ABSTRACT
Effective methods for predicting tumor response to preoperative chemotherapy are required. Aldo-ketoreductase family 1 member B10 (AKR1B10) is predominantly expressed in the gastrointestinal tract and serves an important function in cancer development and progression. The present study investigated whether AKR1B10 expression may predict the therapeutic response of locally advanced gastric cancer. A total of 53 patients with gastric cancer underwent neoadjuvant chemotherapy followed by surgery between January 2006 and December 2015. The protein expression level of AKR1B10 was determined in paraffin-embedded biopsy specimens using immunohistochemistry. Western blotting confirmed that the AKR1B10 protein is primarily localized to the cytoplasm. χ2 and Fisher's exact tests were used to determine the association of AKR1B10 with a number of clinic opathological features. Univariate and multivariate analyses were used to identify the prognostic factors. Survival rates were compared using Kaplan-Meier curves with a log-rank test. The positive rate of AKR1B10 protein expression was 58.5%, whereas 41.5% samples exhibited negative expression. The frequency of AKR1B10-positive gastric cancer samples was increased in patients with lymph node metastasis and decreased in those exhibiting tumor regression. The 5-years overall survival rate for the AKR1B10-positive group was significantly poorer than that for the AKR1B10-negative group. AKR1B10 expression was associated with lymph node metastasis and a poorer prognosis, along with a poor response to neoadjuvant chemotherapy suggesting that AKR1B10 may be a potential predictor for the therapeutic response of locally-advanced gastric cancer.
ABSTRACT
OBJECTIVE: The aim of the study reported here was to identify whether a stem cell biomarker, Lin28, may predict the pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: The study enrolled 47 patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery between July 2004 and March 2012. Cancer tissue was biopsied by gastroscopy and Lin28 expression in the tissue was measured by immunohistochemistry. Statistical analyses were performed to identify the relationship between Lin28 expression and tumor regression grade. RESULTS: Of the 47 cases, pathologic nonresponse was observed in 29 (61.7%) and pathologic response in 18 (38.3%). Receiver-operating characteristic curve analysis showed that the histoscore of Lin28 expression with 0.325 as a cutoff value could differentiate between pathologic response and nonresponse. Multivariable analysis showed that Lin28 expression was an independent predictive factor for pathologic response to neoadjuvant chemotherapy (P = 0.006). CONCLUSION: Lin28 expression was associated with pathologic tumor response in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. This may suggest that Lin28 can serve as a predictive biomarker for neoadjuvant chemotherapy in patients with gastric cancer.
ABSTRACT
BACKGROUND AND OBJECTIVES: To identify clinicopathologic variables that could predict pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: The study enrolled 108 patients who underwent neoadjuvant chemotherapy followed by surgery between July 2004 and December 2010. Tumor responses to neoadjuvant chemotherapy were assessed in terms of tumor regression. Statistical analyses were performed to identify factors associated with pathologic tumor response. RESULTS: Tumor regression was found in 22.2% (24/108) patients, patients with tumor regression observed better overall survival as compared to that of patients without tumor regression. Univariate and multivariate analyses observed that both tumor differentiation and tumor size were independent predictors of tumor regression. CONCLUSIONS: This study suggests that both tumor differentiation and tumor size is the most important clinical predicator of pathologic tumor response, it may be of benefit in the selection of treatment options in locally advanced gastric cancer.
Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/therapy , Neoadjuvant Therapy , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Adenocarcinoma/pathology , Adult , Aged , Female , Gastrectomy , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Prognosis , Sex Distribution , Stomach Neoplasms/pathologyABSTRACT
Previous reports had indicated that there was a possible correlation of dystroglycan (DG) with biological behavior of cancer cells and cancer patients' survival. However, the role of DG expression in gastric cancer was rarely studied. In this study, α-DG and ß-DG expression were determined by immunohistochemistry in specimens of primary cancer, metastatic lymph node, distal metastatic lesion, and their normal counterpart tissues in 20 gastric cancer patients. Correlations between α-DG and ß-DG expression and prognosis were retrospectively analyzed. Our results found that positive expression of α-DG in normal mucosa, paired primary tumor, metastatic lymph node and distal metastatic site was detected in 95%, 70%, 25%, and 5% specimens, individually. Regarding ß-DG,it was 70%, 55%, 10%, and 10%, individually. Patients who had lower α-DG expression in tumors than in normal counterparts showed poor survival (p = 0.002), whereas such a correlation was not found in the case of ß-DG (p = 0.079). Difference of α-DG between primary tumor and its normal counterparts was an independent prognostic factor in gastric cancer with distal metastasis. This study showed DG expression was gradually reduced during tumor progression. Different expression of α-DG, but not ß-DG, between primary tumor and normal specimen, correlated with patient survival, implicating a potential marker for gastric cancer prognosis.
