Possible Predictive Markers of Response to Therapy in Esophageal Squamous Cell Cancer

Pathol Oncol Res. 2019 Jan;25(1):279-288. doi: 10.1007/s12253-017-0342-z. Epub 2017 Nov 4.

Abstract

The aim of the present study was to investigate the relationship between the intensity of biomarker expression and the response to radiochemotherapy in patients with advanced esophageal squamous cell cancer (ESCC). Ninety-two patients with locally advanced ESCC were examined retrospectively. Pre-treatment tumor samples were stained for proteins SOUL, Hsp 16.2, Growth Hormone-Releasing Hormone Receptor (GHRH-R) and p-Akt using immunhistochemistry methods. Kaplan-Meier curves were used to show the relationship between intensity of expression of biomarkers and clinical parameters and 3-year OS. A significant correlation was found between high intensity staining for Hsp 16.2, p-Akt and SOUL and poor response to NRCT. Application of a higher dose of radiation and higher dose of cisplatin resulted in better clinical and histopathological responses, respectively. Among the clinical parameters, the localization of the tumor in the upper-third of the esophagus and less than 10% weight loss were independent prognostic factors for increased 3-year OS. Hsp16.2, p-Akt and SOUL are predictors of negative response to NRCT, therefore these biomarkers may become promising targets for therapy. Furthermore, level of expression of p-Akt, weight loss and the localization of the tumor are significant factors in the prediction of OS in ESCC.

Keywords: AKT; Esopageal cancer; Predictiv factors; Radiochemotherapy; Small heat shock protein.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy / mortality*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / therapy
  • Female
  • Follow-Up Studies
  • Heme-Binding Proteins
  • Hemeproteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Middle Aged
  • Pregnancy Proteins / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • HEBP2 protein, human
  • HSPB11 protein, human
  • Heme-Binding Proteins
  • Hemeproteins
  • Intracellular Signaling Peptides and Proteins
  • Pregnancy Proteins
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt