Objective  To investigate the expression and clinicopathological significance of lactate dehydrogenase A (LDHA) in different grades of gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

  Methods  Totally, 112 patients with GEP-NETs, who underwent endoscopic and surgical resection from January 2013 to December 2018, were recruited at the Affiliated Hospital of Qingdao University. The patients were designated as grade 1 (G1, n=43), grade 2 (G2, n=17), grade 3 (G3, n=52) according to Ki-67 index and mitotic rate. LDHA expression in the different grades of GEP-NET tissue was determined by immunohistochemistry. The correlation between LDHA expression in GEP-NET tissue and clinicopathological characteristics, in addition to survival time, was analyzed. The data were also analyzed for correlations between LDHA expression and both serum LDH and classic neuroendocrine markers. All analyses were performed using the Chi-squared test and Kaplan-Meier survival curves. The log-rank test was used for comparison of survival between groups.

  Results  LDHA expression levels in GEP-NET tissues were different for the three grades (P < 0.001), and there was a positive correlation between grade and expression level. The positive expression rate of G1 was 48.8%, that of G2 was 70.6%, and of G3 was 86.5%. Clinicopathological analysis showed that LDHA expression in GEP-NETs was correlated with gender, tumor size, TNM staging, infiltration depth, and lymph node metastasis (all P < 0.05). Kaplan-Meier survival curves and the log-rank test showed that the survival rate in patients with high LDHA expression was significantly lower than that in the low- expression group (P=0.005).

  Conclusions  LDHA expression level is different in GEP-NET patients with different grades, and increased expression level indicates poor patient prognosis.