Identification of Sensitivity Predictors of Neoadjuvant Chemotherapy for the Treatment of Adenocarcinoma of Gastroesophageal Junction

Abstract

The identification of reliable predictors of chemotherapy sensitivity and early screening of adenocarcinoma of gastroesophageal junction (AGEJ) patients who are resistant to chemotherapy has become an important area of clinical and translational research. We aimed to investigate the predictive value of seven cancer-associated cellular proteins for neoadjuvant chemotherapy in AGEJ patients. Clinical data of 93 patients who received neoadjuvant chemotherapy for locally advanced AGEJ between June 2010 and December 2014 were reviewed. All patients were administered the combination regimen of S-1 and oxaliplatin (SOX). Expression of P-glycoprotein (P-gp), glutathione S-transferase-π (GST-π), topoisomerase II (topo II), multidrug resistance gene-associated protein (MRP), lung resistance-related protein (LRP), Ki-67, and p53 was determined by immunohistochemistry (IHC) in AGEJ tissues before neoadjuvant chemotherapy. Chemotherapeutic efficacy was evaluated according to RECIST 1.0 standards and histopathological results, and the relationship between the expression of the cellular proteins and chemotherapy efficacy was analyzed. The SOX regimen was associated with an overall response rate of 46.2%. The frequency of expression of the seven cancer-associated factors in the AGEJ tissues was as follows: P-gp, 64.5%; GST-π, 39.8%; topo II, 72.0%; MRP, 33.3%; LRP, 68.8%; Ki-67, 62.4%; and p53, 40.9%. Expression of Ki-67 (p = 0.003) and p53 (p = 0.009) was significantly correlated with chemotherapy sensitivity. Elevated Ki-67 expression and decreased p53 expression predict for SOX insensitivity in AGEJ, and the cellular expression of these respective proteins may provide a useful reference for designing individualized chemotherapy regimens for AGEJ patients in the future.

Impact of Tumor Localization and Molecular Subtypes on the Prognostic and Predictive Significance of p53 Expression in Gastric Cancer

“…In our analysis of the biopsy cohort before CTx treatment, we did not find an association with response to therapy in terms of tumor regression or with respect to the survival of the patients. This is in line with a report analyzing only a small number of pretherapeutic tumor biopsies [24], whereas other studies reported that mutated or aberrant expression of p53 indicated chemoresistance [25][26][27]. These inconsistent results may be due to various reasons related to the complexity and functional diversity of p53 and p53 mutations, as well as to differences in the applied chemotherapeutic regimens and in patient characteristics, while methodical aspects of p53 determination most likely play a role.…”

Ki-67 labeling index as a prognostic marker in advanced stomach cancer

“…Similarly, in the cases of breast cancer, a high Ki-67 LI value is associated with higher response rate to chemotherapy, as seen in the neoadjuvant treatment arm [1819]. Moreover, Li et al [20] recently reported that gastroesophageal cancer showed good response to chemotherapy in cases with elevated Ki-67 expression.…”

Prognostic Value of Combination of Pretreatment Red Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio in Patients with Gastric Cancer

“…Nevertheless, there are still some patients with the same TNM stage and different prognosis [ 10 ]. Although a few of molecular markers are identified to stratify survival in different cohorts of GC patients [ 11 – 14 ], simple, inexpensive, and valid signatures to generate prognostic model are still unavailable at clinical settings.…”