abstract

Background: A new diagnostic and prognostic biomarker may be of value in cancer diseases. Our study aimed to evaluate the CDKN1A/p21 and TGFBR2 level measurable in a cohort of patients with breast cancer after mastectomy, and to confirm their suitability to serve as prognostic biomarkers of the cancer.

Methods: The expression levels of CDKN1A/p21 and TGFBR2 were detected by reverse transcription-PCR (RT-PCR), western blot assay and immunohistochemical staining for 65 primary tumor samples and paired adjacent noncancerous breast tissues. Their relations to clinicopathologic parameters and to the prognosis of patients with breast cancer were analyzed.

Results: We found the mRNA and protein expression levels of CDKN1A/p21 were significantly upregulated in breast cancer tissues compared with adjacent nontumorous breast tissues. Increased CDKN1A/p21 expression showed a significant correlation with larger tumor size (P=0.014), higher tumor dedifferentiation grade (P=0.021), lymph node metastasis (P=0.019) and a shorter disease-free survival (P=0.044). Contrarily, the expression levels of TGFBR2 mRNA and protein were significantly decreased in breast cancer tissues compared with adjacent nontumorous breast tissues. Underexpression of TGFBR2 in breast cancer was correlated with larger tumor size (P=0.034), lymph node metastasis (P=0.039) and a shorter disease-free survival (P=0.035). Statistical analysis suggested that there was no significant association between CDKN1A/p21 and TGFBR2 expression.

Conclusions: in summary, our results suggested that high CDKN1A/p21 and low TGFBR2 expression was closely correlated with adverse pathological parameters and poor prognosis in breast cancer. Both CDKN1A/p21 and TGFBR2 are presented as possible candidates for breast cancer biomarkers.

Keywords: CDKN1A/p21; TGFBR2; biomarker; breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Blotting, Western
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cyclin-Dependent Kinase Inhibitor p21 / analysis
  • Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Protein Serine-Threonine Kinases / analysis
  • Protein Serine-Threonine Kinases / biosynthesis*
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / analysis
  • Receptors, Transforming Growth Factor beta / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Receptors, Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II