Can HE4 predict platinum response during first-line chemotherapy in ovarian cancer?

Tumour Biol. 2014 Jul;35(7):7009-15. doi: 10.1007/s13277-014-1836-x. Epub 2014 Apr 21.

Abstract

Actually, in literature there are not valid tools able to predict the chemotherapy response during first-line ovarian cancer treatment. CA125 and human epididymis protein 4 (HE4) levels of consecutive single-institution patients with epithelial ovarian cancer (EOC) were measured during first-line chemotherapy and until 6 months follow-up. First, patients were divided into two groups according to a temporal criterion: patients treated during 2009 (group A: training group) and patients treated during 2010 (group B: verification group). At sixth months follow-up, patients were sub-classified, within both groups, as platinum resistant or platinum sensitive/intermediate, according to Response Evaluation Criteria in Solid Tumors criteria, and the serum marker courses were further analyzed in each subgroup. Moreover, we performed a logistic regression analysis to choose CA125 and HE4 levels that are best fitted to predict chemoresponse. A total of 76 patients were divided into two groups: group A (n = 42) and group B (n = 34). After 6 months of follow-up, 40 patients were classified as platinum sensitive/intermediate and 36 as platinum resistant. At third chemotherapy cycle, in platinum-resistant patients, HE4 levels were >70 pmol/L in 36 of 36 cases, although in platinum-sensitive/intermediate patients, HE4 levels were >70 pmol/L only in six of 40 cases (sensitivity 100 %, specificity 85 %). Moreover, HE4 reduction of almost 47 % at third chemotherapy cycle reached the sensitivity of 83 % with a specificity of 87 % (positive predictive value = 0.86, negative predictive value = 0.85) in predicting chemoresponse. On the contrary, CA125 values during chemotherapy did not result statistically significant in predicting platinum response. Our findings suggest that HE4 values during first-line chemotherapy could predict chemotherapy response in EOC patients.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Pharmacological / blood*
  • Biomarkers, Tumor / blood
  • CA-125 Antigen / blood
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / pathology
  • Platinum / therapeutic use
  • Prognosis
  • Proteins / genetics
  • Proteins / metabolism*
  • WAP Four-Disulfide Core Domain Protein 2

Substances

  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • CA-125 Antigen
  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human
  • Platinum