Prostate cancer (PCa) is the leading cause of cancer-related death among men worldwide. Knowledge of the prognostic factors of PCa and the bone metastasis pattern of patients would be helpful for patients and doctors. The data of 177,255 patients with prostate cancer diagnosed between 2010 and 2013 with at least five years of follow-up were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox regression analysis was used to determine the predictive value of patients’ characteristics for survival after adjusting for other variates. Multivariate logistic regression analysis was used to evaluate the odds ratio of bone metastasis in PCa patients. The predictive value of age, race, marital status, and tumor characteristics were compared. The survival of patients with different socioeconomic statuses and bone metastasis statuses was compared by Kaplan–Meier analysis. A total of 1,335 patients with prostate cancer diagnosed between 2009 and 2015 were enrolled from the Second Affiliated Hospital of Zhejiang University School of Medicine. The survival of patients with different prostate-specific antigen (PSA) levels, Gleason scores, marital statuses and bone metastasis statuses was compared by Kaplan-Meier analysis. In SEER database, 96.74% of patients were 50 years of age or older. Multivariate Cox analysis revealed that for PCa patients, age at presentation, older age, single marital status, lower socioeconomic status, higher PSA level, T1 and N0 stage, and bone metastasis were independent risk factors for increased mortality. Multivariate logistic regression analysis revealed that patients who were married, were living in urban areas, had lower PSA levels, underwent surgery, and radiation had lower OR factors for bone metastasis. Asian or Pacific Islander, better socioeconomic status, lived in urban areas, married marital status, lower PSA levels and lower Gleason scores were better prognostic factors in PCa. Additionally, patients with single or divorced marital status, who were living in rural places had higher PSA levels, and T1 and N0 stages have a high OR for bone metastasis.

BackgroundWilms’ tumor 1-associating protein (WTAP) is a nuclear protein, which is ubiquitously expressed in many tissues. Furthermore, in various types of malignancies WTAP is overexpressed and plays a role as an oncogene. The function of WTAP in diffuse large B-cell lymphoma (DLBCL), however, remains unclear.MethodsImmunohistochemistry was applied to evaluate the levels of WTAP expression in DLBCL tissues and normal lymphoid tissues. Overexpression and knock-down of WTAP in DLBCL cell lines, verified on mRNA and protein level served to analyze cell proliferation and apoptosis in DLBCL cell lines by flow cytometry. Finally, co-immunoprecipitation (Co-IP), IP, and GST-pull down assessed the interaction of WTAP with Heat shock protein 90 (Hsp90) and B-cell lymphoma 6 (BCL6) as well as determined the extend of its ubiquitinylation.ResultsWTAP protein levels were consistently upregulated in DLBCL tissues. WTAP promoted DLBCL cell proliferation and improved the ability to confront apoptosis, while knockdown of WTAP in DLBCL cell lines allowed a significant higher apoptosis rate after treatment with Etoposide, an anti-tumor drug. The stable expression of WTAP was depended on Hsp90. In line, we demonstrated that WTAP could form a complex with BCL6 via Hsp90 in vivo and in vitro.ConclusionWTAP is highly expressed in DLBCL, promoting growth and anti-apoptosis in DLBCL cell lines. WTAP is a client protein of Hsp90 and can appear in a complex with BCL6 and Hsp90 in DLBCL. Down-regulation of WTAP could improve the chemotherapeutic treatments in DLBCL.Electronic supplementary materialThe online version of this article (10.1186/s12964-018-0258-6) contains supplementary material, which is available to authorized users.

No abstract

Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6. Therefore, we sought to explore the feedback loop between LITAF and BCL6 in B-NHL. Here, our data for the first time show that LITAF can repress expression of BCL6 by binding to Region A (−87 to +65) containing a putative LITAF-binding motif (CTCCC) within the BCL6 promoter. Furthermore, the regulation of BCL6 targets (PRDM1 or c-Myc) by LITAF may be associated with B-cell differentiation. Results also demonstrate that ectopic expression of LITAF induces cell apoptosis, activated by releasing cytochrome c, cleaving PARP and caspase 3 in B-NHL cells whereas knockdown of LITAF robustly protected cells from apoptosis. Interestingly, BCL6, in turn, could reverse cell apoptosis mediated by LITAF. Collectively, our findings provide a novel apoptotic regulatory pathway in which LITAF, as a transcription factor, inhibits the expression of BCL6, which leads to activation of the intrinsic mitochondrial pathway and tumor apoptosis. Our study is expected to provide a possible biomarker as well as a target for clinical therapies to promote tumor cell apoptosis.

Epithelial–mesenchymal transition (EMT) profoundly impacts prognosis and immunotherapy of clear cell renal cell carcinoma (ccRCC). However, not every patient is tested for EMT status because this requires additional genetic studies. In this study, we developed an EMT gene signature to classify the H&E-stained slides from The Cancer Genome Atlas (TCGA) into epithelial and mesenchymal subtypes, then we trained a deep convolutional neural network to classify ccRCC which according to our EMT subtypes accurately and automatically and to further predict genomic data and prognosis. The clinical significance and multiomics analysis of the EMT signature was investigated. Patient cohorts from TCGA (n = 252) and whole slide images were used for training, testing, and validation using an algorithm to predict the EMT subtype. Our approach can robustly distinguish features predictive of the EMT subtype in H&E slides. Visualization techniques also detected EMT-associated histopathological features. Moreover, EMT subtypes were characterized by distinctive genomes, metabolic states, and immune components. Deep learning convolutional neural networks could be an extremely useful tool for predicting the EMT molecular classification of ccRCC tissue. The underlying multiomics information can be crucial in applying the appropriate and tailored targeted therapy to the patient.

Early diagnosis of pancreatic cancer, one of the most deadly cancers with low survival rates, is difficult, and effective biomarkers are urgently needed. Lipopolysaccharide-induced tumor necrosis factor-α factor (LITAF) has been recently proposed as a potential tumor suppressor gene in several types of cancer. Here, we analyzed the biological function of LITAF in pancreatic cancer. The LITAF gene and protein levels were decreased in pancreatic tumor tissues compared with their paired adjacent non-cancerous tissues. In addition, patients with the lower LITAF protein expression had lower disease-free survival rates. The decreased LITAF expression correlated with LITAF promoter hypermethylation in pancreatic cancer cells and tissues. Moreover, promoter demethylation dose-dependently increased the LITAF transcription. Importantly, LITAF demethylation suppressed proliferation and cell cycle progression, and enhanced apoptosis of pancreatic cancer cells. Together, our results indicate that LITAF functions as a tumor suppressor gene in pancreatic cancer cells, and might serve as a novel biomarker for early diagnosis of pancreatic cancer.

This study investigated the expression of some frequently used immunohistochemistry (IHC) markers. Besides, we evaluated their correlations with the clinical features and outcomes of intrahepatic cholangiocarcinoma (ICC). Patients who underwent surgical removal of the ICC tumors were followed up for 4 years. The paraffin-embedded sections were used to obtain different markers, including CK7, CK19, CK20, CDX2, Glypican3, Hepa1, Ki-67, Villin, and SATB1. Overall survival in relation to IHC marker expression patterns and other clinical characteristics was evaluated by Kaplan-Meier survival curve and log-rank test, followed by the Cox proportional hazard model (to evaluate the relationship between multiple factors and the overall postoperative survival). A total of 122 ICC patients (67 males and 55 females, averagely aged 57.75) were included in this study. There were 44 cases with vascular invasion, 46 cases with lymphatic metastasis, and 13 cases with distant metastasis. CK7 was negatively correlated with lymphatic metastasis; and in distant-metastasis cases, the positive ratio of SATB1 was lower. Interestingly, SATB1 expression indicated a poorer survival, while Villin expression was associated with a better survival. The COX regression analysis showed that female was a protective factor versus male, Villin expression was a strong protective factor, and Ki-67 expression was correlated with a poor survival. Together, IHC markers are associated with tumor features and postoperative survival, especially for SATB1 as a risk factor and Villin as a protective marker, and female ICC patients may have better survival than males.

Background The incidence of multiple primary malignant tumors (MPMTs) is rising due to the development of screening technologies, significant treatment advances and increased aging of the population. For patients with a prior cancer history, identifying the tumor origin of the second malignant lesion has important prognostic and therapeutic implications and still represents a difficult problem in clinical practice. Methods In this study, we evaluated the performance of a 90-gene expression assay and explored its potential diagnostic utility for MPMTs across a broad spectrum of tumor types. Thirty-five MPMT patients from Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University and Fudan University Shanghai Cancer Center were enrolled; 73 MPMT specimens met all quality control criteria and were analyzed by the 90-gene expression assay. Results For each clinical specimen, the tumor type predicted by the 90-gene expression assay was compared with its pathological diagnosis, with an overall accuracy of 93.2% (68 of 73, 95% confidence interval 0.84–0.97). For histopathological subgroup analysis, the 90-gene expression assay achieved an overall accuracy of 95.0% (38 of 40; 95% CI 0.82–0.99) for well-moderately differentiated tumors and 92.0% (23 of 25; 95% CI 0.82–0.99) for poorly or undifferentiated tumors, with no statistically significant difference (p-value > 0.5). For squamous cell carcinoma specimens, the overall accuracy of gene expression assay also reached 87.5% (7 of 8; 95% CI 0.47–0.99) for identifying the tumor origins. Conclusions The 90-gene expression assay provides flexibility and accuracy in identifying the tumor origin of MPMTs. Future incorporation of the 90-gene expression assay in pathological diagnosis will assist oncologists in applying precise treatments, leading to improved care and outcomes for MPMT patients.