A panel based on three-miRNAs as diagnostic biomarker for prostate cancer.

Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting the male life cycle. The incidence and mortality of prostate cancer are also increasing every year. Detection of MicroRNA expression in serum to diagnose prostate cancer and determine prognosis is a very promising non-invasive modality. Materials and method: A total of 224 study participants were included in our study, including 112 prostate cancer patients and 112 healthy adults. The experiment consisted of three main phases, namely, the screening phase, the testing phase, and the validation phase. The expression levels of serum miRNAs in patients and healthy adults were detected using quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic ability, specificity, and sensitivity of the candidate miRNAs. Result: Eventually, three miRNAs most relevant to prostate cancer diagnosis were selected, namely, miR-106b-5p, miR-129-1-3p and miR-381-3p. We used these three miRNAs to construct a diagnostic panel with very high diagnostic potential for prostate cancer, which had an AUC of 0.912 [95% confidence interval (CI): 0.858 to 0.950; p < 0.001; sensitivity = 91.67%; specificity = 79.76%]. In addition, the three target genes (DTNA, GJB1, and TRPC4) we searched for are also expected to be used for prostate cancer diagnosis and treatment in the future.

Testing the accuracy of a four serum microRNA panel for the detection of primary bladder cancer: a discovery and validation study.

BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.

Early detection and timely intervention can lead to a better prognosis of bladder cancer.This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer.

A three miRNAs panel in paraffin tissue serves as tool for predicting prognosis of renal cell carcinoma.

Background: Renal cell carcinoma (RCC) stands as the most prevalent form of urogenital cancer. However, there is currently no universally accepted method for predicting the prognosis of RCC. MiRNA holds great potential as a prognostic biomarker for RCC. Methods: A total of 100 cases with complete paraffin specimens and over 5-year follow-up data meeting the requirements were collected. Utilizing the clinical information and follow-up data of the specimens, an information model was developed. The expression levels of eight microRNAs were identified using RT-qPCR. Finally, determine and analyze the clinical application value of these microRNAs as prognostic markers for RCC. Results: Significant differences were observed in the expression of two types of miRNAs (miR-378a-5p, miR-23a-5p) in RCC tissue, and three types of miRNAs (miR-378a-5p, miR-642a-5p, miR-23a-5p) were found to be linked to the prognosis of RCC. Establish biomarker combinations of miR-378a-5p, miR-642a-5p, and miR-23a-5p to evaluate RCC prognosis. Conclusion: The combination of three microRNA groups (miR-378a-5p, miR-642a-5p, and miR-23a-5p) identified in paraffin section specimens of RCC in this study holds significant potential as biomarkers for assessing RCC prognosis.

PSMA1, a Poor Prognostic Factor, Promotes Tumor Growth in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC) has a poor clinical prognosis and lacks effective targeted therapy. This study is aimed at investigating the role of PSMA1 (proteasome subunit alpha type-1) in LUSC. The differential expression genes (DEGs) in LUSC were retrieved from The Cancer Genome Atlas (TCGA) by "edgR" algorithm and by "limma" R package. Then, the relationship between genes and overall survival (OS) was explored by the least absolute shrinkage and selection operator (LASSO) and multivariate Cox (multi-Cox) regression. Next, the PSMA1 expression in tissues of LUSC was detected by IHC, qRT-PCR, and western blot (WB). Moreover, the effects of PSMA1 on the proliferation and viability of LUSC cell were explored by cell counting kit 8 (CCK-8) assays, colony formation assays, and flow cytometry (FCM) analysis. All 4421 DEGs were screened by TCGA database, and 26 genes associated with OS were selected by multi-Cox. Based on TCGA database, PSMA1 was highly expressed in tissues of LUSC patients, and OS and FP of patients with PSMA1 overexpression were significantly lower than those of patients with low PSMA1 expression. Furthermore, PSMA1 knockdown significantly decreased the proliferation of LUSC cells and promoted the apoptosis of LUSC cells, and these effects were reversed by PSMA1 overexpression. The results of this project supported that PSMA1 might be a critical gene regulating the development of LUSC and has the potential to be explored as a prognostic biomarker of LUSC.

Clinical Efficacy of Thoracoscopic Surgery with the da Vinci Surgical System versus Video-Assisted Thoracoscopic Surgery for Lung Cancer.

Objective: To assess the clinical efficacy of thoracoscopic surgery with the da Vinci surgical system versus video-assisted thoracoscopic surgery (VATS) for lung cancer. Methods: From August 2019 to December 2020, 193 patients with lung cancer assessed for eligibility scheduled for surgery in our hospital were recruited and assigned at a ratio of 1 : 1 to receive VATS (control group) or thoracoscopic surgery with the da Vinci surgical system (research group). The primary measurement is the clinical efficacy of the two surgical modalities. Results: The baseline features of the research group were comparable with those of the control group (P > 0.05). Besides, the two groups showed similar tumor types, tumor locations, and clinicopathological staging (P > 0.05). Da Vinci surgical system-assisted thoracoscopic surgery had short operative time, less intraoperative blood loss, better lymph node dissection, and lower intraoperative conversion rates compared to VATS. Compared with the control group, the research group had significantly higher postoperative forced expiratory volume in one second (FEV1), forced vital capacity (FVC), maximal voluntary ventilation (MVV), the functional assessment of cancer therapy-general module (FACT-G) of the FACT-lung (FACT-L) Chinese version V4.0, lung cancer-specific module scores, and total scores (P < 0.05). The research group showed better postoperative drainage volume, shorter intubation duration, and length of hospital stay and a lower incidence of complications versus the control group (P < 0.05). The da Vinci surgical system reduced the probability of intraoperative mistakes and better ensured a safe and satisfactory surgery. Conclusion: The thoracoscopic surgery with the da Vinci surgical system better reduces intraoperative and postoperative bleeding, shortens drainage and intubation duration, enhances the lung function and survival quality of patients, and lowers the risk of surgical mistakes to ensure surgical safety versus VATS.

Comprehensive Analysis of the Immune and Prognostic Implication of MMP14 in Lung Cancer.

More and more studies have indicated an association between immune infiltration in lung cancer and clinical outcomes. Matrix metalloproteinase 14 (MMP14) has been reported to be dysregulated in many types of tumors and involved in the development and progression of tumors. However, its contribution to cancer immunity was rarely reported. In the study, we found that MMP14 expression was distinctly upregulated in lung cancer specimens compared with nontumor lung specimens. High MMP14 expression predicted a poor prognosis of lung squamous cell carcinoma (LUSC) patients. Increased MMP14 expressions were observed to be positively related to high immune infiltration levels in most of the immune cells. A pathway enrichment analysis of 32 MMP14-associated immunomodulators indicated the involvement of T cell receptor signaling pathway and Toll-like receptor signaling pathway. Based on MMP14-associated immunomodulators, we applied multivariate assays to construct multiple-gene risk prediction signatures. We observed that risk scores were independently associated with overall survival. These data highlighted that MMP14 was involved in tumor immunity, indicating that MMP14 could serve as a novel prognostic biomarker and therapeutic target for lung cancer. Our data suggest that the four genes identified in this study may serve as valuable biomarkers of lung cancer patient outcomes.

Dynamin 3 Inhibits the Proliferation of Non-small-Cell Lung Cancer Cells by Suppressing c-MET-GBR2-STAT3 Complex Formation.

Dynamin 3 (DNM3) has gained increased attention ever since its potential as a tumor suppressor was reported. However, its action in lung cancer (LC) is undefined. In this study, the role of DNM3 in LC development was investigated. DNM3 expression was found to be downregulated in tumors of patients with LC, especially those with metastasis. The DNM3 downregulation enhanced the proliferative and metastatic ability of LC cells, whereas its upregulation had the opposite effects. In vivo xenograft experiments confirmed that lung tumors with lower DNM3 expression had higher growth and metastatic abilities. Mechanistic studies revealed that DNM3 interacts with growth factor receptor-bound protein 2 (GBR2), thereby interrupting tyrosine-protein kinase Met (c-MET)-GBR2-signal transducer and activator of transcription 3 (STAT3) complex formation, which suppressed STAT3 activation. Therefore, the absence of DNM3 frees GBR2 to activate STAT3, which regulates the expression of genes related to LC proliferation and metastasis (e.g., cyclin D1 and Snail family transcriptional repressor 1). Additionally, the c-MET inhibitor crizotinib effectively suppressed LC cell proliferation and migration in vitro and in vivo, even with DNM3 depleted. Therefore, our study has demonstrated the antitumor effect of DNM3 in LC and suggests that the inhibition of c-MET might be a promising strategy for treating those LC patients with low DNM3 expression.

Noninvasive Bioluminescence Imaging of Matrix Metalloproteinase-14 Activity in Lung Cancer Using a Membrane-Bound Biosensor.

Matrix metalloproteinase-14 (MMP-14) plays a crucial role in the cancer migration and metastasis by guiding the extracellular matrix remodeling and cell motility. Despite increasing efforts have been taken to develop methodology for measuring MMP-14 expression, there is a lack of tools capable of monitoring the MMP-14 dynamic activity with high temporal and spatial resolution in living cells and animals. Here, we describe the design of Gaussia luciferase (Gluc)-based membrane-bound biosensor for efficient visualization of MMP-14 activity. The epidermal growth factor (EGF) induced significant luciferase changes in the biosensor-transfected lung cancer cells. Deletion of the transmembrane domain in the mutant biosensor or treatment with an MMP-14 inhibitor, tissue inhibitor of metalloproteinase-2 (TIMP-2), relieved the EGF-induced luciferase activation, suggesting that MMP-14 functions at the cell surface to result in luciferase changes. Moreover, utilizing this biosensor, the bioluminescence signals activated by MMP-14 enabled clear visualization of MMP-14-positive lung tumors in animal models. Our results indicated this biosensor is an effective probe for quantitatively monitoring proteolytic activities in live cells and mouse models. These findings offer the general design of biosensors as an adaptable tool for studying various membrane-anchored proteases in biological models.

Challenges Caused by Imported Cases Abroad for the Prevention and Control of COVID-19 in China.

Background: Overseas imported cases of COVID-19 continue to increase in China, so we conducted this study to review the epidemiological characteristics of these patients. Methods: From February 26 to April 4, 2020, the imported cases from abroad were enrolled in this study. The effect of prevention countermeasures in curbing the spread of COVID-19 was assessed in this study. Moreover, we defined incubation period and confirmed time as from the date of leaving the epicenter to date of symptom onset and date of final diagnosed, respectively, and the interval of symptom onset to final diagnosed time was defined as diagnostic time. Categorical variables were summarized as numbers and percentages, and the difference among the variables were analyzed. Results: For 670 cases imported from abroad, 555 were Chinese and 115 were foreigners. Apparently, confirmed cases had significantly decreased after China was compelled to temporarily suspend the entry of foreign passport holders with valid visas or residence permits; 6 days after implement of controlled measures, the daily new confirmed cases were reduced to 13 cases. Moreover, about 84.3% of patients (166/197) presented symptoms 1 week after leaving the epicenter, and notably seven patients (3.6%) had symptoms 2 weeks after leaving the epicenter. The median incubation period was 3.0 days (inter quartile range, 1.0 to 6.0), the 95th percentile was 11.6 days. Additionally, most of cases (92.9%) were detected positively of nucleic acid after symptom onset with 4 days, the median diagnostic time was 2.0 days (interquartile range, 1.0 to 3.0), and the 95th percentile of the distribution was 5.0 days. Finally, about 5.8% of patients were healthy carriers, and the median confirmed time of asymptomatic patients was 4.0 days (interquartile range, 2.0 to 9.0). The following variables might be associated with confirmed time: symptom type (P = 0.005), exported regions (P < 0.001), and symptom onset time (P < 0.001). Conclusions: The prevention countermeasures for imported cases implemented by the Chinese government played an indispensable role in curbing the spread of COVID-19; the time of departure from epicenter could provide an estimate of the incubation period; and a confirmed time, 2-week quarantine period might need to be prolonged, while asymptomatic patients should be closely monitored.

MR imaging of thymomas: a combined radiomics nomogram to predict histologic subtypes.

OBJECTIVES: Accurately predicting the WHO classification of thymomas is urgently needed to optimize individualized therapeutic strategies. We aimed to develop and validate a combined radiomics nomogram for personalized prediction of histologic subtypes in patients with thymomas. METHODS: A total of 182 thymoma patients were divided into training (n = 128) and test (n = 54) cohorts. Radiomics features were extracted from T2-weighted, T2-weighted fat suppression, and diffusion-weighted images to establish a radiomics signature in the training cohort. Multivariate logistic regression analysis was used to develop a combined radiomics nomogram that incorporated clinical, conventional MR imaging variables, apparent diffusion coefficient (ADC) value, and radiomics signature. The efficacy of clinical, conventional MR imaging, or ADC model was also evaluated respectively. The performances of different models were compared by receiver operating characteristic analysis and Delong test. The discrimination, calibration, and clinical usefulness of the combined radiomics nomogram were assessed. RESULTS: The radiomics signature, consisting of 14 features, achieved favorable predictive efficacy in differentiating low-risk from high-risk thymomas, outperforming clinical, conventional MR imaging, and ADC models. The combined radiomics nomogram incorporating tumor shape, ADC value, and radiomics signature yielded the best performance (training cohort: area under the curve [AUC] = 0.946, test cohort: AUC = 0.878). The calibration curve and decision curve analysis indicated the clinical utility of the combined radiomics nomogram. CONCLUSIONS: The radiomics signature is a useful tool that can be used to predict histologic subtypes of thymomas. The combined radiomics nomogram improved the individualized subtype prediction in patients with thymomas. KEY POINTS: • Fourteen robust features were selected to develop a radiomics signature for preoperative prediction of thymoma subtype. • MRI-based radiomics signature can differentiate low-risk thymomas from high-risk thymomas with favorable predictive efficacy compared with clinical, conventional MR imaging, and ADC models. • Combined radiomics nomogram based on tumor shape, ADC value, and radiomics signature could improve the individualized subtype prediction in patients with thymomas.

Evaluation of the Effect of Lymph Node Status on the Survival of Non-Small Cell Lung Cancer Patients With Brain Metastases: Applications of a Novel Grade Prognostic Assessment Score Model Involving N Stage.

BACKGROUND: Grade prognostic assessment (GPA) is widely used to evaluate the prognosis of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs). This study aimed to investigate whether lymph node status (LNS) could be included as one of the GPA variables for NSCLC with BMs. METHODS: Overall, 586 patients with NSCLC and BMs were retrospectively analyzed. Overall survival stratified by LNS was analyzed using the Kaplan-Meier method. Multivariate analysis was also performed to identify independent prognostic factors using the Cox proportional hazards progression model. In the updated GPA index, prognostic factors and criteria of GPA score were weighted by effect magnitude relative risk (RR) and statistical significance. RESULTS: In NSCLC patients with BMs, those with lymph node involvement had worse overall survival (mOS, 13.4 months vs. 25.9 months, P <0.001) than those without lymph node involvement. Multivariate analysis showed that LNS might be an independent prognostic factor (RR: 1.702, CI: 1.340-2.162, P <0.001). Finally, five prognostic factors including LNS, the age of the patient, Karnofsky performance status (KPS), the number of BMs, and extracranial metastases were enrolled in our novel GPA index. With the updated GPA index involving the N stage, survival analysis was also performed. Prognostic results were significantly different among these four subgroups (Class A vs. Class B, P=0.047; Class B vs. Class C, P<0.001; Class C vs. Class D, P=0.007). CONCLUSIONS: These results indicate that LNS might be an indispensable prognostic factor in NSCLC with BM. The novel GPA model involving the N stage could provide more reliable evidence to estimate the survival of NSCLC patients with BMs.

Epidemiological Characteristics and Clinical Outcomes of Coronavirus Disease Patients in Northwest China: High-Volume Research From Low Population Density Regions.

Background: Few studies have reported the transmission characteristics of coronavirus disease (COVID-19) in low-density populations. This study has therefore analyzed the epidemiological characteristics and clinical outcomes of COVID-19 patients in Northwestern China, an area with low population density. Methods: From January 21 to March 11, 2020, data from patients diagnosed with novel coronavirus pneumonia (NCP) in areas of Northwestern China with lower population densities were retrospectively analyzed. Certain variables were categorized as numbers and percentages, with the ratio between resident patients (no history of going out during the epidemic) and imported patients representing the contagiousness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for COVID-19. Hospitalization time was also calculated. Results: A total of 617 COVID-19 patients were reported in Northwestern China, and the morbidity and mortality rates of 0.000005 and 0.011, respectively. Further analysis showed that the morbidity was inversely proportional to population density and distance from Wuhan City. This study enrolled 473 confirmed cases; among these patients, there were 248 residents and 225 imported cases with a ratio of 1:1. The youngest and oldest patients were 1 and 94 years of age, respectively, with a median age of 42 years. Fifteen (3.2%) patients were children or infants. Two patients were pregnant, and one patient gave birth to a healthy baby with negative results during her disease course. About 17.3% of patients (82 cases) were healthy carriers without any symptoms during their disease course. One male patient (0.2%) had recurrence of a positive test result 4 days after discharge. The median hospitalization time was 16.0 days, ranging from 2.0 to 43.0 days. Further analysis showed that age (P = 0.03) and severity status (P < 0.001) were significantly correlated with hospitalization time. Conclusions: The morbidity and mortality rates of COVID-19 patients in the regions with a low population density were lower than those of the national average in China. All populations were susceptible to infection by SARS-CoV-2. Asymptomatic patients with positive results should be taken seriously, and the hospitalization time of patients is associated with their age and severity status.

Larynx-preserving limited resection with total thoracic esophagectomy and gastric pull-up reconstruction: A promising treatment for selected cervical esophageal squamous cell carcinoma.

BACKGROUND/AIMS: There is no consensus on treatment for cervical esophageal squamous cell carcinoma (ESCC). Our aim is to evaluate the feasibility and outcome of larynx-preserving limited resection with total thoracic esophagectomy and gastric pull-up reconstruction for the treatment of cervical ESCC without tumor involvement of the larynx and hypopharynx. MATERIALS AND METHODS: Retrospective analysis of patients with cervical ESCC who underwent R0 surgical resection from 2006 to 2011 in our center was performed. Kaplan-Meier method was used to calculate the survival time for patients. RESULTS: In total, 74 cervical ESCC patients were enrolled in the study. The mortality rate in 30 days was 8.1%, the total complication rate (at least one) was 47.3%, anastomosis leakage occurrence was 37.8%, mechanical ventilation ratewas12.2%, the rate of normal oral diet within 15 days was 71.6%, and the anastomosis recurrence rate in follow-up was 8.1%. Detailed analysis showed that the anastomosis leakage, pulmonary infection, laryngeal recurrent nerve injury, and chylothorax were the most common complications in surgical patients. Finally, the survival data showed that the median survival time was 31.83 months (95% CI=12.39-51.28 months) and the 3-year and 5-year survival rates were 49.1% and 35.5%, respectively. CONCLUSION: Larynx-preserving limited resection with total thoracic esophagectomy and gastric pull-up reconstruction might be a feasible and effective surgical alternative for the cervical ESCC patients whose tumor does not involve the larynx and hypopharynx.

Fistula formation between the arterial blood supply of pulmonary sequestration and the oesophagus accompanied by an intermittent haematemesis.

This study aimed to report the case of a patient diagnosed with pulmonary sequestration accompanied by an intermittent haematemesis as the initial and life-threatening symptom. Emergent surgical intervention finally confirmed a rare direct fistula formation between the arterial blood supply of pulmonary sequestration and the oesophagus, which led to intermittent upper gastrointestinal haemorrhage. To our knowledge, this is the first case reported with this kind of fistula formation.

PLGA-PTMC-Cultured Bone Mesenchymal Stem Cell Scaffold Enhances Cartilage Regeneration in Tissue-Engineered Tracheal Transplantation.

The treatment of long-segment tracheal defect requires the transplantation of effective tracheal substitute, and the tissue-engineered trachea (TET) has been proposed as an ideal tracheal substitute. The major cause of the failure of segmental tracheal defect reconstruction by TET is airway collapse caused by the chondromalacia of TET cartilage. The key to maintain the TET structure is the regeneration of chondrocytes in cartilage, which can secrete plenty of cartilage matrices. To address the problem of the chondromalacia of TET cartilage, this study proposed an improved strategy. We designed a new cell sheet scaffold using the poly(lactic-co-glycolic acid) (PLGA) and poly(trimethylene carbonate) (PTMC) to make a porous membrane for seeding cells, and used the PLGA-PTMC cell-scaffold to pack the decellularized allogeneic trachea to construct a new type of TET. The TET was then implanted in the subcutaneous tissue for vascularization for 2 weeks. Orthotopic transplantation was then performed after implantation. The efficiency of the TET we designed was analyzed by histological examination and biomechanical analyses 4 weeks after surgery. Four weeks after surgery, both the number of chondrocytes and the amount of cartilage matrix were significantly higher than those contained in the traditional stem-cell-based TET. Besides, the coefficient of stiffness of TET was significantly larger than the traditional TET. This study provided a promising approach for the long-term functional reconstruction of long-segment tracheal defect, and the TET we designed had potential application prospects in the field of TET reconstruction.

Gankyrin promotes epithelial-mesenchymal transition and metastasis in NSCLC through forming a closed circle with IL-6/ STAT3 and TGF-ß/SMAD3 signaling pathway.

Our previous research showed that Gankyrin was overexpressed in NSCLC and significantly associated with clinicopathologic features and poor prognosis. In this study, we will explore potential effect of Gankyrin on EMT and metastasis in NSCLC. The ectopic higher expression of Gankyrin markedly increased the migration and invasion in NSCLC cells. In contrast, silencing Gankyrin inhibit this aggressive behavior in NSCLC cells. Further study demonstrated that overexpression of Gankyrin could decrease E-cadherin expression and increase expression of Vimentin and Twist1 at mRNA and protein levels. These data indicated that Gankyrin could facilitate occurrence and development of EMT. Also IHC analysis showed that Gankyrin expression was negatively correlated with E-cadherin expression, while positively correlated with Vimentin and Twist1 expression in NSCLC tissues. The mechanism study finally suggested that the Gankyrin-driven EMT was partially due to IL-6/p-STAT3 and TGF-ß/p-SMAD3 pathways activation. Taken together, our data provided a novel mechanism of Gankyrin promoting EMT and metastasis in NSCLC through forming a closed circle with IL-6/p-STAT3 and TGF-ß/p-SMAD3 signaling pathway.

Assessment of epidermal growth factor receptor mutation/copy number and K-ras mutation in esophageal cancer.

BACKGROUND: The molecular status of epidermal growth factor receptor (EGFR) in esophageal cancer has not been well elucidated. The purpose of the study was to investigate the prevalence of EGFR and K-ras mutation, and EGFR gene copy number status as well as its association with clinicopathologic characteristics, and also to identify the prognostic value of EGFR gene copy number in esophageal cancer. METHODS: EGFR mutation in exon 19/exon 21 and K-ras mutation in codon 12/codon 13 were detected by real-time PCR method, while EGFR gene copy number status was analyzed by fluorescent in situ hybridization (FISH). EGFR gene amplification and high polysomy were defined as high EGFR gene copy number status (FISH-positive), and all else were defined as low EGFR gene copy number status (FISH-negative). The relationship between EGFR gene copy number status and clinicpathologic characteristics was analyzed. Kaplan-Meier method and Cox proportional hazards regression model were employed to evaluate the effects of EGFR gene copy number status on the patients' survival. RESULTS: A total of 57 esophageal squamous cell carcinoma (ESCC) patients and 9 esophageal adenocarcinoma (EADC) patients were enrolled in the study. EGFR mutation was identified in one patient who was diagnosed as ESCC with stage IIIC disease. K-ras mutation was identified in one patient who was diagnosed as EADC. In all, 34 of 66 (51.5%) samples were detected as FISH-positive, which includes 30 ESCC and 4 EADC tumor samples. The correlation analysis showed that FISH-positive was significantly associated with the tumor stage (P=0.019) and lymph node metastasis (P=0.005) in esophageal cancer patients, and FISH-positive was also significantly associated with the tumor stage (P=0.007) and lymph node metastasis (P=0.008) in ESCC patients. Cox regression analysis showed that high EGFR gene copy number was not a significant predictor of a poor outcome for esophageal cancer patients (P=0.251) or for ESCC patients (P=0.092), but esophageal cancer patients or ESCC patients with low EGFR gene copy number may have longer survival than those with high EGFR gene copy number according to the survival curve trends. CONCLUSIONS: The results indicated that EGFR or K-ras mutation was rare in esophageal cancer, but high EGFR gene copy number is frequent, and correlated with advanced pathologic stage and more number of the metastatic regional lymph nodes, especially in ESCC. In addition, high EGFR gene copy number is likely to have a deleterious effect on prognosis of esophageal cancer patients or ESCC patients, although no statistical significance was reached in the study.

Inhibiting CREPT reduces the proliferation and migration of non-small cell lung cancer cells by down-regulating cell cycle related protein.

It has been reported that CREPT acts as a highly expressed oncogene in a variety of tumors, affecting cyclin D1 signal pathways. However, the distribution and clinical significance of CREPT in NSCLC remains poorly understood. Our study focused on the role of CREPT on the regulation ofnon-small cell lung cancer (NSCLC). We found that CREPT mRNA and protein expression was significantly increased in NSCLC compared with adjacent lung tissues and was increased in various NSCLC cell lines compared with the normal human bronchial epithelial (HBE) cell line. siRNA-induced knockingdown of CREPT significantly inhibited the proliferation and migration of NSCLC cell lines by arresting cell cycle in S phase. Moreover, CREPT knocking down affected the expression of cell cycle proteins including c-mycand CDC25A. Finally, we found there were obvious correlations between CREPT with c-myc expression in histological type, differentiation, and pTNM stages of NSCLC (P<0.05, rs>0.3). Immunohistofluorescence studies demonstrated a co-localization phenomenon when CREPT and c-myc were expressed. Thus, we propose that CREPT may promote NSCLC cell growth and migration through the c-myc and CDC25A signaling molecules.

Correlation of EGFR Del 19 with Fn14/JAK/STAT signaling molecules in non-small cell lung cancer.

Previous research has shown that p-EGFR (particularly mutated EGFR) may activate fibroblast growth factor-inducible 14 (Fn14) expression in non-small cell lung cancer (NSCLC), and the JAK/STAT signaling pathway may participate in this process. Thus, in order to verify this hypothesis, correlations among the expression levels of EGFR Del 19, Fn14 and JAK/STAT were detected and analyzed. The expression and location of these molecules were assessed using IHC, immunohistofluorescence, RT-qPCR and western blotting. The differences and correlations in the expression of these molecules and clinical pathological characteristics were statistically analyzed using Mann-Whitney U, Kruskal­Wallis H and cross-table tests. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of EGFR Del 19 and Fn14 expression on survival. Data showed that EGFR Del 19, Fn14 and JAK1/STAT1 expression was significantly related with differentiation, pTNM stage and lymphatic metastasis (P<0.01) and there was a marked correlation of EGFR Del 19, Fn14 and JAK1/STAT1 expression with histological type, differentiation, pTNM stage of NSCLC (P<0.05; rs>0.3). Immunohistofluorescence showed that there was a co-localization phenomenon between EGFR Del 19 and Fn14 expression. NSCLC patients with higher EGFR Del 19/Fn14 expression had a significantly worse prognosis than those with lower EGFR Del 19/Fn14 expression (P=0.0155/P=0.001; log-rank test). The multivariate analysis indicated that Fn14 expression may be an independent prognostic factor in NSCLC with EGFR Del 19 [hazard ratio (HR), 0.326; P=0.042]. Therefore, our results indicate that EGFR Del 19 may promote Fn14 and JAK1/STAT1 expression in NSCLC and Fn14 may serve as a prognostic biomarker in NSCLC with EGFR Del 19.

The role of postoperative adjuvant chemotherapy for lymph node-positive esophageal squamous cell carcinoma: a propensity score matching analysis.

The prognosis of patients with lymph node-positive esophageal squamous cell carcinoma (ESCC) who primarily receive radical esophagectomy remains poor. In this study, we aimed to retrospectively investigate the role of postoperative adjuvant chemotherapy with docetaxel- or paclitaxel-based regimens in these patients. A total of 434 consecutive patients were included in this study who underwent radical esophagectomy and were pathologically confirmed to have lymph node-positive ESCC from January 2005 to December 2010 in our institution. Among these patients, 113 patients received postoperative adjuvant chemotherapy (Group SC), and 321 patients underwent surgery alone (Group S). Propensity score matching and multivariate analyses were used to compensate for differences in some baseline characteristics. After matching, Group SC had significantly longer median disease-free survival (DFS) than that in Group S (23.63 months vs. 16.70 months; p = 0.006); further subset analysis revealed that a benefit regarding DFS was only associated with patients with N1 stage and with tumor length <4.5 cm. The median overall survival (OS) was similar between the two groups (38.57 months for Group SC vs. 25.27 months for Group S; p = 0.05). Multivariate analysis showed that postoperative chemotherapy, length of the tumor, T status, and N category were significantly independent predictive factors of tumor recurrence (p < 0.05). Our data suggested that adjuvant chemotherapy with docetaxel- or paclitaxel-based regimens could significantly improve DFS for patients with N1 stage and tumor length <4.5 cm ESCC and that it could potentially prolong OS for patients with lymph node-positive ESCC after surgery, compared with surgery alone. These results warrant further confirmation in prospective, randomized trials.