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Background The prevalence of lung adenocarcinomas (LUADs) has dramatically increased in recent decades. Ferroptosis is a process of iron‐dependent regulatory cell death. It is still unclear whether the expression of ferroptosis‐related genes (FRGs) is involved in the pathogenesis and survival of patients with LUAD. Methods We retrieved LUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and used LASSO Cox regression analysis to select the gene signature suitable for modeling. The risk score was calculated according to the model, and the patients were divided into high‐ and low‐risk groups according to the median risk score. Functional enrichment analysis was carried out by this group, and a model for predicting clinical prognosis was established by combining this group with clinical factors. Results Gene set enrichment analysis (GSEA) and single‐sample gene set enrichment analysis (ssGSEA) analysis showed that there were several immune‐related pathways and immune infiltration differences between high‐ and low‐risk groups. A prognostic model integrating 10 ferroptosis‐related genes (FR‐DEGs), and clinical factors were constructed and validated in an external cohort. Conclusions The FR‐DEGs signature was related to immune infiltration, and a model based on FR‐DEGs and clinical factors was established to predict the prognosis of patients with LUAD., FR‐DEGs signature has a high correlation with the clinical characteristics and immune microenvironment of lung adenocarcinoma patients. The prognosis prediction model of LUAD patients based on FR‐DEGs and clinical characteristics can accurately predict the prognosis of lung adenocarcinoma patients.

Backgrounds The Gustave Roussy Immune score (GRIm-Score) emerges as a novel prognostic scoring system for patient selection in phase I trials testing targeted immunotherapy for advanced-stage cancer. We tried to assess potential prognostic roles of preoperative GRIm-Score in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy for stage I-II non-small-cell lung cancer (NSCLC) by propensity score-matching (PSM) analysis. Methods This PSM-based analysis was performed on our single-center prospectively-maintained database between January 2014 and October 2015. A Kaplan-Meier survival analysis using the log-rank test was used to distinguish differences in both overall survival (OS) and disease-free survival (DFS) between the patients stratified by preoperative GRIm-Score. Multivariable Cox-proportional hazards regression analysis and PSM analysis were both carried out to determine the final independent prognostic parameters. Results There were 405 patients with surgically resectable stage I-II NSCLC included. Both OS and DFS were significantly shortened along with each number increase in the GRIm-Score group, showing a step-wise fashion. Such strong correlations between preoperative GRIm-Score estimated by a modified 3-category risk scale and survival outcomes still remained validated after PSM analysis. In addition, this GRIm-Score held the superior discriminatory power for predicting both OS and DFS to the other peripheral blood biomarkers. Multivariable analyses on the entire cohort and the PSM cohort demonstrated that GRIm-Score based on a 3-category risk assessment scale could be independently predictive of both OS and DFS. Conclusions The GRIm-Score tool can also serve as an effective and noninvasive marker to optimize prognostic prediction for surgically resectable stage I-II NSCLC.

Background Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitudinal follow-up of cardiac injury, inflammation and coagulation markers in relation to disease severity and outcome. Methods We retrospectively assessed 2068 patients with laboratory-confirmed COVID-19 between January 29 and April 1, 2020 at Tongji Hospital in Wuhan, China. We defined cardiac injury as an increase in high sensitivity cardiac troponin-I (hs-cTnI) above the 99th of the upper reference limit. We explored the dynamics of elevation in hs-cTnI and the relationship with inflammation (interleukin [IL]-6, IL-8, IL-10, IL-2 receptor, tumor necrosis factor-α, C-reactive protein) and coagulation (d-dimer, fibrinogen, international normalized ratio) markers in non-critically ill versus critically ill patients longitudinally and further correlated these markers to survivors and non-survivors. Results Median age was 63 years (first to third quartile 51–70 years), 51.4% of whom were women. When compared to non-critically ill patients (N = 1592, 77.0%), critically ill (defined as requiring mechanical ventilation, in shock or multiorgan failure) patients (N = 476, 23.0%), had more frequent cardiac injury on admission (30.3% vs. 2.3%, p, Graphical abstract Unlabelled Image, Highlights • In COVID-19 patients increased levels of hs-cTnI beyond day 3 since admission portend a poor prognosis. • A consistent positive correlation of hs-cTnI with IL-6 and d-dimer could suggest nonspecific cytokine-mediated cardiotoxicity. • The risk for cardiac arrest and rhythm disturbances in patients with elevated hs-cTnI suggest an arrhythmogenic nature.

Aberrant expression of microRNAs may affect tumorigenesis and progression by regulating their target genes. This study aimed to construct a risk model for predicting the prognosis of patients with lung adenocarcinoma (LUAD) based on differentially expressed microRNA-regulated target genes. The miRNA sequencing data, RNA sequencing data, and patients’ LUAD clinical data were downloaded from the The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs and genes were screened out by combining differential analysis with LASSO regression analysis to further screen out miRNAs associated with patients’ prognosis, and target gene prediction was performed for these miRNAs using a target gene database. Overlapping gene screening was performed for target genes and differentially expressed genes. LASSO regression analysis and survival analysis were then used to identify key genes. Risk score equations for prognostic models were established using multifactorial COX regression analysis to construct survival prognostic models, and the accuracy of the models was evaluated using subject working characteristic curves. The groups were divided into high- and low-risk groups according to the median risk score, and the correlation with the clinicopathological characteristics of the patients was observed. A total of 123 up-regulated miRNAs and 22 down-regulated miRNAs were obtained in this study. Five prognosis-related miRNAs were screened using LASSO regression analysis and Kaplan-Meier method validation, and their target genes were screened with the overlap of differentially expressed genes before multifactorial COX analysis finally resulted in an 11-gene risk model for predicting patient prognosis. The area under the ROC curve proved that the model has high accuracy. The 11-gene risk-prediction model constructed in this study may be an effective predictor of prognosis.

Coronavirus disease 2019 (COVID-19) is a global pandemic which has caused numerous deaths worldwide. The present study investigated the roles of hypoproteinemia in the clinical outcome and liver dysfunction of COVID-19 patients. In this retrospective study, we extracted data from 2,623 clinically confirmed adult COVID-19 patients (>18 years old) between January 29, 2020 and March 6, 2020 in Tongji Hospital, Wuhan, China. The patients were divided into three groups—non-critically ill, critically ill, and death groups—in accordance with the Chinese Clinical Guideline for COVID-19. Serum albumin, low-density lipoproteins cholesterol (LDL-C), and high-density lipoproteins cholesterol (HDL-C) concentrations and inflammatory cytokines levels were measured and compared among these three groups. The median age of these 2,623 patients was 64 years old (interquartile range (IQR), 52–71). Among the patients enrolled in the study, 2,008 (76.6%) were diagnosed as non-critically ill and 615 (23.4%) were critically ill patients, including 383 (14.6%) critically ill survivors and 232 (8.8%) critically ill deaths in the hospital. Marked hypoalbuminemia occurred in 38.2%, 71.2%, and 82.4% patients in non-critically ill, critically ill, and death groups, respectively, on admission and 45.9%, 77.7%, and 95.6% of these three groups, respectively, during hospitalization. We also discovered that serum low-density lipoprotein (LDL) and HDL levels were significantly lower in critically ill and death groups compared to non-critically ill group. Meanwhile, the patients displayed dramatically elevated levels of serum inflammatory factors, while a markedly prolonged activated partial thromboplastin time (APTT) in critically ill patients reflected coagulopathy. This study suggests that COVID-19-induced cytokine storm causes hepatotoxicity and subsequently critical hypoalbuminemia, which are associated with exacerbation of disease-associated inflammatory responses and progression of the disease and ultimately leads to death for some critically ill patients. Electronic Supplementary Material Supplementary material is available for this article at 10.1007/s11427-020-1733-4 and is accessible for authorized users.

BACKGROUND We report this propensity score matching (PSM) analysis to assess prognostic roles of preoperative gamma-glutamyl transpeptidase to platelet ratio (GPR) in video-assisted thoracoscopic (VATS) lobectomy for stage I-II non-small-cell lung cancer (NSCLC). METHODS The PSM-based study conducted on our single-center prospectively collected database from January 2014 to August 2015 provided Kaplan-Meier survival analyses using the log-rank test to discriminate differences in overall survival (OS) and disease-free survival (DFS) between patients stratified by preoperative GPR. RESULTS Our study includes 379 patients diagnosed with operable primary stage I-II NSCLC. A GPR value at 0.16 was recognized as the optimal cutoff point for prognostic prediction. Both OS and DFS of patients with GPR ≥0.16 were significantly shortened when compared to those of patients with GPR

Emerging evidence has shown that circular RNAs (circRNAs) serve as a promising biomarker in different malignancies. Specifically, circ_001569 has been found to be upregulated in some types of human gastrointestinal cancer. In this study, we aimed to investigate clinical significances, diagnostic and prognostic values of circ_001569 in pancreatic cancer (PC), and identify its effects on the malignant behaviors of PC cells. The expression of circ_001569 was determined in 26 tissues samples and 97 plasma samples from PC patients by qRT-PCR. Relationship between circ_001569 expression and clinicopathological parameters was analyzed by Chi-square test. Diagnostic and prognostic values of circ_001569 were evaluated by ROC curves, Kaplan-Meier curves, and Cox regression analysis. The effects of circ_001569 on the proliferation, migration, invasion, and apoptosis of PC cells were assessed by MTT, wound healing, Transwell invasion assays, and flow cytometric analysis, respectively. Results showed that the expression of circ_001569 was upregulated in tissues and plasma of PC patients. High circ_001569 level was positively correlated with lymphatic metastasis, clinical stage, and venous invasion. Circ_001569 level was an independent prognostic indicator for overall survival rates of PC patients, and patients with high circ_001569 level had a poor prognosis. The AUC of circ_001569 was 0.716 (95% CI: 0.642-0.790) with a sensitivity and specificity of 62.76% and 74.29%, respectively. In vitro, circ_001569 silencing decreased cell proliferation, migration, and invasion, but promoted cell apoptosis of PC cells. Our data demonstrate that high circ_001569 level associates with tumor malignant behaviors, and may serve as a potential biomarker in the diagnosis and prognosis of PC.

PTEN/AKT signaling cascade is frequently activated in various cancers, including lung cancer. The downstream effector of this signaling cascade is poorly understood. β-Thymosin 10 (TMSB10) functions as an oncogene or tumor suppressors in cancers, whereas its significance in lung cancer remains unknown. In this study, we showed that the activation of PTEN/AKT signaling promoted the expression of TMSB10. Based on the TCGA database, TMSB10 was upregulated in lung cancer tissues and its overexpression was correlated with poor prognosis of lung cancer patients. Functional experiments demonstrated that TMSB10 knockdown suppressed, while its overexpression promoted the proliferation, growth, and migration of lung cancer cells. Apoptosis and epithelial-mesenchymal transition were also regulated by TMSB10. We therefore suggest that TMSB10 is a novel oncogene for lung cancer. Targeting TMSB10 may benefit lung cancer patients with activated PTEN/AKT signaling.

BACKGROUND Increasing evidence suggests that cancer-associated inflammation is associated with poorer outcomes. The neutrophil-to-lymphocyte ratio (NLR), considered as a systemic inflammation marker, is thought to predict prognoses in colorectal cancer. In this study, we explored the association between the NLR and prognoses following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). MATERIAL AND METHODS From February 2002 to December 2012, a group of 202 patients diagnosed with LARC and receiving neoadjuvant CRT followed by radical surgery was included in our retrospective study. The associations between the pre-CRT NLR and clinicopathological characteristics, as well as the predictive value of pre-CRT NLR against survival outcomes, were analyzed. RESULTS The average NLR was 2.7±1.5 (median 2.4, range 0.6-12.8). There were 63 (31.2%) patients with NLR ≥3.0, and 139 (68.8%) patients with NLR

Background and objective The aim of this study was to summarize the clinical characteristics and evaluate the management approaches of primary breast diffuse large B-cell lymphoma (DLBCL) in the era of rituximab. Patients and methods A total of 24 female patients with newly diagnosed primary breast DLBCL treated between April 2006 and May 2013 were analyzed retrospectively. Ten patients (41.7%) received rituximab. Results For the whole group, the median age was 50 years (range 24-69 years). All patients had the disease detected with a palpable mass. The estimated 5-year overall survival and progression-free survival (PFS) rates of all the patients were 78.9% and 79.2%, respectively. A nonstatistically significant increase in PFS and overall survival was observed when rituximab was administered (5-year PFS: 90% vs 71.4%, P=0.285; 5-year overall survival: 90% vs 71.4%, P=0.239). Conclusion Primary breast DLBCL appears to be a rare disease. Adding rituximab might improve survival in patients with primary breast DLBCL. Further prospective studies are needed to evaluate the role of rituximab for primary breast DLBCL.

Jialin Luo,* Caineng Cao,* Yuan Zhu, Peng Liu, Luying Liu, Ke Lu, Na Zhang, Ning Zhou Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, People’s Republic of China *These authors contributed equally to this work Background and objective: The objective of the study was to evaluate the efficiency of chemotherapy (CT) combined with high-dose extended-field radiotherapy (RT) in stage I extranodal nasal-type natural killer/T-cell lymphoma (NKTCL). Patients and methods: Between January 2001 and November 2010, 103 stage I extranodal nasal-type NKTCL patients were retrospectively analyzed. Of these patients, 75 patients were treated by RT plus CT and 28 patients were treated by RT alone. CT included cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or CHOP-like regimen. Results: The median follow-up time was 42.6 months (range, 7.4–126.7 months). For patients in the RT alone group, the 5-year estimated progression-free survival (PFS) and overall survival (OS) rates were 67.0% and 71.4%, respectively. For patients in the RT + CT group, the 5-year estimated PFS and OS rates were 69.0% and 63.7%, respectively. In multivariate analysis, CT was an independent factor for PFS. Conclusion: The doxorubicin-based CT combined with high-dose extended-field RT yielded promising outcomes for stage I extranodal nasal-type NKTCL, and CT was an independent factor for PFS. Keywords: natural killer/T-cell lymphoma, chemotherapy, radiotherapy, prognosis

Long non-coding RNAs (lncRNAs) are emerging as important modulators of cancer progression, among which prostate cancer-associated transcript 1 (PCAT1) has been shown to be an oncogene in several tumors. However, the clinical significance and biological function of PCAT1 in endometrial carcinoma (EC) remain unclear. In this study, we used 89 EC tissues and HEC-1B, Ishikawa, RL95-2 and AN3CA EC cell lines. We found elevated expression levels of PCAT1 in EC tissues and cell lines using reverse transcription qPCR (RT-qPCR). The prognostic value of PCAT1 was determined using Kaplan–Meier survival and Cox regression analysis. The results showed that higher PCAT1 expression was positively correlated with FIGO stage, myometrial invasion, lymph node metastasis, and a shorter overall survival. A series of functional assays showed that the knockdown of PCAT1 by small interfering RNA (siRNA) targeting PCAT1 (siPCAT1) suppressed cell proliferation, migration and invasion, but promoted apoptosis. Western blot analysis further showed that B-cell lymphoma 2 (Bcl-2), vimentin and N-cadherin were downregulated, but E-cadherin and Bcl-2-associated death promoter (Bad) were upregulated in PCAT1-silenced EC cells. Taken together, our results underscore the oncogenic role of PCAT1 in EC and show that PCAT1 may be a potential therapeutic target in EC treatment.

Background High-grade spindle cell sarcomas are a subtype of rare, undifferentiated pleomorphic sarcomas (UPSs) for which diagnosis is difficult and no specific treatment strategies have been established. The limited published data on UPSs suggest an aggressive clinical course, high rates of local recurrence and distant metastasis, and poor prognosis. Case presentation Here we present the unusual case of a 45-year-old male patient with a lumbosacral UPS extending into the sacrum. An initial diagnosis of a low-grade malignant spindle cell tumor was based on a tumor core biopsy. After complete extensive resection, the diagnosis of an UPS of the lumbosacral region was confirmed by excluding other types of cancers. Despite treatment with neoadjuvant radiotherapy, extensive resection, and adjuvant chemotherapy, the patient presented with multiple pulmonary metastases 3 months after surgery. The patient then began treatment with crizotinib at an oral dose of 450 mg per day, based on the detection of a LMNA-NTRK1 fusion gene in the tumor by next-generation sequencing. Over 18 months of follow-up through July 2018, the patient maintained a near-complete clinical response to crizotinib. Conclusions The LMNA-NTRK1 fusion was likely the molecular driver of tumorigenesis and metastasis in this patient, and the observed effectiveness of crizotinib treatment provides clinical validation of this molecular target. Molecular and cytogenetic evaluations are critical to accurate prognosis and treatment planning in cases of UPS, especially when treatment options are limited or otherwise exhausted. Molecularly targeted therapy of these rare but aggressive lesions represents a novel treatment option that may lead to fewer toxic side effects and better clinical outcomes. Electronic supplementary material The online version of this article (10.1186/s12885-018-4749-z) contains supplementary material, which is available to authorized users.

Xin-Ru Chen,1,* Jian-Zhong Liang,2,* Shu-Xiang Ma,1 Wen-Feng Fang,1 Ning-Ning Zhou,1 Hai Liao,1 De-Lan Li,1 Li-Kun Chen1 1Department of Medical Oncology, 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally tothis work Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC). However, the efficacy of consolidation chemotherapy (CCT) in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. Methods: This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC) who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. Results: Among the 177 patients, 72 (41%) received CCT and 105 (59%) did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031), whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118). The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level

Background Synaptojanin 2 Binding Protein (SYNJ2BP) is essential to cell proliferation. Previous studies show that SYNJ2BP participates in sprouting angiogenesis, which plays an important part in several abnormal conditions including cancer. However, the activity of SYNJ2BP in hepatocellular carcinoma (HCC) has not been elucidated yet. Methods Firstly, real-time PCR and western blotting (WB) were adopted to evaluate SYNJ2BP expressions in HCC tissues and HCC cell lines. Secondly, we did follow-up and prognostic study to explore the association of SYNJ2BP expression and HCC patients prognosis. Thirdly, we induced or silenced SYNJ2BP expression on selected HCC cell lines and explored the function of SYNJ2BP in vitro and in vivo. Lastly, we conducted Cignal Finder Cancer 10-Pathway Reporter Array in combination with loss- and gain-of-function assay to investigate potential mechanisms. Results Through various techniques we found that SYNJ2BP was decreased in HCC tissues and HCC cell lines. The subsequent analysis showed that low expression of SYNJ2BP was associated with tumor size, tumor nodule number, vascular invasion, TNM stage and BCLC stage, and was an independent risk factor for survival of HCC. Later, the in vitro experiments demonstrated that SYNJ2BP inhibited HCC cells invasion, migration and proliferation, also the in vivo testing revealed that SYNJ2BP inhibited tumor growth and metastasis. Finally, we also uncovered that SYNJ2BP inhibited HCC growth and metastasis through activating DLL4-mediated Notch signaling pathway. Conclusions Collectively, our data provide evidence that SYNJ2BP may act as a tumor suppressor during HCC development and could serve as a potential therapeutic target.

It has been reported that hsa‑microRNA (miRNA/miR)‑372 functions as a tumor suppressor or oncogene in various digestive system tumors, however, its roles in gallbladder cancer (GBC) are yet to be established. The present study aimed to determine the expression and clinical relevance of hsa‑miR‑372 in GBC. The expression of hsa‑miR‑372 in 80 pairs of human GBC tissues and adjacent normal gallbladder tissues was measured by reverse transcription‑quantitative polymerase chain reaction. Subsequently, the associations between hsa‑miR‑372 expression levels and the clinicopathological characteristics of patients with GBC were determined using χ2 test. Furthermore, Kaplan‑Meier method and Cox regression analysis were performed to evaluate the association between hsa‑miR‑372 expression and the prognosis of patients with GBC. Furthermore, a dual‑luciferase reporter assay and western blot analysis were performed to predict and verify the target gene of hsa‑miR‑372. The results demonstrated that markedly lower hsa‑miR‑372 expression was observed in GBC tissues, which was associated with poor prognosis in patients with GBC. Downregulated expression of hsa‑miR‑372 was negatively associated with tumor histological grade, tumor‑node‑metastasis stage, lymph node metastasis and distant metastasis, however, no association was observed between reduced hsa‑miR‑372 expression and patient gender, age, tumor size and gallbladder stones. Multivariate Cox regression analysis revealed that hsa‑miR‑372 expression, histological grade and lymph node metastasis were independent prognostic factors for overall survival in patients with GBC. Chloride intracellular channel 1 (CLIC1) was previously reported to be an effective biomarker for predicting the prognosis of GBC. Notably, the results of the present study indicated that CLIC1 may be a direct target gene of hsa‑miR‑372. In conclusion, the current study provides the first statistically convincing evidence that downregulation of hsa‑miR‑372 may occur in GBC tissues, which may be associated with aggressive and progressive tumor behavior by affecting CLIC1 expression.

To investigate the relationship between uridine diphosphate glucoronosyltransferase 1A1 (UGT1A1)*28/*6 and toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer (CRC) in Xinjiang Uygur and Han population. A total of 183 patients (Uygur, 114; Han, 69) with advanced CRC who received the irinotecan-based chemotherapy were enrolled in this retrospective analysis. Polymerase chain reaction amplification and direct sequencing method were used for UGT1A1*28 and UGT1A1*6 polymorphism detection. The patients were followed up to analyze the relationship between different genotypes with adverse reactions and the clinical outcome of irinotecan-based chemotherapy. Significant differences were found in genotype frequencies of UGT1A1*28 and UGT1A1*28/*6 between Uygur and Han (P = 0.02 and P = 0.002). Uygur and Han patients carrying wild UGT1A1*28 and *6 genotypes appeared to have significantly lower diarrhea incidence (I/II and III/IV) than those carrying mutant genotypes (all P

Background Overexpression of Metastasis-associated protein 1 (MTA1) in various cancer cells promotes tumor invasion and migration and predicts cancer patients’ poor prognosis. The pilot RNA-Seq data from our laboratory indicated that Epithelial cell adhesion molecule (EpCAM) was statistically reduced in MTA1-silencing cells. EpCAM has been recognized as more than a mere cell adhesion molecule and recent findings have revealed its causal role in mediating migratory and invasive capacity. Thus, this study was aimed to explore whether MTA1 was able to upregulate EpCAM expression and, consequently, modulate its effects on invasion and migration of the lung cancer cells as well as patients’ prognosis. Methods We checked the EpCAM expression by overexpressing or silencing MTA1 in lung cancer cells. Furthermore, these lung cancer cells with stably overexpressed or silenced MTA1 were transfected with siEpCAM or EpCAM-expressing plasmids and then subjected to western blot, invasion and migration assays. In addition, patients (n = 118) with early-stage lung cancer were enrolled in this study to confirm the correlations between MTA1 and EpCAM and pathoclinical parameters by using immunohistochemistry (IHC). All statistical analyses were performed with SPSS 20.0 statistical software. Results MTA1 upregulated EpCAM expression in lung cancer cell lines, and EpCAM overexpression rescued the inhibitory effects by silencing MTA1 on cell invasion and migration in vitro. What’s more, both MTA1 and EpCAM, correlated to each other, were overexpressed in lung cancer tissues and significantly correlated with their clinical stages, tumor diameters, lymph node metastasis. Multivariate analysis indicated that local advancement (p = 0.03), MTA1 overexpression (p = 0.001) and EpCAM overexpression (p = 0.045) of the lung cancer tissues remained significant in predicting unfavorable overall survival. Conclusions We revealed a new molecular mechanism of MTA1-mediated invasion and metastasis in lung cancer through downstream target EpCAM, and interfering with EpCAM function may be a novel therapeutic strategy for treatment of MTA1-overexpressing lung carcinoma.

Objective The aim of this study was to evaluate the clinical characteristics and survival outcomes of patients with primary mediastinal germ cell tumor (PMGCT) by identifying the prognostic factors and efficacies of different treatment modalities. Methods Fifty-five patients with PMGCT who were treated consecutively at Cancer Center, Sun Yat-sen University, Guangzhou, from 1988 to 2010 were evaluated retrospectively. Results Fifty-two men and 3 women with a median age of 25 years were identified, of whom 17 (30.9%) had pure seminomatous, 38 (69.1%) had nonseminomatous histology, 27 (49.1%) had tumor located at mediastinum, 20 (36.4%) had lung metastases and/or effusions, and 8 (14.5%) had distant metastases. Three treatments surgery, chemotherapy, and radiotherapy were performed in 11 (20%) patients, two treatments chemotherapy plus surgery or radiotherapy were performed in 25 (45.6%), and single treatment surgery or chemotherapy was performed in 17 (30.9%). The other two patients (3.6%) received no treatment. After a median follow-up time of 31.4 months, the 5-year survival rate was 52%. The median overall survival time was 87.9 months. Patients who received two treatments had the longest survival time of 118.3 months, P = 0.000. Those who had pure seminoma histology, whose tumor confined to the mediastinum and who achieved complete or partial remission at initial evaluation, who had complete resection and radiotherapy were considered to have better prognosis according to univariate analysis. On multivariate analysis, extension and response rate at initial evaluation were independently predictive of survival. Conclusions Primary mediastinal germ cell tumor is rare with a dominant frequency in young male patients. Chemotherapy combined with local therapy like surgery or radiotherapy is a reasonable treatment strategy recommended. Extension and initial remission rate are independent prognostic factors.

To retrospectively analyze the survival of renal cell carcinoma patients with bone metastases, evaluate the effect of treatment and identify the prognostic factors in these patients.A total of 66 renal cell carcinoma patients with bone metastases treated at our hospital between October 1990 and October 2010 were divided into 3 groups: solitary bone metastasis referred for radical surgery (n = 19); palliative surgery for solitary/multiple bone metastasis (n = 31); extraosseous metastasis without orthopedic surgery (n = 16). The effects of different variables on survival were determined according to the Kaplan-Meier method and Log-Rank test. And Cox proportional hazard regression model was used to estimate the prognostic factors.Their mean follow-up period was 25 (6-68) months. The survival significantly improved if bone metastases were solitary (45 vs 29 and 13 months, both P0.01), there was no vertebral bone involvement (31 vs 10 months, P0.01) and radical surgery was performed (50 vs 28 and 13 months, both P0.01). Age, gender, tumor size, alkaline phosphatase and lactate dehydrogenase had no effect on survival (all P0.05). Based on Cox regression analysis, survival was influenced by the number of metastasis foci (RR = 0.259, 95%CI:0.075-0.897) , type of procedure (RR = 17.845, 95%CI:4.246-74.992) and vertebral bone involvement (RR = 4.526, 95%CI:1.896-10.803) (all P0.05).Surgery is a better option for achieving local tumor control, providing good function and increasing the survival of patients with bone metastases. And radical resection is indicated for the patients with a solitary metastasis.

Background Maintenance chemotherapy is one strategy pursued in recent years with intent to break through the chemotherapy plateau for advanced non-small cell lung cancer (NSCLC). However, given the toxicity, platinum-based combinations are rarely given for this purpose. We carried out the present prospective study of triplet platinum-based combination sequential chemotherapy in advanced NSCLC to investigate if patients could tolerate and benefit from such intensive treatment. Methods From Dec 2003 to Dec 2007, 190 stage IIIB and IV NSCLC patients in Sun yat-sen University sequentially received the 3 platinum-based combination (TP- NP-GP) treatment (T: paclitaxol 175 mg/m2 d1; N: vinorelbine 25 mg/m2 d1 and 8; G: gemcitabine 1 g/m2 d1 and 8; P: cisplatin 20 mg/m2 d1-5; repeated every 3 weeks). Patients were followed up to at least 3 years to obtain survival data. Treatment toxicities and the quality of life (QOL) were assessed during the whole treatment. Results There were 187 patients evaluable. The TP, NP and GP response rates with sequential use were 42.8% (80/187), 41.1% (65/158) and 28.8% (21/73) respectively. Median survival time was 18.2 months and the 1, 2 and 3 year overall survival (OS) rates were 78.7%, 38.5% and 21.3%. Patients receiving>6 cycles of chemotherapy had significantly longer OS and TTP (MST 25.3 vs. 14.5 months, TTP 15.1 vs. 9.1 months). The QOL on the whole for the patients was improved after chemotherapy. Conclusions The sequential chemotherapy strategy with triplet platinum-based combination regimens can improve the survival outcome and the quality of life of advanced non-small cell lung cancer patients.

The ventriculoseptal defect (VSD) is the most common form of congenital heart disease and a leading noninfectious cause of infant mortality. Growing evidence demonstrates that genetic defects are associated with congenital VSD. Nevertheless, VSD is genetically heterogeneous, and the molecular basis for VSD in an overwhelming majority of patients remains unknown. In this study, the whole coding region of GATA5, a gene encoding a zinc finger transcription factor crucial for normal cardiogenesis, was sequenced in 120 unrelated patients with VSD. The available relatives of the patient harboring the identified mutation and 200 unrelated individuals used as controls were subsequently genotyped. The causative potential of a sequence variation was evaluated by MutationTaster, and the functional effect of the mutation was characterized using a luciferase reporter assay system. As a result, a novel heterozygous GATA5 mutation, p.L199V, was identified in a patient with VSD, which was absent in 400 control chromosomes. Genetic analysis of the mutation carrier’s available family members showed that the substitution co-segregated with VSD transmitted in an autosomal dominant pattern. The p.L199V variation was automatically predicted to be disease causing, and the functional analysis showed that the GATA5 p.L199V mutant protein was associated with significantly reduced transcriptional activation compared with its wild-type counterpart. To the best of the authors’ knowledge, this is the first report on the link of functionally compromised GATA5 to human VSD, suggesting potential implications for the early prophylaxis and personalized treatment of VSD.

Up-regulated gene 4 (URG4) has been demonstrated to be involved in progression of various human cancers. This study investigated the clinicopathological significance of URG4 in epithelial ovarian cancer (EOC). Immunohistochemistry was applied to investigate the expression of URG4 in ovarian tissues of 116 patients. The correlation of URG4 with proliferating cell nuclear antigen index (PCNA) was analyzed and the prognostic value of URG4 in patients was also investigated. Pearson Chi-square test, Spearman correlation coefficient, univariate analysis, multivariate analysis, and Kaplan–Meier method were adopted. The positive rate of URG4 in EOC was higher than that in borderline and benign tumors (P = 0.001). URG4 was positively correlated with PCNA (r = 0.86, P = 0.006). In addition, univariate analysis showed URG4 expression level, clinical stage, pathologic grade, lymphatic metastasis, chemotherapy, and ascites influenced survival time (all P

Published data on the association between mitogen-activated protein kinase kinase kinase 1 (MAP3K1) gene rs889312 polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of seven eligible articles including 26,015 cases and 33,962 controls based on the search criteria were involved in this meta-analysis. We observed that the MAP3K1 rs889312 polymorphism was significantly correlated with breast cancer risk from the fixed effects model when all studies were pooled into the meta-analysis (the allele contrast model: OR 1.09, 95% CI 1.07–1.12; the homozygote codominant: OR 1.22, 95% CI 1.15–1.29; the heterozygote codominant: OR 1.07, 95% CI 1.04–1.11; the dominant model: OR 1.10, 95% CI 1.06–1.13; the recessive model: OR 1.18, 95% CI 1.12–1.25). No significant association was found in the BRCA1 mutation carriers in all genetic models. When stratified by BRCA2 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (C vs. A: OR 1.12, 95% CI 1.01–1.23; CC vs. AA: OR 1.35, 95% CI 1.06–1.71; the recessive model: OR 1.31, 95% CI 1.05–1.65). There was no evidence for significant association between MAP3K1 rs889312 polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort for all comparison models. In conclusion, this meta-analysis suggests that the MAP3K1 rs889312 C allele is a low-penetrant risk factor for developing breast cancer, and there is limited evidence to indicate that MAP3K1 rs889312 polymorphism is associated with increased risk of breast cancer in BRCA1 mutation carriers.

AIM: The E-cadherin-catenin complex is important for cell-cell adhesion of epithelial cells. Impairment of one or more components of this complex is associated with poor differentiation and increased invasiveness of carcinomas. We evaluated the expression pattern of E-cadherin and β-catenin in gastric carcinoma and dysplasia and analyzed their relationship with tumor clinicopathological features and patient survival. METHODS: Immunohistochemical staining of E-cadherin and β-catenin was performed from paraffin specimens of 163 gastric carcinomas, 44 gastric mucosal dysplasia, and 25 intestinal metaplasia, 28 atrophic gastritis and 12 healthy controls. RESULTS: Normal membrane staining was observed in intestinal metaplasia, atrophic gastritis and control biopsy specimens for E-cadherin and β-catenin. 36% and 16% of gastric dysplasia were stained abnormally for E-cadherin and β-catenin respectively. Abnormal expression of E-cadherin and β-catenin was demonstrated in 46% and 44% of gastric carcinoma respectively. Abnormal expression of E-cadherin and β- catenin occurred more significantly in Borrmann III/IV than in Borrmann I/II type (P < 0.005, respectively). A significantly higher proportion of signet-ring, mucinous and tubular adenocarcinomas were abnormally expressed for E-cadherin and β-catenin as compared with papillary adenocarcinomas (χ2 = 8.47, P < 0.005, and χ2 = 7.05, P < 0.01, respectively). Morever, abnormal E-cadherin and β-catenin staining occurred more frequently in diffuse than in intestinal type of tumor (χ2 = 18.18 and 17.79, P < 0.005, respectively). There was a significant correlation between abnormal β-catenin expression and positive lymph node metastasis. A survival advantage was noted in tumors retaining normal membranous expression of β-catenin, independent of type, grade, or stage of the disease (P < 0.0005). CONCLUSION: Abnormal expression of the E-cadherin-catenin complex occurs frequently in gatric carcinoma, closely related to its histogenesis. Abnormal expression of the E-cadherin- catenin complex in gastric dysplasia may be an early event in the tumorigenesis. The close correlation with poor survival suggests that abnormal β-catenin may be a useful prognostic marker.