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Our study aimed to elucidate the function of IMP U3 small nucleolar ribonucleoprotein 4 (IMP4) in lung adenocarcinoma (LUAD) and its potential molecular mechanisms. Cell counting kit-8, 5-ethynyl-20-deoxyuridine, flow cytometry, wound healing, and transwell assays were performed to examine the biological behaviour of LUAD cells. mRNA and protein expression levels were determined using quantitative real-time PCR, Western blotting, and immunohistochemistry. In addition, a mouse tumour xenograft model was used to evaluate the role of IMP4 in tumour progression. Furthermore, glycolysis-related indicators were measured. The levels of IMP4 were up-regulated in both human LUAD tissues and cells. IMP4 silencing significantly suppressed proliferation, migration, invasion, and glycolysis; promoted apoptosis; and induced cell cycle arrest in LUAD cells. IMP4 silencing also inactivated the extracellular signal-regulated kinase (ERK) pathway. Moreover, rescue experiments demonstrated that the function of LUAD cells induced by IMP4 overexpression could be reversed by treatment with an ERK pathway inhibitor (SCH772984). In vivo experiments further verified that IMP4 silencing repressed the growth of subcutaneous tumours and glycolysis. IMP4 silencing suppressed the malignancy of LUAD by inactivating ERK signalling.

Background: We aimed at investigation of the effect and the underlying neurotrophin signaling pathway of the upstream transcription factor 1 (USF1) in lung adenocarcinoma (LUAD).Methods: The Cancer Genome Atlas (TCGA) database was used to analyze USF1 expression data and to extract patients’ clinical records. Immunohistochemical assay and Western blotting (WB) were used to determine the expression levels of USF1 in LUAD. The neurotrophin signaling pathway was analyzed by bioinformatic analysis while the expression of all related proteins was determined by WB. In addition cellular viability, proliferation, migration and invasion potential were investigated by the CCK-8, colony formation, wound healing and transwell. Meanwhile, the effect of USF1 in LUAD progression was investigated in a mouse model. The link between USF1 and UGT1A3 (UDP Glucuronosyltransferase Family 1 Member A3) was studied by the dual-luciferase reporter assay. Results: We have detected a high expression level of USF1 in LUAD, which was associated with advanced tumor stage, nodal metastasis, and poor patient’s survival rate. The knockdown of USF1 inhibited cellular viability, proliferation, migration and invasion. Meanwhile, USF1 knockdown inhibited tumor growth in a mouse model. Besides, USF1 targeted UGT1A3, which was proven by the fact that the USF1 knockdown decreased the expression level of UGT1A3, whereas the upregulated expression of UGT1A3 increased cellular viability and proliferation. We have proved that the neurotrophin signaling pathway in LUAD was activated by USF1 and UGT1A3. The expression of the related proteins was also inhibited by the USF1 knockdown, while the overexpression of IRAK increased cancer cells’ migration and invasion potential.Conclusion: USF1 was highly expressed in LUAD and promoted LUAD progression by regulating the neurotrophin signaling pathway. These findings provide a new theoretical data that could serve as a good foundation for the treatment of LUAD.

Purpose: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is classified as non-small-cell lung cancer, but has characteristics similar to small-cell lung cancer. This study was performed to evaluate the effect of surgery and radiotherapy on patients with LCNEC. Materials and Methods: We analyzed 1,619 patients with stage I-III LCNEC, identified from the Surveillance, Epidemiology, and End Results database, diagnosed from 2000 to 2013. The Kaplan-Meier analysis and the Cox proportional hazard model were used to study patient prognosis. Results: Overall, 869 (53.7%) stage I LCNEC patients, 203 (12.5%) stage II patients, and 547 (33.8%) stage III patients were included in the analysis. Various surgery types were all associated with higher overall survival (OS) and lung cancer-specific survival (LCSS) than no surgery, with the following HRs: 0.334 (OS) and 0.279 (LCSS) for lobectomy, 0.468 (OS) and 0.416 (LCSS) for partial/wedge/segmental resection, and 0.593 (OS) and 0.522 (LCSS) for pneumonectomy (all p < 0.05). OS and LCSS of stage I and II LCNEC patients were not improved by radiotherapy (stage I: OS p = 0.719, LCSS p = 0.557; stage II: OS p = 0.136, LCSS p = 0.697). However, in stage III patients, radiotherapy significantly improved both OS and LCSS (p < 0.001). Following multivariate analysis, increased age, male patients, radiotherapy and diagnosed at stage II or III were all independent risk factors for LCNEC (all p < 0.05). Conclusion: Lobectomy had the best outcome for OS and LCSS in stage I-II LCNEC. For stage III LCNEC patients, radiotherapy can significantly improve survival time. However, in LCNEC patients undergoing surgery, radiotherapy may reduce survival time.

BackgroundClinically, there are no clear guidelines on the extent of lymphadenectomy in patients with T1 esophageal cancer. Studying the minimum number of lymph nodes for resection may increase cancer-specific survival.MethodsPatients who underwent esophagectomy and lymphadenectomy at T1 stage were selected from the Surveillance, Epidemiology and End Results Program (United States, 1998–2014). Maximally selected rank and Cox proportional hazard models were used to examine three variables: the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio.ResultsApproximately 18% had lymph node metastases, where the median values were 10, 10 and 0 for the number of lymph nodes examined, the number of negative lymph nodes and the lymph node ratio, respectively. All three examined variables were statistically associated with cancer-specific survival probability. Dividing patients into two groups shows a clear difference in cancer-specific survival compared to four or five groups for all three variables: there was a 29% decrease in the risk of death with the number of lymph nodes examined ≥14 vs 0.05 vs ≤ 0.05.ConclusionsThe extent of lymph node dissection is associated with cancer-specific survival, and the minimum number of lymph nodes that need to be removed is 14. The number of negative lymph nodes and the lymph node ratio also have prognostic value after lymphadenectomy among T1 stage patients.

Background: In clinical work, it is increasingly finding that even for patients with the same TNM stage of esophageal cancer (EC), the prognosis of different patients is still very different. Tumor length has been analyzed as a possible independent prognostic factor in many studies, but no unanimous conclusion has been reached. Therefore, this review is expected to use meta-analysis to evaluate the association between tumor length and prognostic significance in EC patients.Methods: A systematic search for relevant articles was performed in the PubMed, Web of Science, and Embase. Hazard ratio and 95% confidence intervals (CIs) will be used as effective measures to estimate the correlation between tumor length and prognostic significance including overall survival, disease-free survival, progression-free survival, disease-specific survival, and cancer-specific survival. We will use the software STATA 15.0 to perform the meta-analysis to calculate the data synthesis. Results: Finally, 41 articles with 28, 973 patients were included in our study. Comprehensive statistical results showed that long tumor is an independent prognostic parameter associated with poor overall survival (OS) (HR=1.30; 95%CI: 1.21-1.40, ppConclusion: The results of this meta-analysis showed that the long tumor was related to the poor OS, DFS, PFS, DSS and CSS in EC patients. It was suggested that tumor length might be an important predictor of prognosis in EC patients，and it can be used as an independent staging index. Further well-designed and large-scale prospective clinical studies are needed to confirm these findings.

OBJECTIVES Lung cancer is the leading cause of cancer-related death worldwide. The 5-year survival rate for patients after curative surgery with pathological N0 non-small-cell lung cancer (NSCLC) is as low as 56%, which is due to recurrence and metastasis. Emerging evidence suggests that epithelial-mesenchymal transition is important for cancer metastasis. Twist and Snail are epithelial-mesenchymal transition regulators that induce metastasis by down-regulating E-cadherin. The aim of this study was to evaluate the prognostic value of Twist, Snail and E-cadherin expression in patients with resectable pathological N0 NSCLC. METHODS The expression levels of Twist, Snail and E-cadherin in 78 patients with resected pathological N0 NSCLC were assessed using immunohistochemistry. The association between the expression of Twist/Snail/E-cadherin and overall survival (OS) and recurrence-free survival (RFS) was investigated. RESULTS High expression of Twist, Snail and E-cadherin was detected in 18%, 21% and 53% of NSCLC samples, respectively. High expression of Twist and Snail and low expression of E-cadherin were associated with worse RFS [hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.07-4.87, P = 0.026; HR 2.54, 95% CI 1.24-5.20, P = 0.008 and HR 2.41, 95% CI 1.23-4.73, P = 0.007, respectively] and worse OS (HR 2.26, 95% CI 1.01-5.04, P = 0.040; HR 2.56, 95% CI 1.20-5.43, P = 0.011 and HR 2.42, 95% CI 1.18-4.95, P = 0.012, respectively). Co-expression of at least 2 markers from the combination of high Twist/high Snail/low E-cadherin expression predicted poor RFS and OS (HR 4.12, 95% CI 2.08-8.16, P

Objectives: Chemotherapy and radiation therapy are the standard treatments for patients with small-cell lung cancer (SCLC). However, recent studies suggest that patients with limited stage (I-III) SCLC may benefit from surgical treatment. This study was performed to evaluate the survival outcomes of surgery for stage I-III SCLC. Methods: This analysis used data from the Surveillance, Epidemiology, and End Results (SEER) database. All stage I-III (excluding N3 and Nx) SCLC patients received a diagnosis between 2004 and 2014. Overall survival (OS) and lung cancer-specific survival (LCSS) were determined by Kaplan-Meier analysis and compared using the log-rank test. A Cox proportional hazard model identified relevant survival variables. Results: A total of 4,780 histologically confirmed patients were identified from the SEER database, comprising 1,018 patients (21.3%) with stage I disease; 295 (6.2%) with stage II; and 3,467 (72.5%) with stage III disease. Among all of the patients, 520 had been treated with surgery, the majority (n = 344; 66.2%) of whom had stage I disease. The hazard ratio (HR) for OS and LCSS, in patients who underwent surgery, according to stage were as follows: OS, 0.369 and LCSS, 0.335 in stage I; OS, 0.549 and LCSS, 0.506 in stage II; and OS, 0.477 and LCSS, 0.456 in stage III (all p < 0.001). Patients who underwent surgery had significantly better OS, and lobectomy was associated with the best outcome. Conclusions: Surgical resection was associated with significantly improved OS outcomes and should be considered in the management of stage I-III SCLC.

Background: More and more studies were performed to explore the prognostic role of tumor length in esophageal cancer (EC). However, the results remain controversial. Hence, the aim of the review was to evaluate the association between tumor length and oncologic outcome in EC patients through meta-analysis. Methods: A systematic literature search for relevant articles published in English language will be conducted in the PubMed, Web of Science, and Embase. Hazard ratio and 95% confidence intervals (CIs) will be employed as effect measures to estimate the correlation between tumor length and the oncologic outcomes including overall survival, disease-free survival, progression-free survival, relapse-free survival, and cancer-specific survival. We will use the software STATA 14.0 to perform the meta-analysis to calculate the data synthesis. Results: The review will provide a high-quality synthesis of current evidence of the prognostic role of tumor length in ECs. The results will be published in a peer-reviewed journal. Conclusion: This will be the first systematic review and meta-analysis to evaluate the prognostic role of tumor length in EC patients. The results will better predict EC survival and identify higher-risk patients for postoperative therapy. PROSPERO registration number: This systematic review protocol has been registered in the PROSPERO network (No. CRD42018106851).

Background The current TNM classification system does not consider tumor length for patients with esophageal carcinoma (EC). This study explored the effect of tumor length, in addition to tumor depth and lymph node involvement, on survival in patients with esophageal squamous cell carcinoma (ESCC). Methods A total of 498 ESCC patients who underwent surgical resection as the primary treatment were selected in the retrospective study. Pathological details were collected, which included tumor type, TNM stage, differentiation. Other collected information were: the types of esophageal resection, ABO blood group, family history and demographic and lifestyle factors. A time-dependent receiver operating characteristic (ROC) curve and a regression tree for survival were used to identify the cut-off point of tumor length, which was 3 cm. Univariate and multivariate Cox proportional hazard regression models were used to identify the prognostic factors to ESCC. Results & Discussion The 1-, 3-, 5-year overall survival rates were found to be 82.5%, 55.6%, and 35.1%, respectively. Patients who had larger tumor length (>3 cm) had a higher risk for death than the rest patients. From the univariate Cox proportional hazards regression model, the overall survival rate was significantly influenced by the depth of the tumor and lymph node involvement (either as dummy or continuous variables), Sex, and tumor length. Using these four variables in the multivariate Cox proportional hazard regression model, we found that the overall survival was significantly influenced by all variables except Sex. Therefore, in addition to the depth of the tumor and lymph node involvement (as either dummy or continuous variables), the tumor length is also an independent prognostic factor for ESCC. The overall survival rate was higher in a group with smaller tumor length (≤3 cm) than those patients with larger tumor length (>3 cm), no matter what the tumor stage was. Conclusion The tumor length was found to be an important prognostic factor for ESCC patients without receiving neoadjuvant therapy. The modification of EC staging system may consider tumor length to better predict ESCC survival and identify higher risk patients for postoperative therapy.

Thoracic aortic dissection (TAD) is a life-threatening vascular condition, in which matrix metalloproteinases (MMPs) are involved. Since the key determinants underlying MMP action remain elusive, the present study investigated the correlation between single nucleotide polymorphisms (SNPs) in the promoter region of the MMP‑8 gene and a predisposition to TAD, by comparing genotypes of TAD patients and healthy controls. From 154 TAD patients and 148 healthy individuals, DNA samples were obtained from venous blood, and genotyping was performed by a combination of polymerase chain reaction and automatic sequencing to detect SNPs in the MMP‑8 promoter. Data were analyzed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. P

Introduction The pathogenesis of lung cancer is unclear. Less expression of p53 or p53 mutation was identified in lung cancer cells, which plays a role in the development of lung cancer. Recent reports indicate that Bcl2-like protein-12 (Bcl2L12) can inhibit the expression of p53. Lung cancer cells express proteinase-activated receptor-2 (PAR2). This study tests the hypothesis that activation of PAR2 inhibits the expression of p53 in lung cancer cells. Material and methods Lung cancer cells were collected from patients with non-small cell lung cancer (NSCLC). The cells were exposed to active peptides or trypsin in the culture for 48 h. The expression of p53 was assessed by RT-qPCR and Western blotting. Results We observed that lung cancer cells express Bcl2L12. Activation of PAR2 increases expression of Bcl2L12 in lung cancer cells. Bcl2L12 mediates PAR2-suppressed p53 expression in lung cancer cells. IgE-activated mast cell suppression of p53 expression in lung cancer cells can be prevented by knocking down Bcl2L12. The Bcl2L12 bound Mdm2, the transcription factor of p53, to prevent the Mdm2 from binding to the promoter of p53 and thus inhibited p53 expression in lung cancer cells. PAR2 could attenuate lung cancer cell apoptosis via inducing Bcl2L12. Conclusions Lung cancer cells express Bcl2L12, which mediates the effects of activation of PAR2 on suppressing the expression of p53 in lung cancer cells, implying that Bcl2L12 may be a novel therapeutic target for the treatment of lung cancer.

Background Many studies have been conducted to compare the hand-sewn and mechanical staples in esophageal cancer (EC) patients who received esophagogastric anastomosis. However, the results remain controversial. Hence, the purpose of the meta-analysis is to evaluate the impact of different anastomosis methods on the early and long-term outcomes. Methods We will perform a systematic electronic search of the PubMed, Embase, Cochrane Library, Web of Science for relevant articles published in English language. Pooled odds ratios will be calculated for the effect on discrete variables including anastomotic leakage, anastomotic strictures, 30-day mortality, quality of life, cardiac and pulmonary complications. The weighted mean difference was calculated for the effect size on continuous variables such as operative time and bleeding amount. We will use the software Review Manager 5.3 and STATA 14.0 to perform the meta-analysis to calculate the data synthesis. Results The review will provide a high-quality synthesis of current evidence of the impact of different anastomosis methods on postoperative course in ECs after esophagectomy. The results will be published in a peer-reviewed journal. Conclusion This systematic review and meta-analysis will compare the different anastomosis methods in EC patients. The results will better offer some specific suggestions for esophagogastric anastomosis. Prospero registration number This systematic review protocol has been registered in the PROSPERO network (No. CRD 42019109523).

Objective: The objective of this study was to compare the completely thoracoscopic anatomic segmentectomy with lobectomy to treat stage I A peripheral lung cancer 0.05). The local recurrence rate was not significant different in two groups (P > 0.05). Two groups of operative time, blood loss and number of dissected lymph nodes was not statistically significant (P > 0.05), However, the difference was statistically significant in average chest drainage and less decreased pulmonary function, which led to patients received segmentectomy recovered faster and hospitalized less time (P < 0.05). We also found there was no significant difference on survival rate with 1 and 3 year follow-up of two groups (log-rank Chi-square = 0.028, P > 0.05). Conclusions: For stage I A peripheral lung cancer, the thoracoscopic anatomic segmentectomy was safe and effective just as thoracoscopic lobectomy, and furthermore with faster post-operative recovery.

Background and aims: Synchronous liver metastasis (SLM) remains a significant problem in newly diagnosed colorectal cancer (CRC). The system of hepatocyte growth factor (HGF) and Met plays an important role in cancer invasion and metastasis and is being developed to be targeted drugs. We aimed to investigate the role of HGF/Met in SLM based on a case-matched study and comparison between primary tumors and matched metastases. Methods: A group of 30 patients with SLM and other two groups of patients without SLM in a hospital database were collected. They were matched into according to clinicopathological factors. 81 patients were included in the study. Their tissues of primary colorectal cancers, lymph nodes and liver metastases were collected to detect HGF and Met expression by immunohistochemistry and RT-PCR. Results: Expression of HGF and Met at the protein level and the RNA level in primary CRCs with SLM were significantly higher than that in primary colorectal carcinomas without liver metastases (all P value0.05). Comparison their expression between primary tumors and matched metastases, major concordance and minor difference existed. Conclusions: HGF and Met may exert functions in the development of SLM when concurrent with lymph node metastases but had little influence on SLM without lymph node metastasis, further indicating their roles and potential values for a subtype of colorectal cancer metastasis. Major concordance and minor difference exist between primary tumors and matched metastases, which further provides evidence for evaluating the response to their inhibitors based on primary tumors or metastases.

The prognostic significance of serum human epididymis protein 4 (HE4) levels in human NSCLC among a Chinese population has not been investigated. The purpose of this study was to evaluate the prognostic significance of serum HE4 level in patients with NSCLC among a Chinese population. Serum HE4 expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The overall survival (OS) analyzed by log-rank test, and survival curves was plotted according to Kaplan-Meier. The COX proportional hazards regression model was used to determine the joint effects of several variables on survival. Serum HE4 level was found to be significantly higher in patients with NSCLC than that of controls (13.76 ± 5.01 ng/ml vs. 5.09 ± 1.25 ng/ml, P < 0.01). High HE4 expression was correlated with TNM stage (P = 0.003), lymph node metastases (P = 0.007), and distant metastases (P < 0.001). Furthermore, patients with high serum HE4 level had a significantly lower 5-year OS rate (34.0% vs. 59.7%; P = 0.022) than those with low serum HE4 level. In a multivariate Cox model, we found that HE4 expression was an independent poor prognostic factor for 5-year OS (hazards ratio [HR] = 3.654, 95% confidence interval [CI] = 2.753-11.981, P = 0.019) in NSCLC. In conclusion, the detection of HE4 levels in the serum might serve as a new tumor biomarker in the prognosis of NSCLC among Chinese population.

Background The aims of this study were to investigate whether the preoperative hematologic markers, the neutrophil-lymphocyte ratio (NLR) or the platelet-lymphocyte ratio (PLR) were prognostic indicators and to develop a novel risk stratification model in pN0 non-small-cell lung cancer (NSCLC). Methods We performed a retrospective analysis of 400 consecutive pN0 NSCLC patients. Prognostic values were evaluated by Cox proportional hazard model analyses and patients were stratified according to relative risks for patients’ survival. Results During the follow-up, 117 patients had cancer recurrence, and 86 patients died. In univariate analysis, age, gender, smoke status and tumor size as well as WBC, NEU, LYM, PLR and NLR were significantly associated with patients’ prognosis. In multivariate analysis, age, tumor size and NLR were independent predictors for patients’ overall survival (P = 0.024, 0.001, and 0.002 respectively). PLR didn’t associated with patients’ survival in multivariate analysis. Patients were stratified into 3 risk groups and the differences among the groups were significant according to disease free survival and overall survival (P = 0.000 and 0.000 respectively). Conclusions We confirmed that NLR other than PLR was an independent prognostic factor. Combination of NLR, age and tumor size could stratify pN0 NSCLC patients into 3 risk groups and enabled us to develop a novel risk stratification model.