Identification of a prognostic DNA repair gene signature in esophageal cancer.

Background: DNA repair plays a crucial role in the development and progression of different types of cancers. Nevertheless, little is known about the role of DNA repair-related genes (DRRGs) in esophageal cancer (EC). The present study aimed to identify a novel DRRGs prognostic signature in EC. Methods: Gene set enrichment analysis (GSEA) was performed to screen 150 genes related to DNA repair, which is the most important enrichment gene set in EC. Univariate and multivariate Cox regression analyses were used to screen DRRGs closely associated with prognosis. The difference in the expression of hub DRRGs between tumor and normal tissues was analyzed. Combined with clinical indicators (including age, gender, and tumor stage), we evaluated whether the 4-DRRGs signature was an independent prognostic factor. In addition, we evaluated the prediction accuracy using a receiver operating characteristic (ROC) curve and visualized the model's performance via a nomogram. Results: Four-DRRGs (NT5C3A, TAF9, BCAP31, and NUDT21) were selected by Cox regression analysis to establish a prognostic signature to effectively classify patients into high- and low-risk groups. The area under the curve (AUC) of the time-dependent ROC of the prognostic signature for 1- and 3-year was 0.769 and 0.720, respectively. Compared with other clinical characteristics, the risk score showed a robust ability to predict the prognosis in EC, especially in the early stage of EC. Furthermore, we constructed a nomogram to interpret the clinical application of the 4-DRRGs signature. Conclusions: In conclusion, we identified a prognostic signature based on the DRRGs for patients with EC, which can contribute independent value in identifying clinical outcomes that complement the TNM system in EC.

Lymph node metastasis in early invasive lung adenocarcinoma: Prediction model establishment and validation based on genomic profiling and clinicopathologic characteristics.

BACKGROUND: The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next-generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed. METHODS: Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort. RESULTS: Twenty-four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN-positive tumors showed higher mutant allele tumor heterogeneity (p < 0.05), higher tumor mutation burden (p < 0.001), as well as more frequent KEAP1 (p = 0.001), STK11 (p = 0.004), KRAS (p = 0.007), CTNNB1 (p = 0.017), TP53, and ARID2 mutations (both p = 0.02); whereas low frequency of EGFR mutation (p = 0.005). A predictive nomogram involving male sex, solid tumor morphology, higher T stage, EGFR wild-type, and TP53, STK11, CDKN2A, KEAP1, ARID2, KRAS, SDHA, SPEN, CTNNB1, DICER1 mutations showed outstanding efficiency in both the training cohort (AUC = 0.819) and the test cohort (AUC = 0.780). CONCLUSION: This study suggests that the integration of genomic profiling and clinical features identifies early-invasive LUAD patients at higher risk of LN metastasis. Improved identification of LN metastasis is beneficial for the optimization of the patient's therapy decisions.

Development and validation of a prognostic model based on RNA binding proteins in patients with esophageal cancer.

Background: RNA-binding proteins (RBPs) play a crucial role in regulating RNA turnover and are associated with cancer development. However, little is known about the role of RBPs in esophageal cancer (ESCA). The present study focuses on the association between RBP gene expression and survival in ESCA, addressing the clinical relevance of an RBPs-based prediction model for prognosis. Methods: RNA-sequencing data and clinical information of patients with ESCA were obtained from The Cancer Genome Atlas (TCGA) database. We identified differentially expressed genes in ESCA and intersected them with RBP-encoding genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with the identified differentially expressed RBPs. Then, a protein-protein interaction (PPI) network was constructed through the STRING database to determine the hub RBPs. Univariate Cox regression analysis and multivariate Cox regression analysis were applied to construct a novel prognostic model based on RBPs. Based on the R package "Caret", we divided patients into the training set and validation set. The efficacy of the prognostic model was evaluated by the area under the receiver operating characteristic (ROC) curve. A nomogram was developed for the prediction of patient survival outcomes. Results: A total of 158 ESCA patients from the TCGA database were included in our analysis. We screened out five prognostic RBPs (CLK1, CIRBP, MRPL13, TNRC6A, and TYW3) through univariate and multivariate Cox regression analysis. CLK1, CIRBP, TNRC6A and TYW3 were downregulated in tumor samples, while MRPL13 was upregulated. A prognostic model constructed with these five RBPs in the training data set accurately stratified ESCA patients into high- and low-risk groups. When the same prognostic model was applied to the test data set and entire cohort, the 5-RBP signature remained an independent prognostic factor in multivariate analysis. The areas under the time-dependent ROC curve of the prognostic model for predicting one-year survival in the training data set, test data set, and entire cohort were 0.789, 0.753, and 0.764, respectively, confirming that this model is a good prognostic model. The nomogram based on the five RBPs and clinical variables could improve individualized outcome predictions and highlight the importance of RBPs in the outcomes of patients with ESCA. Conclusions: Our study provides a potential prognostic model for predicting the prognosis of ESCA patients. The prognostic nomogram could improve individualized outcome predictions for patients with ESCA, therefore providing novel insights into future diagnosis and treatment.

The prognostic value of an immune-related gene signature and infiltrating tumor immune cells based on bioinformatics analysis in primary esophageal cancer.

Background: Immunotherapy is a promising novel treatment for esophageal cancer (ESCA). However, previous studies provide limited direct information about the prognostic significance of immune-related genes (IRGs) in primary ESCA development. This study explored the prognostic value of IRGs and infiltrating tumor immune cells in primary ESCA. Methods: The ribonucleic acid (RNA)-sequencing data and clinical information of primary ESCA were downloaded from The Cancer Genome Atlas (TCGA) database. Which included the clinical factors and prognosis outcomes of the ESCA patients. The IRGs were downloaded from the ImmPORT database. Results: We established the robust IRG prognostic signature of 4 IRGs (i.e., heat shock protein family A member 6, Oncostatin M, androgen receptor, and nuclear receptor subfamily 2 group F member 2) in primary ESCA, and divided the ESCA patients into high- and low-risk groups based on overall survival (OS). The Kaplan-Meier curves showed the high predictive ability of the prognostic signature in the training, testing, and full data sets (P=2.407e-03, P=1.044e-02, and P=2.535e-04, respectively). Multivariate Cox regression analyses were performed with age, grade, tumor stage, tumor type and the risk score as covariables. The risk score supports the use of a prognostic signature as an independent prognostic factor [training data set: hazard ratio (HR) =1.185, 95% confidence interval (95% CI): 1.013-1.388, P=0.034; testing data set: HR =2.056, 95% CI: 1.015-4.166, P=0.045; full data set: HR =1.197, 95% CI: 1.059-1.354, P=0.004]. The area under the curve (AUC) of the receiver operating characteristic curve validated the high predictive accuracy of the IRG signature in the training, testing, and full data set (AUCs =0.808, 0.657, and 0.751, respectively). The infiltration level of the activated mast cells was significantly higher in the high-risk group than the low-risk group; thus, infiltrating mast cells are associated with worse OS in ESCA patients. Conclusions: Our IRG prognostic signature provides a new direction to predict the survival of primary ESCA patients and has the potential ability to establish, promote, and improve personalized treatment procedures based on each patient's risk.

Single nucleotide polymorphisms in FOXP1 and RORA of the lymphocyte activation-related pathway affect survival of lung cancer patients.

Background: Lymphocyte activation is part of a complex microenvironment that affects the development and progression of solid tumors. The present study analyzed the associations between genetic variants in lymphocyte activation-related genes and survival of patients with non-small cell lung cancer (NSCLC). Methods: Our study evaluated the associations of 14,400 (1,599 genotyped and 12,801 imputed) single-nucleotide polymorphisms (SNPs) in 176 lymphocyte activation pathway-related genes with survival of 1,185 NSCLC patients in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and validated the results in another independent dataset of 984 NSCLC patients from the Harvard Lung Cancer Susceptibility (HLCS) trial. Results: Multivariable Cox proportional hazards regression analyses identified two distinct and possibly functional variants in forkhead box P1 (FOXP1; rs2568847 G>C) and RAR-related orphan receptor A (RORA; rs922782 T>G) that were significantly and independently associated with overall survival (OS) [adjusted hazards ratios (HRs) of 1.21 and 0.82, respectively; 95% confidence intervals (CI), 1.11 to 1.32 and 0.76 to 0.88, respectively; P=5.38×10-6 and 2.68×10-2, respectively]. Combined analysis of the unfavorable genotypes showed a significant correlation with both OS and disease-specific survival (DSS) in patients with NSCLC patients from PLCO trial (both Ptrend<0.0001). Further expression quantitative trait loci (eQTL) analysis using RORA mRNA expression and genotype data in the 1000 Genomes Project demonstrated that the RORA rs922782 G allele predicted mRNA expression levels. Conclusions: Genetic variants in FOXP1 and RORA of the lymphocyte activation pathway may be promising predictors of NSCLC survival. The RORA rs922782 G allele may predict NSCLC survival, possibly by controlling RORA mRNA expression.

Beclin-1 is a Promising Prognostic Biomarker in a Specific Esophageal Squamous Cell Carcinoma Population.

The effects of autophagy and apoptosis in the prognostic assessment and treatment of Esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Here, we conducted a retrospective study on the histopathology of ESCC, investigated the expression of Beclin-1 and Bcl-2 proteins (both autophagy- and apoptosis-related) in esophageal cancer tissue, and analyzed the significance of these proteins for the prognosis of ESCC. In the present study, the expression level of Beclin-1 in ESCC was significantly lower than that in adjacent tissues (p < 0.01), whereas the expression level of Bcl-2 showed the opposite pattern (p < 0.01). Furthermore, low expression of Beclin-1 was associated with more advanced ESCC stages and lymph node metastasis. However, high expression of Bcl-2 was associated with more advanced ESCC stages, deeper tumor invasion, and lymph node metastasis. Moreover, the relationship between Bcl-2 expression and OS was not significant (p > 0.05), whereas Beclin-1 expression was significantly associated with OS (p < 0.05). Subgroup analysis showed that Beclin-1 expression was significantly associated with OS in the high-Bcl-2-expression group but not in the low-Bcl-2-expression group. Importantly, Beclin-1 upregulation or downregulation significantly upregulated or downregulated invasion, respectively, in EC9706 cells in combination with high expression but not low expression of Bcl-2. These findings reveal that differences in autophagy and apoptotic states and their activities may promote malignant tumor differentiation, which could lead to a more aggressive esophageal squamous cell phenotype and a worse survival prognosis. Here, Beclin-1 was shown to be a promising prognostic biomarker and therapeutic target for patients with ESCC in the high-Bcl-2-expression population.

Genetic variants of DOCK2, EPHB1 and VAV2 in the natural killer cell-related pathway are associated with non-small cell lung cancer survival.

Although natural killer (NK) cells are a known major player in anti-tumor immunity, the effect of genetic variation in NK-associated genes on survival in patients with non-small cell lung cancer (NSCLC) remains unknown. Here, in 1,185 with NSCLC cases of a discovery dataset, we evaluated associations of 28,219 single nucleotide polymorphisms (SNPs) in 276 NK-associated genes with their survival. These patients were from the reported genome-wide association study (GWAS) from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. We further validated the findings in an additional 984 cases from the Harvard Lung Cancer Susceptibility (HLCS) Study. We identified three SNPs (i.e., DOCK2 rs261083 G>C, VAV2 rs2519996 C>T and EPHB1 rs36215 A>G) to be independently associated with overall survival (OS) in NSCLC cases with adjusted hazards ratios (HRs) of 1.16 (95% confidence interval [CI] = 1.07-1.26, P = 3.34×10-4), 1.28 (1.12-1.47, P = 4.57×10-4) and 0.75 (0.67-0.83, P = 1.50×10-7), respectively. Additional joint assessment of the unfavorable genotypes of the three SNPs showed significant associations with OS and disease-specific survival of NSCLC cases in the PLCO dataset (P trend<0.0001 and <0.0001, respectively). Moreover, the survival-associated DOCK2 rs261083 C allele had a significant correlation with reduced DOCK2 transcript levels in lung adenocarcinoma (LUAD), while the rs36215 G allele was significantly correlated with reduced EPHB1 transcript levels in lymphoblastoid cell lines in the 1000 Genomes Project. These results revealed that DOCK2 and EPHB1 genetic variants may be prognostic biomarkers of NSCLC survival, likely via transcription regulation of respective genes.

The Prognostic Value of Tumor Mutation Burden and Immune Cell Infiltration in Thymic Epithelial Tumors.

OBJECTIVE: The question of whether the tumor mutation burden (TMB) is associated with either improved survival outcomes or improvement of immunotherapies remains controversial in various malignancies. The aim of this study is to investigate the genomic landscape of the relationship between TMB and immune cell infiltration in thymic epithelial tumors (TETs). METHODS: We downloaded somatic mutation data, transcriptome sequencing data, and clinical information of TETs from the Cancer Genome Atlas (TCGA) database. We assessed the abundance of 22 immune fractions between low-TMB (TMB-L) and high-TMB (TMB-H) groups using the "CIBERSORT" package. RESULTS: Missense mutation had the highest frequency of mutation among the nine variant classifications in TETs. Higher TMB levels were associated with poor survival outcomes (P<0.05), and higher Masaoka stages (P<0.05). More importantly, TMB levels were much higher in the thymic cancer than in thymoma (P<0.01). The infiltration levers of naive CD4(+) T cells and regulatory T cells were significantly higher in the TMB-L group than in the TMB-H group, and this was further associated with better overall survival (OS) in patients with TETs. CONCLUSION: The present study indicates that the prognosis of TMB-H patients with TETs is significantly poorer than is that of TMB-L patients, which might result from the different levels of infiltration of naive CD4(+) T cells and regulatory T cells.

Development and validation of an autophagy-related prognostic signature in esophageal cancer.

BACKGROUND: Autophagy has a dual function in cancer, and its role in carcinogenesis of the esophagus remains poorly understood. In the present study, we explored the prognostic value of autophagy in esophageal cancer (ESCA), one of the leading causes of cancer-related deaths worldwide. METHODS: Using ESCA RNA-sequencing (RNA-Seq) data from 158 primary patients with ESCA, including esophageal adenocarcinoma and esophageal squamous cell carcinoma, were downloaded from The Cancer Genome Atlas (TCGA) for this study. We obtained differentially expressed autophagy-related genes (ARGs) by the "limma" package of R. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses unveiled several fundamental signaling pathways associated with the differentially expressed ARGs in ESCA. Univariate Cox regression analyses were used to estimate associations between ARGs and overall survival (OS) in the TCGA ESCA cohort. A Cox proportional hazards model (iteration =1,000) with a lasso penalty was used to create the optimal multiple-gene prognostic signature utilizing an R package called "glmnet". RESULTS: A prognostic signature was constructed with four ARGs (DNAJB1, BNIP1, VAMP7 and TBK1) in the training set, which significantly divided ESCA patients into high- and low-risk groups in terms of OS [hazard ratio (HR) =1.508, 95% confidence interval (CI): 1.201-1.894, P<0.001]. In the testing set, the risk score remained an independent prognostic factor in the multivariate analyses (HR =1.572, 95% CI: 1.096-2.257, P=0.014). The area under the curve (AUC) of the receiver operating characteristic (ROC) predicting 1-year survival showed a better predictive power for the prediction model. The AUC in training and testing cohorts were 0.746 and 0.691, respectively. Therefore, the prognostic signature of the four ARGs was successfully validated in the independent cohort. CONCLUSIONS: The prognostic signature may be an independent predictor of survival for ESCA patients. The prognostic nomogram may improve the prediction of individualized outcome. This study also highlights the importance of autophagy in the outcomes of patients with ESCA.

Double lung transplantation for Sjögren's syndrome-related interstitial lung disease: a case report and review of literature.

In this study, we present a case of 65-year-old male patient with suspected Sjögren's syndrome-related interstitial lung disease (SS-ILD) with initial symptoms of limb edema and acute respiratory failure. He was treated with immunosuppressor, respiratory support, dialysis, immunomodulatory, and anti-inflammatory medications. However, no significant response was shown to anti-fibrotic treatments and his respiratory function deteriorated. Double lung transplantation was thus indicated considering the irreversible interstitial changes in both lungs. The surgical procedure was complicated, and the role of enhanced recovery after surgery (ERAS) for this critical patient was discussed. The patient experienced hemorrhage, pulmonary infection, and peripheral neuropathy after surgery, but he was cured by the multidisciplinary team. He had a satisfactory quality of life at 1-year follow-up. This case report describes the details of double lung transplantation in a patient with advanced SS-ILD. Important considerations include the indications for and timing of transplantation, the effects of long-term immunosuppression on wound healing, and extrapulmonary organ dysfunction. Based on a review of the published literature and a consideration of the short-term outcomes, lung transplantation for this individual with an autoimmune disease appears to be safe and feasible. SS-ILD should not be a contraindication to transplantation; however, patients with advanced pulmonary involvement should be carefully selected after a multidisciplinary evaluation. More long-term follow-up and further comparative studies are needed in the future.

Beclin-1 expression is associated with prognosis in a Bcl-2-dependent manner in non-small cell lung cancer.

Beclin-1 and Bcl-2 expression abnormalities have been confirmed in different types of cancer. As important regulators of autophagy and apoptosis, respectively, these molecules serve a complex role in tumorigenesis. However, limited information is currently available regarding the association between Beclin-1 and Bcl-2 in (NSCLC). In the present study, the expression levels of Beclin-1 and Bcl-2 were detected in lung cancer tissues, and their prognostic significance was analyzed for NSCLC. A total of 120 patients with lung cancer who underwent surgical resection were included in the present study. Beclin-1 and Bcl-2 expression was assessed using immunohistochemistry and their associations with the overall survival (OS) in patients with NSCLC was examined. The expression rate of Beclin-1 was significantly lower in NSCLC tissues compared with that in adjacent tissues, whereas the expression rate of Bcl-2 was significantly higher in lung cancer tissues compared with that in adjacent tissues. Additionally, Beclin-1 and Bcl-2 protein expression was strongly associated (P<0.05) in NSCLC. Patients with NSCLC with low Beclin-1 expression were in more advanced stages, with more lymph node metastasis and more poorly differentiated tumors. Similarly, patients with NSCLC with high Bcl-2 expression were also in a more advanced stage and had more lymph node metastasis. Cox regression analysis revealed that the association between Bcl-2 expression and survival was not significant, while a multivariate analysis revealed that Beclin-1 expression was significantly associated with OS. Notably, Beclin-1 expression was significantly associated with OS only in patients with high Bcl-2 expression. In conclusion, the present data indicated that the autophagy activity is decreased in NSCLC. Beclin-1 expression was downregulated, while Bcl-2 expression was upregulated in NSCLC tissues compared with that in adjacent tissues. Additionally, these two proteins were associated with the occurrence and progression of NSCLC. Beclin-1 may be a promising prognostic marker for patients with NSCLC with high Bcl-2 expression. The present findings provided a more accurate prognostic assessment for patients with NSCLC. Furthermore, they may be used to actively follow-up and promptly treat patients with a poor prognosis, which may benefit a greater number of patients with NSCLC.

Methods for Dissecting Intersegmental Planes in Segmentectomy: A Randomized Controlled Trial.

BACKGROUND: The perioperative outcomes of the use of stapling devices versus electrocautery to dissect intersegmental planes in patients undergoing segmentectomy for small pulmonary lesions is still unclear. The aim of this randomized controlled trial was to compare the perioperative outcomes of these two methods. METHODS: A single-center, prospective, participant-blinded, randomized controlled trial (NCT03192904) was conducted with a preplanned sample size of 136. The primary outcome was the incidence of postoperative complications. Secondary outcomes included duration of operation, blood loss during operation, first-day drainage volume, duration of drainage, postoperative hospital stay, loss of lung function, and medical costs. RESULTS: The trial was stopped early as a result of a marked difference in the primary outcome between groups at a scheduled interim check of the data after recruiting 70 patients. The incidence of postoperative complications (eg, air leakage) was higher in the electrocautery group than in the stapler device group (11/32, 34.4% vs 2/33, 6.1%, P = .004). There were no differences in duration of operation, blood loss during operation, first-day drainage volume, duration of drainage, postoperative hospital stays, loss of lung function, or total medical cost, although the per-patient cost of medical materials was higher in the stapler device group (US$4214.6 ± 1185.4 vs $3260.1 ± 852.6, P < .001). CONCLUSIONS: Among patients undergoing segmentectomy, the use of stapler devices to divide intersegmental planes decreased postoperative complications without further compromising lung function or increasing economic burden.

Beclin-1 expression serves as an important biomarker for carcinogenesis and evolution in lung adenocarcinoma presenting as ground glass opacity.

BACKGROUND: The prognostic impact of Beclin-1 and relationship between Beclin-1 expression and carcinogenesis of lung adenocarcinoma has not been clarified. METHODS: The data of 10 patients with atypical adenomatoid hyperplasia (AAH), 20 patients with adenocarcinoma in situ (AIS), 28 patients with minimally invasive adenocarcinoma (MIA), and 50 patients with invasive adenocarcinoma (IA) who underwent surgical resection, were retrospectively reviewed. Normal lung tissues (NTs) were also collected for comparison. The expression levels of Beclin-1 mRNA and protein were detected by RT-PCR and western blotting, respectively. Immunohistochemistry was also performed. RESULTS: The transcriptional expression of Beclin-1 in lung adenocarcinoma presenting as GGO was significantly lower than that in NTs (P<0.05), and patients with MIA and IA showed a lower expression of Beclin-1 than that in patients with AAH and AIS (P<0.01). Lung adenocarcinomas with low expression of Beclin-1 were in more advanced stage (stage 0-I vs. stageII_III: 0.24±0.11 vs. 0.17±0.03, P<0.01), had more lymph node metastasis (P<0.01), and were of more invasive pathological subtype (P<0.01) than lung adenocarcinomas with high expression of Beclin-1. Low expression of Beclin-1 predicted worse survival in patients with IA (P<0.05). CONCLUSIONS: Beclin-1 expression was related with the evolution of lung adenocarcinoma. Beclin-1 may be an important marker for predicting the prognosis of patients with lung adenocarcinoma manifested as GGO.

Endoscope-assisted mediastinal drainage therapy for anastomosis leakage after esophagectomy: a retrospective cohort study.

BACKGROUND: Anastomosis leakage after esophagectomy is a major threat which leads to many subsequent complications even mortality. But current diagnosis and treatment methods are inefficient. This retrospective study aims to evaluate the utilization of endoscope-assisted mediastinal drainage therapy in treatment for anastomosis leakage after esophagectomy. METHODS: Between January 2014 and June 2018, 51 patients were confirmed anastomosis leakage using gastroscopy. Of them, 23 patients were treated with endoscope-assisted mediastinal drainage therapy (drainage group); and the other 28 patients received endoscope-assisted biomedical fibrin glue occlusion (occlusion group). Short-term clinical outcomes were examined. Factors related to length of postoperative hospitalization (LPH) was analyzed. RESULTS: Endoscope provided highly accurate information on the condition of anastomosis leakage. And there was no evidence that early endoscopy could cause damage to the anastomosis or gastric conduit. One patient from drainage group and two from occlusion group discharged against medical advice. Other 48 patients were completely cured without reoperation or mortality. The median LPH was 32 days in drainage group (range from 17 to 80 days) and 81 days in occlusion group (range from 32 to 190 days), respectively (P<0.05). Linear regression indicated statistically significant correlation between LPH and length from diagnosis to drainage or occlusion (R=0.688, P<0.001). CONCLUSIONS: Endoscope-assisted mediastinal drainage therapy is a satisfactory treatment for anastomosis leakage. Early diagnosis and treatment may facilitate the recovery of anastomosis leakage and reduce LPH.

Beclin 1 expression is associated with the occurrence and development of esophageal squamous cell carcinoma.

Beclin 1 has a central role in the regulation of autophagy, differentiation, apoptosis resistance, tumorigenesis and cancer progression. The role of Beclin 1 in the development of esophageal squamous cell carcinoma (ESCC) and its subsequent progression is not fully characterized. In the present study, the role of Beclin 1 and autophagy in ESCC was evaluated. The expression of Beclin 1 mRNA and protein levels in human ESCC tumor and adjacent normal esophageal tissue was measured. Beclin 1 mRNA and protein were significantly lower in tumor tissue than in normal esophageal tissue (P<0.05). Cells of the less differentiated esophageal tumors expressed lower Beclin 1 mRNA and protein (P<0.05). Tumors from patients in early clinical stages (I/II) exhibited significantly higher Beclin 1 mRNA and protein expression levels than patients with tumors in mid-to-late stages (III/IV; P<0.05). Tumors from patients with lymph node metastasis exhibited significantly lower Beclin 1 mRNA and protein expression levels compared with tumors from patients without lymph node involvement (P<0.05). Beclin 1 downregulation was demonstrated to significantly upregulate invasion by ESCC EC9706 cells (P<0.01), and downregulate the number of acidic vesicular organelles, a process associated with autophagy. These results suggest that the expression of Beclin 1 is associated with the occurrence and development of ESCC. Measuring the Beclin 1 expression of tumors from patient may improve the understanding of the prognosis of patients with ESCC.

Comparison of video-assisted thoracic surgery with open surgery in the treatment of ectopic mediastinal parathyroid tumors.

BACKGROUND: To investigate the therapeutic effect of different surgical treatment for ectopic mediastinal parathyroid tumors and pathological features. METHODS: A total of 21 patients who were diagnosed with ectopic mediastinal parathyroid tumors and underwent surgeries in our department from May 1995 to May 2015 were collected and retrospectively analyzed. RESULTS: Twenty-one patients including 8 female (36.4%) and 13 male (63.6%) were collected. Among these patients, 9 cases were treated with video-assisted thoracic surgery (VATS), while 13 cases were treated with open surgery (including one secondary open operation after thoracoscopic operation). The average size of mediastinal tumors was 2.17±1.22 cm. For the post-operational pathology, 16 cases (76.2%) were diagnosed as ectopic parathyroid adenoma; 4 cases (19.0%) were diagnosed as parathyroid hyperplasia, while only 1 case (4.8%) was diagnosed as parathyroid adenocarcinoma. CONCLUSIONS: Parathyroid adenoma accounts for the major pathological type of ectopic mediastinal parathyroid tumors. In addition, the correct diagnosis with precise preoperative location was the key for the treatment of ectopic mediastinal parathyroid tumors accompanied with hyperparathyroidism. Surgical intervention was demonstrated to be an effective way for the treatment of ectopic mediastinal parathyroid tumors with satisfied therapeutic outcome, especially for the VATS due to its unique clinical advantages. However, there may some difficulties when locating ectopic mediastinal parathyroid tumor less than 1 cm and the operators should be very cautious when performing thoracoscopic operations.

ATG7 deficiency promote apoptotic death induced by Cisplatin in human esophageal squamous cell carcinoma cells.

Cisplatin-(DDP)-based adjuvant chemotherapy is widely used for the treatment of esophageal cancer. However, DDP-based combinatorial treatments can eventually result in tumor resistance response. Therefore, new therapeutic strategies and/or new adjuvant drugs still need to be explored. In this study, we aimed to understand the role of autophagy in ESCC cells resistance to Cisplatin and discuss its potential therapeutic implication. We found that exposure to Cisplatin induced a significant increase in LC3 formation. While the proliferation of ESCC cells was inhibited upon Cisplatin exposure, inhibition of autophagy by ATG7 interference further increased the sensitivity to chemotherapy. Meanwhile, the Cisplatin-induced apoptotic cell death was significantly enhanced. These results suggest that autophagy may function importantly in ESCC cells resistance to Cisplatin. Intriguingly, the resistance could be recovered by autophagy inhibition. This also points to potential therapy for ESCC by perturbing autophagy.

The different induction mechanisms of growth arrest DNA damage inducible gene 45 ß in human hepatoma cell lines.

AIMS: Downregulation of the growth arrest and DNA damage-inducible gene 45 ß (GADD45ß) has been verified to be specific to HCC and consistent with the degree of malignancy. The differences in induction mechanisms of GADD45ß were investigated based on transcriptional regulation. METHODS: Following our published data from S-adenosylmethionine (SAMe), oxaliplatin and sorafenib were further used to stimulate GADD45ß expression in cultured HepG2 (p53 wild type) and Hep3B (p53 null) hepatoma cells in vitro. The different effects on cell viability, DNA synthesis and caspase activities were also measured. RESULTS: Oxaliplatin and sorafenib could induce GADD45ß in both HepG2 and Hep3B in a dose-dependent manner with rapid and direct cytotoxic effect. Transcriptional activity of NF-ĸB and E2F-1 were both enhanced by oxaliplatin and sorafenib. However, SAMe could only induce GADD45ß in HepG2 through the NF-ĸB pathway, resulting in a slow and indirect cytotoxic effect. Although all three inducers could lead to a pronounced rise in caspase activities, only high concentration of SAMe could inhibit DNA synthesis as significantly as the chemo drugs. No apparent changes in GADD45ß induction, promoter activity or cytotoxic effects were observed in Hep3B(+p53) when treated with oxaliplatin and sorafenib, while relatively significant changes occurred with SAMe. CONCLUSION: GADD45ß induction is a novel mechanism of SAMe-mediated hepatoprotection with p53 involvement.