Nuclear overexpression of DNA damage-inducible transcript 4 (DDIT4) is associated with aggressive tumor behavior in patients with pancreatic tumors.

DNA damage-inducible transcript 4 (DDIT4) is induced in various cellular stress conditions. Several studies showed that the dysregulation of DDIT4 is involved in different malignancies with paradoxical expressions and roles. Therefore, this study investigated the clinical significance, prognostic, and diagnostic value of DDIT4 in different types of pancreatic tumors (PT). The expression of DDIT4 and long non-coding RNA (TPTEP1) in mRNA level was examined in 27 fresh PT samples using Real-time quantitative PCR (RT-qPCR). Moreover, 200 formalin-fixed paraffin-embedded PT tissues, as well as 27 adjacent normal tissues, were collected to evaluate the clinical significance, prognostic, and diagnosis value of DDIT4 expression by immunohistochemistry (IHC) on tissue microarrays (TMA) slides. The results of RT-qPCR showed that the expression of DDIT4 in tumor samples was higher than in normal samples which was associated with high tumor grade (P = 0.015) and lymphovascular invasion (P = 0.048). Similar to this, IHC findings for nucleus, cytoplasm, and membrane localization showed higher expression of DDIT4 protein in PT samples rather than in nearby normal tissues. A statistically significant association was detected between a high level of nuclear expression of DDIT4 protein, and lymphovascular invasion (P = 0.025), as well as advanced TNM stage (P = 0.034) pancreatic ductal adenocarcinoma (PDAC) and in pancreatic neuroendocrine tumor (PNET), respectively. In contrast, a low level of membranous expression of DDIT4 protein showed a significant association with advanced histological grade (P = 0.011), margin involvement (P = 0.007), perineural invasion (P = 0.023), as well as lymphovascular invasion (P = 0.005) in PDAC. No significant association was found between survival outcomes and expression of DDIT4 in both types. It was found that DDIT4 has rational accuracy and high sensitivity as a diagnostic marker. Our results revealed a paradoxical role of DDIT4 expression protein based on the site of nuclear and membranous expression. The findings of this research indicated that there is a correlation between elevated nuclear expression of DDIT4 and the advancement and progression of disease in patients with PT. Conversely, high membranous expression of DDIT4 was associated with less aggressive tumor behavior in patients with PDAC. However, further studies into the prognostic value and biological function of DDIT4 are needed in future studies.

Comparing Efficacy of Preoperative neo-Adjuvant Chemotherapy and Surgery versus Surgery Alone in Patients with Resectable Gastroesophageal Cancer.

BACKGROUND: Recent researches have led to find strategies to prevent relapse and to improve survival for gastric cancer patients, including preoperative neo-adjuvant approaches. However, the efficacy of some neo-adjuvant regimens including 5-fluorouracil, cisplatin, and docetaxel have been less investigated. The present study evaluated the outcome and mid-term survival of patients with gastric cancer who undergoing this regimen. METHODS: In a randomized double-blinded controlled trial performed at the Firoozgar hospital in Tehran in 2011-12, 61 patients were randomly assigned to treatment (32 to neo-adjuvant chemotherapy with docetaxel, cisplatin and 5-fluorouracil (5-FU) before surgery and 27 to surgery alone). The present study tried to assess the efficacy of neoadjuvant chemotherapy regarding improvement of mid-term survival, complications, and R0 resection status. RESULTS: The two groups were matched in terms of gender, mean age, cancer location, and TNM staging. However, R0 resection in the former group was 85.7%; while this indicator in the isolated surgery group was significantly lower (61.5%). Regarding WHO performance, no significant difference was observed across the two groups. Patients in neo-adjuvant chemotherapy group were followed for mean follow-up time 10.32 months and those who categorized in isolated surgery group were followed for mean follow-up time 10.88 months. Mid-term mortality rate in the two groups was 14.3% and 15.4%, respectively (p = 0.866). In this regard, 3-, 6-, and 9-month survival rate in neo-adjuvant chemotherapy group was 96.4%, 89.3%, and 85.7%, respectively. These survival rates in the surgery group were 92.3%, 88.5%, and 84.6%, respectively. Multivariable logistic regression analysis showed that among all study variables, only R0 resection status could predict mid-term mortality. CONCLUSION: Neo-adjuvant chemotherapy and surgery compare to surgery alone more improve R0 resection status, but mid-term survival rate is similar in the two regiments. R0 resection status can effectively predict appropriate mid-term survival in undertreated patients.