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Esophageal cancer is a high occult malignant tumor. Even with good diagnosis and treatment, the 5-year survival rate of esophageal cancer patients is still less than 30%. Considering the influence of clinical characteristics on postoperative esophageal cancer patients, the construction of a neural network model will help improve the poor prognosis of patients in the five years. In this study, genetic algorithm optimized deep neural network is exploited to the clinical dataset of esophageal cancer. The independent prognostic factors are screened by Relief algorithm and Cox proportional risk regression. FTD prognostic staging system is established to assess the risk level of esophageal cancer patients. FTD staging system and independent prognostic factors are integrated into the genetic algorithm optimized deep neural network. The Area Under Curve (AUC) of FTD staging system is 0.802. FTD staging system is verified by the Kaplan-Meier survival curve, and the median survival time is divided for different risk grades. The FTD staging system is superior to the TNM stages in the prognosis effect. The AUC of deep neural network optimized by genetic algorithm is 0.91. The deep neural network optimized by genetic algorithm has good performance in predicting the 5-year survival status of esophageal cancer patients. The FTD staging system has a significant prognostic effect. The FTD staging system and genetic algorithm optimized deep neural network can be successfully availed in clinical diagnosis and treatment. • Find the most suitable prediction model method: feature selection-deep learning. • Select the strong survival correlation feature set from Clinical dataset. • FTD system predicts the median survival time of patients at different stages. • GA optimized DNN to improve the model accuracy of esophageal cancer. • GA-DNN is successfully applied to a non-image continuous dataset. [ABSTRACT FROM AUTHOR]

The correlations of murine double minute 2 ( MDM2) T309 G and esophageal cancer were elucidated because the association between MDM2 expression states and clinicopathological parameters of esophageal squamous cell carcinoma ( ESCC) is controversial. We conducted a meta-analysis on studies screened from Pub Med, Web of Science, Embase, the Cochrane Library, and the Chinese Biomedical Literature Databases that were published before October 2014. All studies describing the association between MDM2 and ESCC were traced. Meta-analysis was performed using the STATA software ( Stata Corp., College Station, TX, USA). A total of 9 studies with 707 cases and 324 controls were included. MDM2 expression was higher in ESCC than in normal esophageal epithelium (odds ratio [ OR] 10.38, 95% confidence interval [ CI] 6.42-16.78, P < 0.001). High MDM2 expression was associated with early primary tumor stage ( T1/ T2 vs. T3/ T4, OR 0.59, 95% CI 0.38-0.92, P = 0.018) and increased risk of regional lymph node metastasis ( N0 vs. N1, OR 1.66, 95% CI 1.03-2.67, P = 0.039). However, no relationship was observed between MDM2 expression and the risk of distant metastasis ( OR = 2.09, 95% CI 1.00-4.36, P = 0.050), and MDM2 was not significantly correlated with TP53 expression ( OR 1.22, 95% CI 0.53-2.77, P = 0.643). Our analysis suggests that MDM2 acts as a potent marker of early primary tumor stage but higher risk of regional lymph node metastasis in ESCC. However, because of the limited number of studies included, the result should be further clarified by well-designed prospective studies. [ABSTRACT FROM AUTHOR]

Preoperative elevations in the levels of serum amyloid A ( SAA) or C-reactive protein ( CRP) have been reported to be prognostic indicators in several malignancies. The aim of this study is to evaluate the serum levels of SAA and CRP in the prognosis of esophageal squamous cell carcinoma ( ESCC). In total, 252 patients with ESCC who had undergone surgery with curative-intent were retrospectively recruited. The specificity, sensitivity, and prognostic value of SAA or CRP levels were measured as the area under the receiver operating characteristic ( ROC) curve ( AUC). The clinical value of SAA and CRP levels as prognostic indicators was evaluated using Cox's proportional hazards model. The 1-, 3-, and 5-year overall survival ( OS) rates for the entire cohort of patients with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the levels of SAA and CRP was significant ( r2 = 0. 685, P < 0.001). The ROC analysis showed that the levels of CRP were associated with a significantly lower overall accuracy than were the SAA levels ( AUC, 0.615 vs. 0.880; P < 0.001). For the complete cohort, the median OS was 52.0 months longer in patients with low preoperative serum levels of SAA (72.0 months) compared with patients who had high SAA levels (20.0 months, P < 0.001). The median OS among patients with low CRP levels was also longer compared with the patients who had high CRP levels (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that the preoperative elevated levels of SAA could find significant differences in OS for stage I, stage II, and stage III ( P < 0.001, P = 0.001, and P < 0.001, respectively), whereas the increased levels of CRP could only find a difference in OS for stage II cancers. After a multivariate analysis, preoperative elevated level of SAA was found to be an independently and significant prognostic factor ( P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can act as prognostic factors, and that elevated levels of these proteins are associated with negative effects on the survival of patients with ESCC. SAA showed a higher prognostic value than CRP in both cohort and subgroup analysis. [ABSTRACT FROM AUTHOR]

Background:Body mass index (BMI) has been associated with the risk of oesophageal cancer. But the influence of BMI on postoperative complication and prognosis has always been controversial.Methods:In total, 2031 consecutive patients who underwent oesophagectomy between 1998 and 2008 were classified according to Asian-specific BMI (kg m−2) cutoff values. The impact of BMI on overall survival (OS) was estimated using the Kaplan-Meier method and Cox proportional hazard models. We performed a meta-analysis to examine the association of BMI with OS and postoperative complication.Results:Patients with higher BMI had more postoperative complication (P=0.002), such as anastomotic leakage (P=0.016) and cardiovascular diseases (P<0.001), but less incidence of chylous leakage (P=0.010). Logistic regression analysis showed that BMI (P=0.005) was a confounding factor associated with postoperative complication. Multivariate analysis showed that overweight and obese patients had a more favourable survival than normal weight patients (HR (hazard ratio) = 0.80, 95% CI (confidence interval): 0.70-0.92, P=0.001). Subgroup analysis showed that the association with higher BMI and increased OS was observed in patients with oesophageal squamous cell carcinoma (ESCC) (P<0.001), oesophageal adenocarcinoma (EA) (P=0.034), never-smoking (P=0.035), ever-smoking (P=0.035), never alcohol consumption (P=0.005), weight loss (P=0.003) and advanced pathological stage (P<0.001). The meta-analysis further corroborated that higher BMI was associated with increased complication of anastomotic leakage (RR (risk ratio)=1.04, 95% CI: 1.02-1.06, P=0.001), wound infection (RR=1.03, 95% CI: 1.00-1.05, P=0.031) and cardiovascular diseases (RR=1.02, 95% CI: 1.00-1.05, P=0.039), but decreased incidence of chylous leakage (RR=0.98, 95% CI: 0.96-0.99, P<0.001). In addition, high BMI could significantly improved OS (HR=0.78, 95% CI: 0.71-0.85, P<0.001).Conclusion:Preoperative BMI was an independent prognostic factor for survival, and strongly associated with postoperative complications in oesophageal cancer. [ABSTRACT FROM AUTHOR]

SUMMARY The goal of this study was to explore the molecular mechanism of hypoxia inducible factor-1 alpha (HIF-1 alpha) action on migration and invasion of esophageal carcinoma cells. We used cobalt chloride (CoCl2) to mimic tumor hypoxic microenvironment and analyzed the expressions of E-cadherin, matrix metalloproteinase-2 (MMP-2), and HIF-1 alpha in esophageal carcinoma cells under hypoxia by reverse transcription polymerase chain reaction and Western blotting. To analyze the function of HIF-1 alpha in Eca109 and TE1 cells, we established stable HIF-1 alpha knockdown cells using small interfering RNA. Blocking effect was detected by Western blotting. The concentrations of MMP-2 protein in the conditioned medium were also determined by enzyme-linked immunosorbent assay. Wound-healing and cell invasion assay were used to evaluate the migration and invasion of esophageal carcinoma cells. After exposure to hypoxia, expressions of HIF-1 alpha protein in Eca109 and TE1 cells were upregulated, both mRNA and protein levels of E-cadherin were downregulated, and MMP-2 were upregulated ( P < 0.05), whereas HIF-1 alpha mRNA had no significant change ( P > 0.05). Small interfering RNA could block HIF-1 alpha effectively under hypoxia, then enhanced E-cadherin expression and inhibited MMP-2 expression, respectively. Furthermore, expression of HIF-1 alpha protein was stable even though MMP-2 repressed by BB2516. Compared with that in normoxia, Snail expression was enhanced when Eca109 or TE1 cells exposed to hypoxia. Once HIF-1 alpha blocked, Snail expressions were inhibited accordingly. Wound recovery and the number of invading cells decreased ( P < 0.05) after HIF-1 alpha blocked. The hypoxia suppresses E-cadherin expression and enhances MMP-2 expression favoring esophageal carcinoma migration and invasion via HIF-1 alpha activation. Our observations suggest that HIF-1 alpha inhibition might be an effective strategy to weaken the migration and invasion of esophageal carcinoma cells. [ABSTRACT FROM AUTHOR]

SUMMARY The prognosis of esophageal squamous cell carcinoma (ESCC) is poor. It is urgent to improve this situation. Epidermal growth factor receptor (EGFR)-targeted therapy possesses a promising clinical efficacy. Mutations of EGFR and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) have been identified in esophageal carcinoma, but corresponding Chinese data are limited. So we investigated the mutation status of EGFR and KRAS in Chinese patients with ESCC, and explored their correlations with clinicopathological features. Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 50 randomly selected Chinese patients with ESCC. EGFR mutations in exons 18-21 were detected by Scorpions amplification refractory mutation system technology. KRAS mutations in codons 12, 13 were detected by direct sequencing of polymerase chain reaction products. The correlations between clinicopathological features and the mutation status of EGFR and KRAS were analyzed using the Statistical Package for the Social Sciences. In the present study, EGFR mutations were found in 7 (14%) out of 50 patients, including G719X missense mutation ( n= 1), in-frame deletion ( n= 2), and L858R missense mutation ( n= 5). Six (12%) out of 50 patients had KRAS mutations in codon 12. Concurrent EGFR and KRAS mutations were detected in one sample. The presences of EGFR and KRAS mutations were not associated with gender, age, smoking history, cell differentiation, or cancer stage. In conclusion, the incidence of EGFR mutations in Chinese patients with ESCC was higher than that of previous reports, and the incidence of KRAS mutations was not low. EGFR and KRAS mutations were mainly located in exons 19 and 21 and codon 12, respectively. Unlike in NSCLC, concurrent EGFR and KRAS mutations existed. [ABSTRACT FROM AUTHOR]

Objectives: To explore the expression of manganese superoxide dismutase (MnSOD) in esophageal squamous cell carcinoma (ESCC) and its relationship with clinicopathological characteristics and biological behavior. Methods: On 45 patients with ESCC, immunohistochemistry (SP method), reverse transcription-polymerase chain reaction (RT-PCR), and Western blot were used to detect MnSOD protein and mRNA expression in ESCC and in its adjacent normal tissue 5 cm apart from the edge of cancer lesion and without documented microscopic invasive cancer. Meanwhile, the relationship between the pathological features of esophageal cancer and its biological behavior was analyzed. Results: In ESCC and normal esophageal tissue, MnSOD protein expression was identified 31.1% (14/45) and 86.7% (31/45) ( P= 0.000), respectively, with the relative expression levels of MnSOD mRNA 0.310 ± 0.036 and 0.482 ± 0.053 ( P= 0.000), relatively. Western blot study showed that the relative expressions of MnSOD protein in cancer lesion and in adjacent normal tissue were 0.384 ± 0.038 and 0.766 ± 0.041, respectively ( P= 0.000). With longer lesion, deeper invasion, and poorer differentiation, the expression of MnSOD would get lower, indicating that the levels of MnSOD protein and mRNA expression were closely related to the length of lesion, depth of invasion, and degree of differentiation in ESCC ( P < 0.05). Nevertheless, the result showed no association with the presence of lymph node metastasis, cancer location, and macroscopic classification ( P > 0.05). Conclusions: MnSOD protein and mRNA expression both decreased in ESCC, which may be related to carcinogenesis and the development of esophageal cancer. Therefore, detecting the expression of MnSOD in esophageal carcinoma would be of clinical significance in understanding its biological behavior and in guiding therapeutic strategy of esophageal cancer. [ABSTRACT FROM AUTHOR]

Treatment-related pneumonitis (TRP) and radiation recall pneumonitis (RRP) has recently been identified as a toxicity triggered by thoracic irradiation combined with anti-PD-1 mAb in esophageal squamous cell carcinoma (ESCC). However, the incidence, risk factors and dose-volume parameters remain unknown. We analyzed 97 patients with ESCC who received thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 mAb. There were 74 patients of newly diagnosed/locally advanced unresectable esophageal cancer, 22 patients of recurrent after radical resection /metastatic esophagus cancer, and 1 patient of resectable esophageal cancer with neoadjuvant therapy. 41 patients received concurrent thoracic radiotherapy and anti-PD-1 mAb, 56 patients received sequential thoracic radiotherapy and anti-PD-1 mAb. The median radiation dose of PTV was 59.4Gy (range from 45Gy to 66Gy, 1.8Gy-2.2Gy per fraction). TRP and RRP were classified according to the CTCAE version 5.0 and the effect of dose-volume parameters of lung on TRP and RRP was analyzed. The average value of V 5, V 10, V 20, V 30 and MLD of lung was 49.2% (27.9%-73.6%), 35.9% (21.7%-48.6%), 21.3% (12.7%-29.9%), (1.5% -17.5%) and 1092.5cGy (666.9cGy-1569.6cGy), respectively. The incidence of TRP was 46.4% (45/97). 41.2% of patients developed grade 1 or 2 pneumonitis and 4.1% of patients was grade 3 pneumonitis. Of note, there was 1 death probably related with TRP. The incidence of RRP was 14.4% (14/97). 14.4% of patients developed grade 1 or 2 pneumonitis and there was no grade ≥3 RRP. The median onset time of TRP and RRP was 16 weeks after receiving anti-PD-1 mAb (2.6 weeks-65.9 weeks) and 48.9 weeks (27 weeks-91.1 weeks) after thoracic radiotherapy, respectively. Result of multivariate analysis showed that V 5 was an independent risk factor of grade ≥2 TRP (P=0.003, OR=1.106). The incidence of grade ≥2 TRP in the V 5 ≥55.7% group was significantly higher than that in the V 5 <55.7% group (56.5% vs 16.2%). There was only a trend towards higher V 5 , V 30 , V 35 , and MLD related to RRP without statistical significance. We demonstrate a high risk of TRP in ESCC patients receiving thoracic radiotherapy/chemoradiotherapy combined with anti-PD-1 mAb and mostly pneumonitis was grade 1 and grade 2. While the occurrence of RRP is relatively less and the severity is mild. TRP (grade≥2) is associated with V 5 ≥55.7%, so clinicians should pay more attention to restriction of V 5 and V 5 <55.7% might be a safer volume. Therapy strategy combined thoracic radiotherapy/chemoradiotherapy with anti-PD-1 mAb might be a safe choice, it is worth a further exploration. [ABSTRACT FROM AUTHOR]