Reversal of Chemotherapy Resistance to Cisplatin in NSCLC by miRNA-195-5p via Targeting the FGF2 Gene.

OBJECTIVE: To explore the mechanism of miR-195-5p in the pathogenesis non-small cell lung cancer (NSCLC) and cisplatin resistance. METHODS: The function of miR-195-5p in NSCLC and cisplatin resistance were determined by MTT, scratch assay, transwell assay, and nude mice xenograft experiments. miR-195-5p target gene was identified by dual-luciferase reporter assays and real-time PCR analysis. RESULTS: miR-195-5p content was lower in A549/DDP than that in A549 cells, with reduced chemotherapy sensitivity and increased cell invasion and migration ability. The loss-of-function and gain-of-function assays illustrated that miR-195-5p might have increased the chemosensitivity to cisplatin in the A549/DDP cells and decreased cell migration and invasion. FGF2 is a negatively correlated action target of miR-195-5p. miR-195-5p might affect EMT by inhibiting FGF2. Overexpression of FGF2 resulted in enhanced cisplatin resistance in the cells, while miR-195-5p might have reversed this resistance. CONCLUSION: Overall, miR-195-5p might target FGF2 to reduce cisplatin resistance in A549/DDP cells and enhance chemosensitivity.

Adjuvant radiotherapy for patients with pathologic node-negative esophageal carcinoma: A population based propensity matching analysis.

BACKGROUND: The impact of adjuvant treatment for esophageal carcinoma with tumor-negative lymph nodes after upfront radical esophagectomy is still uncertain. This study investigated the effects of postoperative radiotherapy in pT1-3N0 esophageal carcinoma after radical resection. METHOD: We retrospectively identified pT1-3N0M0 esophageal carcinoma patients between 2000 and 2016 from the Surveillance, Epidemiology, and End Results database. Patients with upfront esophagectomy were categorized as having received surgery alone (SA) and surgical resection followed by adjuvant radiotherapy (SA + RT). Propensity score matching, univariate and multivariate analysis were performed to compare overall survival (OS) and cause-specific survival (CSS). RESULTS: A total of 2862 patients were identified, of whom 274 received SA + RT and 2588 received SA. The median follow-up was 60.4 months (95%CI, 58.7-62.1 months). The five-year OS and CSS were better for SA group compared with SA + RT group (P < 0.001, respectively). Furthermore, after matching, the OS and CSS were still significantly better for SA patients. For T subgroup analysis, postoperative radiotherapy was an independent prognostic factor only for pT1 patients with worse OS, without survival differences for pT2 and pT3 patients. However, after multivariate cox analysis, postoperative radiotherapy can provide significantly better OS for pT3 patients with tumor length ≥5 cm (P = 0.03; 95%CI, 0.29-0.94). CONCLUSIONS: Among pT1-3N0M0 esophageal carcinoma patients, postoperative radiotherapy can provide significantly better OS for pT3 patients with tumor length ≥5 cm. However, there are no survival benefits for pT1-2 patients after SA + RT procedure. This finding may have significant implications on the use of adjuvant radiation in patients with pN0 disease.

Association of Kruppel-like factor 4 expression with the prognosis of esophageal squamous cell carcinoma patients.

OBJECTIVE: To investigate the association of Kruppel-like factor 4 (KLF4) expressions with the prognosis of esophageal squamous cell carcinoma (SCC) patients. METHODS: Ninety-eight cases of esophageal carcinoma patients were enrolled. The expression of KLF4 in the esophageal SCC and normal esophageal mucosa tissues were examined by immunohistochemistry. The correlations between the expression of KLF4 protein and patients' clinical characteristics and prognosis were analyzed. RESULTS: We observed higher expressed KLF4 in normal esophageal mucosa tissues than esophageal SCC tissues, with positive rate of 82.7% (81/98) and 43.8% (43/98) respectively. In patients with lymphatic metastasis, the positive rate of KLF4 was 24.4% (10/41), whereas it was 57.9% (33/57) in patients without lymphatic metastasis, and the difference was significant (x(2) = 10.871, P = 0.001). The positive rates of KLF4 were 62.5% (5/8), 53.1% (26/49) and 29.3% (12/41) in stage I, II and III patients, respectively. There were no correlations between the expression of KLF4 and gender, age, tumor size, location, differentiation grade and infiltration depth. The 5-year survival rates and median survival times were 48.8% and 25.5%, and 55 and 26 months for the patients with KLF4 positive and negative expression, respectively. There were significant differences between the patients with KLF4 positive expression and negative expression in the 5-year survival rates and median survival times (x(2) = 5.747 and 4.493, P = 0.017 and 0.034). CONCLUSION: KLF4 might act as a tumor suppressor in esophageal SCC and the expression status of KLF4 could be considered as a prognosis predictor for esophageal SCC patients.

Extranodal metastasis is a powerful prognostic factor in patients with adenocarcinoma of the esophagogastric junction.

BACKGROUND AND OBJECTIVES: The purpose of this study is to estimate the effect of extranodal metastasis (EM) on recurrence and survival in patients with adenocarcinoma of the esophagogastric junction (AEG) after curative resection. METHODS: Clinical data from 284 node-positive AEG patients who underwent curative resection were reviewed. Univariate and multivariate analyses were conducted to elucidate the effect of EM on recurrence-free survival (RFS) and overall survival (OS). RESULTS: EM was detected in 70 (24.6%) of the 284 cases. It had a significant correlation with tumor size, Lauren type, histopathological grading, depth of tumor invasion, number of metastatic nodes, lymph node ratio, and TNM stage. The 5-year RFS and OS rates were 22.2% and 24.3%, respectively. Patients with EM had a significantly decreased RFS (16 vs. 36 months, P < 0.001) and OS (23 vs. 41 months, P < 0.001) compared with those without EM. Multivariate analyses identified EM as an independent prognostic factor (P = 0.003 and 0.001, respectively). CONCLUSION: The presence of EM increases recurrence probability and reduces OS probability of AEG patients with lymph node metastasis. EM is a powerful prognostic factor reflecting a particularly aggressive biological behavior. Better understanding of EM status can help clinicians with regard to treatment decision and prognosis evaluation.

[Prognostic value of metastatic lymph node ratio in adenocarcinoma of the gastroesophageal junction].

OBJECTIVE: To compare the prognostic value of AJCC/UICC pN stage with metastatic lymph node ratio (MLR) and the prognostic difference between the tumor-node-metastasis (TNM) stage and tumor-ratio-metastasis (TRM) stage in patients with adenocarcinoma of the gastroesophageal junction. METHODS: Clinical data of 414 patients with adenocarcinoma of the gastroesophageal junction undergoing curative resection at the Tianjin Medical University Cancer Institute and Hospital from January 2000 to June 2007 were retrospectively reviewed. Spearman correlation analysis was performed to examine the correlations between pN, MLR and retrieved nodes. Univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis were performed to analyze the effects of pN, MLR, TNM and TRM stage on the prognosis of these patients. The area under the ROC curve (AUC) was plotted to compare the value of these stages and to predict the 5-year survival rate. RESULTS: The median number of retrieved nodes was 17 (4-71) per patient, and the median number of positive nodes was 4 (0-67) per patient. The number of metastatic lymph node was positively correlated with that of retrieved nodes (P<0.01), but MLR was not correlated with the number of retrieved nodes (P>0.05). Univariate and multivariate survival analysis showed that either pN or MLR could be used as an independent risk factor for survival (P<0.01) and the hazard ratio of MLR stage was larger than that of pN stage (1.573 vs 1.382). While pN and MLR were entered into the Cox hazard ratio model as covariates at the same time, MLR remained as the independent prognostic factor (P<0.01), but pN lost significance (P>0.05). The AUC of MLR and pN staging was 0.726 and 0.714, and of TRM and TNM staging was 0.747 and 0.736, respectively, however the differences were not statistically significant (all P>0.05). CONCLUSIONS: MLR is an independent prognostic factor for patients with adenocarcinoma of the gastroesophageal junction. The value of MLR and TRM staging systems may be superior to pN and TNM staging systems in evaluating the prognosis of these patients.

[Analysis of the clinicopathologic characters and prognostic impact of extranodal metastasis in gastric cardia patients].

OBJECTIVE: To investigate the correlation between extranodal metastasis (EM) and clinicopathologic features as well as the effect of EM on the prognosis in gastric cardia patients. METHODS: Retrospective analysis was performed for the 323 cases with histologically proven adenocarcinoma of gastric cardia who underwent curative resection from January 2000 to January 2007. There were 272 male patients and 51 female patients with their median age of 63 (22 to 85) years. The relationship between clinicopathological features and extranodal metastasis was studied. The effects of the EM on the recurrence and survival of these patients were also analyzed. RESULTS: EM positive was detected in 67 (20.7%) of the 323 patients. The incidence of EM was correlated with tumor Lauren typing, differentiation degree, invasive depth and lymph node metastasis (χ(2) = 4.647-27.216, P < 0.05). The 5-year survival rate and media survival time between patients with EM and those without EM were 12.3%, 34.1% and 20, 39 months, there was a statistically significantly difference (χ(2) = 23.936, P = 0.000) in 5-year survival rate. Multivariate analysis identified that invasive depth, lymph node metustasis and EM as an independent prognostic factor of all the patients. To the last follow up, the cumulative probability of recurrence of EM-positive patients was significant higher than EM-negative patients (59.7% vs. 35.9%; χ(2) = 12.409, P = 0.000). To study furthermore, stratified analysis showed that, in the node-positive patients, the cumulative recurrence rate of EM-positive patients was higher than EM-negative patients (60.9% vs. 40.0%; χ(2) = 8.410, P = 0.004) and the 5-year survival rate of EM-positive patients was less than the EM-negative patients (12.9% vs. 30.1%; χ(2) = 12.939, P = 0.000), the differences were statistically significant. CONCLUSIONS: EM positive is determined to be an independent prognosis factor of gastric cardia after curative resection. EM-positive patients have a high risk for recurrence and a short time to live.

[Risk factors of early recurrence and prognosis for patients with adenocarcinoma of gastroesophageal junction after curative resection].

OBJECTIVE: To investigate the risk factors for early recurrence of gastroesophageal junction adenocarcinoma (Siewert type II/III) after curative resection and the prognosis of these patients. METHODS: Retrospective analysis was performed for the 170 patients with recurrent AEG after curative resection in our hospital.Univariate and multivariate analysis were applied to investigate risk factors for early recurrence ( < 24 month), the prognosis of these patients were also analyzed. RESULTS: The rate of early recurrence of AEG after curative resection was 75.3%. Univariate analysis showed that tumor Borrmann type, invasive depth, lymph node metastasis, metastasis lymph node ratio (LNR) and TNM stage were significant factors associated with early recurrence after curative resection (P < 0.05). Multivariate analysis identified that only LNR and tumor invasive depth were independent risk factors for early recurrence (P < 0.05). The median disease free survival time (9, 20 months, P < 0.01), 5-year survival rate (2.4%, 12.6%, P < 0.01) and the median survival time after recurrence(5, 8 months, P = 0.004) between patients with high-LNR group and low-LNR group were significantly difference. CONCLUSIONS: LNR and tumor invasive depth were determined to be independent risk factors associate with early recurrence after curative resection for AEG. The patients with high-LNR have a poorer survival compared with those with low-LNR; For the patients with serosa invaded and high LNR should be closely followed up to detect recurrence and take effective treatment timely to improve patients outcomes.