Analisys of Immunohistochemical Prognostic Markers in Canine Mammary Cancer and Its Relation to Postsurgical Survival

Background: Several animal models, including dogs, have been useful to compare the pathogenesis of mammary neoplasm in humans, showing biological parallelism in the growth and development of breast cancer. The causes of cancer could be attributed to change in several tumor suppressor genes. The relationship between molecule associated to senescence and clinical prognosis of patients affected by mammary cancer is little known. Beyond a collection of data, the major interest of the present study was to carry out a clinical follow-up of patients affected by these tumors, through association with new molecular markers by immunohistochemical technic. Upon completing the study, 15 patients survived, while 45 died. In the case of malignant neoplasms, 40 patients died because of the illness. The type of surgery most used by veterinarian surgeons was the simple lumpectomy, followed by the regional mastectomy. Sentinel node was removed by surgery only when clearly affected. Result: Markings against steroid hormones were positive. Regarding the markings against HER2 and Ki-67, they were negative in all cases. The markings against P53 and CD31 were all positives. Markings against molecules associated with cellular senescence were all positives. No statistical differences were found in immunomarcation for the different antigens used as clinical prognosis factors in mammary neoplasms. Conclusions: According to the study conditions, the survival of patients affected by breast tumors is directly related to diagnosis and malignancy histological grade, but not to animal breed, number of affected glands or patient reproductive status. On the other hand, immunohistochemical markings were not related to the patient prognosis. For this reason, it is important to highlight the persistance of a high percentage of mammary neoplasm cases clinically diagnosed with poor results on patient survival. Thus, educating owners and veterinarians for using diagnostic available tools to improve the prognosis after surgical animals affected by breast cancer is quite necessary.

Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer

BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer prognosis.This study invest-igated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer,and compared the predictive ability of the CONUT score with other indexes.AIM To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection.METHODS This retrospective analysis included 217 patients with newly diagnosed colorectal.The CONUT score was calculated based on the serum albumin level,total lymphocyte count,and total cholesterol level.The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve.The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis.RESULTS Using the cutoff value of the CONUT score,patients were stratified into CONUT low(n=189)and CONUT high groups(n=28).The CONUT high group had worse overall survival(OS)(P=0.013)and relapse-free survival(RFS)(P=0.015).The predictive performance of CONUT was superior to the modified Glasgow prognostic score,the prognostic nutritional index,and the neutrophil-to-lymphocyte ratio.Meanwhile,the predictive performances of CONUT+tumor node metastasis(TNM)stage for 3-year OS[area under the receiver operating characteristics curve(AUC)=0.803]and 3-year RFS(AUC=0.752)were no less than skeletal muscle mass index(SMI)+TNM stage.The CONUT score was negatively correlated with SMI(P<0.01).CONCLUSION As a nutritional indicator,the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer,and its predictive ability was superior to other indexes.The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

Prognostic markers for idiopathic pulmonary arterial hypertension

Objective The objective of this study is to review the research on the prognostic markers of idiopathic pulmonary arterial hypertension （IPAH）.Date sources We searched literature from PubMed and CNKI databases both in English and Chinese up to 2013.Study selection Data about mortality and cut-off value are from clinical trials and identified by analysis.Results IPAH is an unexplained,progressive,and rare disease characterized by increased pulmonary artery pressure and pulmonary vascular resistance.The diagnosis is difficult,mortality of IPAH is high,and the survival periods are only 2-3 years after diagnosis.Investigations in recent years have identified a range of prognostic markers for IPAH,including the 6-minute walking test,red blood cell distribution width,and platelet levels,as well as imaging findings.Changes in these markers are important sources of information to predict the prognosis of patients with IPAH,which carries significant benefits for treatment planning.Conclusion Even though the prognosis of IPAH has been investigated,the mortality is also high.More accurate and meaningful assessment for the prognosis of IPAH is required.

Lipid metabolism-related long noncoding RNA RP11-817I4.1 promotes fatty acid synthesis and tumor progression in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most common types of tumors.The influence of lipid metabolism disruption on the development of HCC has been demonstrated in published studies.AIM To establish an HCC prognostic model for lipid metabolism-related long non-coding RNAs(LMR-lncRNAs)and conduct in-depth research on the specific role of novel LMR-lncRNAs in HCC.METHODS Correlation and differential expression analyses of The Cancer Genome Atlas data were used to identify differentially expressed LMR-lncRNAs.Quantitative real-time polymerase chain reaction analysis was used to evaluate the expression of LMR-lncRNAs.Nile red staining was employed to observe intracellular lipid levels.The interaction between RP11-817I4.1,miR-3120-3p,and ATP citrate lyase(ACLY)was validated through the performance of dual-luciferase reporter gene and RIP assays.RESULTS Three LMR-lncRNAs(negative regulator of antiviral response,RNA transmembrane and coiled-coil domain family 1 antisense RNA 1,and RP11-817I4.1)were identified as predictive markers for HCC patients and were utilized in the construction of risk models.Additionally,proliferation,migration,and invasion were reduced by RP11-817I4.1 knockdown.An increase in lipid levels in HCC cells was significantly induced by RP11-817I4.1 through the miR-3120-3p/ACLY axis.CONCLUSION LMR-lncRNAs have the capacity to predict the clinical characteristics and prognoses of HCC patients,and the discovery of a novel LMR-lncRNAs,RP11-817I4.1,revealed its role in promoting lipid accumulation,thereby accelerating the onset and progression of HCC.

Interaction between inflammatory bowel disease,physical activity,and myokines:Assessment of serum irisin levels

Inflammatory bowel disease(IBD),including Crohn’s disease and ulcerative colitis,showed a wide spectrum of intestinal and extra-intestinal manifestations,which rendered the patients physically inactive and impaired their quality of life.It has been found that physical activity is a non-pharmacological intervention that improves the quality of life for those patients.Irisin is one member of the myokines secreted by muscle contraction during exercise and could be used as an antiinflammatory biomarker in assessing the physical activity of IBD patients.In addition,experimental studies showed that exogenous irisin significantly decreased the inflammatory markers and the histological changes of the intestinal mucosa observed in experimental colitis.Furthermore,irisin produces changes in the diversity of the microbiota.Therefore,endogenous or exogenous irisin,via its anti-inflammatory effects,will improve the health of IBD patients and will limit the barriers to physical activity in patients with IBD.

Clinical diagnosis and management of pancreatic cancer: Markers, molecular mechanisms, and treatment options

Pancreatic cancer(PC)is the third-leading cause of cancer deaths.The overall 5-year survival rate of PC is 9%,and this rate for metastatic PC is below 3%.However,the PC-induced death cases will increase about 2-fold by 2060.Many factors such as genetic and environmental factors and metabolic diseases can drive PC development and progression.The most common type of PC in the clinic is pancreatic ductal adenocarcinoma,comprising approximately 90%of PC cases.Multiple pathogenic processes including but not limited to inflammation,fibrosis,angiogenesis,epithelial-mesenchymal transition,and proliferation of cancer stem cells are involved in the initiation and progression of PC.Early diagnosis is essential for curable therapy,for which a combined panel of serum markers is very helpful.Although some mono or combined therapies have been approved by the United States Food and Drug Administration for PC treatment,current therapies have not shown promising outcomes.Fortunately,the development of novel immunotherapies,such as oncolytic viruses-mediated treatments and chimeric antigen receptor-T cells,combined with therapies such as neoadjuvant therapy plus surgery,and advanced delivery systems of immunotherapy will improve therapeutic outcomes and combat drug resistance in PC patients.Herein,the pathogenesis,molecular signaling pathways,diagnostic markers,prognosis,and potential treatments in completed,ongoing,and recruiting clinical trials for PC were reviewed.

Onodera's Prognostic Nutritional Index is a novel and useful prognostic marker for gastrointestinal stromal tumors

BACKGROUND Immunoinflammatory markers such as the peripheral blood neutrophil-tolymphocyte ratio(NLR)and the platelet-to-lymphocyte ratio(PLR)have gained considerable attention as prognostic markers in gastrointestinal stromal tumors(GISTs).AIM To assess the prognostic value of Onodera’s Prognostic Nutritional Index(OPNI)for GISTs.METHODS All patients who had undergone surgical resection for a primary,localized GIST from 2009 to 2016 at our cancer center were initially and retrospectively identified.Recurrence-free survival(RFS)was calculated by the Kaplan-Meier method and compared by the log-rank test.We used multivariate Cox proportional hazard regression models to identify associations with outcome variables.RESULTS A total of 235 GISTs were identified and included for analysis under our inclusion criteria.Univariate and multivariate analyses both identified the OPNI as an independent prognostic marker,and the OPNI was associated with the primary site,tumor size,mitotic index,tumor rupture,necrosis,and modified NIH risk classification.Low OPNI(<51.30;hazard ratio=5.852;95% confidence interval:1.072–31.964;P=0.0414)was associated with worse RFS.The 2-and 5-year RFS rates of the patients with a low OPNI were 92.83% and 76.22%,respectively,whereas 100% and 98.41% were achieved by the patients with a high OPNI.CONCLUSION The preoperative OPNI is a novel and useful prognostic marker for GISTs.

Integrating transcriptomes and somatic mutations to identify RNA methylation regulators as a prognostic marker in hepatocellular carcinoma

Background:RNA methylation modifying plays an important role in the occurrence and progression of a range of human cancers including hepatocellular carcinoma(HCC),which is characterized by a mass of genetic and epigenetic alterations.However,the treatment targeting these alterations is limited.Methods:We used comprehensive bioinformatics analysis to analyze the correlation between cancerassociated RNA methylation regulators and HCC malignant features in network datasets.Results:We identified two HCC subgroups(cluster 1 and 2),which had clearly distinct clinicopathological,biofunctional and prognostic characteristics,by consensus clustering.The cluster 2 subgroup correlated with malignancy of the primary tumor,higher tumor stage,higher histopathological grade and higher frequency of TP53 mutation,as well as with shorter survival when compared with cluster 1.Gene enrichment indicated that the cluster 2 correlated to the tumor malignancy signaling and biological processes.Based on these findings,an 11-gene risk signature was built,which not only was an independent prognostic marker but also had an excellent power to predict the tumor features.Conclusions:Our study indicated that RNA methylation regulators are vital for HCC malignant progression and provide an important evidence for RNA methylation,methylation regulators are actionable targets for anticancer drug discovery.

Identification of prognostic indicators,diagnostic markers, and possible therapeutic targets among LIM homeobox transcription factors in breast cancer

Background:Breast cancer(BRCA)is the most common malignant tumor among women worldwide.Despite advances in treatment,many patients still die from a lack of effective diagnostic and prognostic markers and powerful therapeutic targets.LIM homeobox genes(LHXs)play vital roles in regulating the development of various organisms.However,there are limited reports regarding their roles in the diagnosis,prognosis,and treatment of BRCA.Methods:UALCAN,Kaplan–Meier plotter,cBioPortal,GeneMANIA,STRING,DAVID 6.8,TRRUST v2,LinkedOmics,and TIMER were utilized to analyze differential expression,prognostic value,genetic alteration,neighbor gene network,transcription factor targets,kinase targets,and immune cell infiltration of LHXs in BRCA patients.Results:LHX gene expression patterns are clear in BRCA and its different subtypes.Further analyses indicated that this altered expression is possibly affected by genetic and/or epigenetic changes.The prognostic and diagnostic values of certain LHXs are unique to different BRCA subtypes.LHXs are mainly involved in the regulation of differentiation and development,and their neighbor genes are primarily involved in cancer‐related pathways.Moreover,most LHXs are closely correlated with immune cell infiltration.Furthermore,LHXs may exert their functions by regulating a series of transcription factor and kinase targets.Conclusions:LHXs are unique diagnostic and prognostic markers and participate in cancer through different signaling pathways and/or regulatory mechanisms in BRCA.This study provides potential applications of LHXs for the diagnosis,prognosis,and treatment of BRCA and its different subtypes.

The relationship between SPARC expression in primary tumor and metastatic lymph node of resected pancreatic cancer patients and patients' survival

BACKGROUND： Previous researches in pancreatic cancer demonstrated a negative correlation between secreted protein acidic and rich in cysteine （SPARC） expression in primary tumor and survival, but not for SPARC expression in lymph node. In the present study, we aimed to evaluate the SPARC expression in various types of tissues and its impact on patients＇ prognosis. METHODS： The expression of SPARC was examined by immunohistochemistry in resected pancreatic cancer specimens. Kaplan-Meier analyses and Cox proportional hazards regres- sion were applied to assess the mortality risk. RESULTS： A total of 222 tissue samples from 73 patients were collected to evaluate the SPARC expression, which included 73 paired primary tumor and adjacent normal tissues, 38 paired metastatic and normal lymph nodes. The proportion of posi tive SPARC expression in metastatic lymph node was high （32/38）, whereas in normal lymph node it was negative （0/38）. Positive SPARC expression in primary tumor cells was associ- ated with a significantly decreased overall survival （P=0.007） and disease-free survival （P=0.003）, whereas in other types of tissues it did not show a predictive role for prognosis. Univariate and multivariate analyses both confirmed this significance. CONCLUSION： SPARC can serve a dual function role as both predictor for prognosis and potentially biomarker for lymph node metastasis in resected pancreatic cancer patients.

Review of 10 years of research on breast cancer patients:Focus on indoleamine 2,3-dioxygenase

Therapeutic manipulation of the immune system in cancer has been an extensive area of research in the field of oncoimmunology.Immunosuppression regulates antitumour immune responses.An immunosuppressive enzyme,indoleamine 2,3-dioxygenase(IDO)mediates tumour immune escape in various malignancies including breast cancer.IDO upregulation in breast cancer cells may lead to the recruitment of regulatory T(T-regs)cells into the tumour microenvironment,thus inhibiting local immune responses and promoting metastasis.Immunosuppression induced by myeloid derived suppressor cells activated in an IDOdependent manner may enhance the possibility of immune evasion in breast cancer.IDO overexpression has independent prognostic significance in a subtype of breast cancer of emerging interest,basal-like breast carcinoma.IDO inhibitors as adjuvant therapeutic agents may have clinical implications in breast cancer.This review proposes future prospects of IDO not only as a therapeutic target but also as a valuable prognostic marker for breast cancer.

Role of the circulatory interleukin-6 in the pathogenesis of gliomas:A systematic review

BACKGROUND Glioma is the most common primary tumor in the brain originating from glial cells.In spite of extensive research,the overall survival rate is not enhanced.A number of published articles observed differentially circulating levels of cytokines in glioma.Interleukin-6(IL-6)protein coded by IL-6 gene is regulated by the immune system and it has been found to have a significant role in progression and apoptosis resistance of glioma.AIM To review the role of circulatory IL-6 in the development and progression of glioma and its utility as a biomarker.METHODS Preferred Reporting Items for Systematic Reviews and Meta-analysis(PRISMA)guidelines were applied to filter the relevant studies based on inclusion and exclusion criteria.We used a combination of keywords and the Reference Citation Analysis(RCA)tool to search the potential studies and performed data extraction from selected studies.RESULTS The published results were inconsistent;however,most studies showed a significantly higher IL-6 level in glioma cases as compared to controls.Comparative IL-6 level among the different grades of glioma showed a higher level with low-grade gliomas and lower level with high-grade gliomas.CONCLUSION IL-6 level significantly differed between cases and controls,and among different cancer stages,which shows its potential as a diagnostic and prognostic marker.

Mismatch repair, minichromosome maintenance complex component 2, cyclin A, and transforming growth factor β receptor type Ⅱ as prognostic factors for colorectal cancer： results of a 10-year prospective study using tissue microarray analysis

Background The expression of genes encoding a number of pathogenetic pathways involved in colorectal cancer could potentially act as prognostic markers. Large prospective studies are required to establish their relevance to disease prognosis.Methods We investigated the relevance of 19 markers in 790 patients enrolled in a large randomised trial of 5-fluorouracil using immunohistochemistry and chromogenic in situ hybridisation. The relationship between overall 10-year survival and marker status was assessed.Results Minichromosome maintenance complex component 2 （MCM2） and cyclin A were significantly associated with overall survival. Elevated MCM2 expression was associated with a better prognosis （HR=0.63, 95%CI： 0.46-0.86）.Cyclin A expression above the median predicted an improved patient prognosis （HR=0.71, 95%CI： 0.53-0.95）. For mismatch repair deficiency and transforming growth factor β receptor type Ⅱ （TGFBRII） overexpression there was a borderline association with a poorer prognosis （HR=0.69, 95%C/： 0.46-1.04 and HR=2.11, 95%CI： 1.02-4.40,respectively）. No apparent associations were found for other markers.Conclusion This study identified cell proliferation and cyclin A expression as prognostic indicators of patient outcome in colorectal cancer.

Pan-cancer analysis identifies RNA helicase DDX1 as a prognostic marker

The DEAD-box RNA helicase(DDX)family plays a critical role in the growth and development of multiple organisms.DDX1 is involved in mRNA/rRNA processing and mature,virus replication and transcription,hormone metabolism,tumo-rigenesis,and tumor development.However,how DDX1 functions in various cancers remains unclear.Here,we explored the potential oncogenic roles of DDX1 across 33 tumors with The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases.DDX1 is highly expressed in breast cancer(BRCA),cholangiocarcinoma(CHOL),and colon adenocarcinoma(COAD),but it is lowly expressed in renal cancers,including kidney renal clear cell carcinoma(KIRC),kidney chromophobe(KICH),and kidney renal papillary cell carcinoma(KIRP).Low expression of DDX1 in KIRC is cor-related with a good prognosis of overall survival(OS)and disease-free survival(DFS).Highly expressed DDX1 is linked to a poor prognosis of OS for adrenocortical carcinoma(ACC),bladder urothelial carcinoma(BLCA),KICH,and liver hepatocellular carcinoma(LIHC).Also,the residue Ser481 of DDX1 had an enhanced phosphorylation level in BRCA and ovarian cancer(OV)but decreased in KIRC.Immune infiltration analysis exhibited that DDX1 expression affected CD8+T cells,and it was significantly associated with MSI(microsatellite instability),TMB(tumor mutational burden),and ICT(immune checkpoint blockade therapy)in tumors.In addition,the depletion of DDX1 dramatically affected the cell viability of human tumor-derived cell lines.DDX1 could affect the DNA repair pathway and the RNA transport/DNA replication processes during tumorigenesis by analyzing the CancerSEA database.Thus,our pan-cancer analysis revealed that DDX1 had complicated impacts on different cancers and might act as a prognostic marker for cancers such as renal cancer.

Nucleolar protein 6 promotes cell proliferation and acts as a potential novel prognostic marker for hepatocellular carcinoma

Background:Nucleolar protein 6(NOL6)is a nucleolar RNA-associated protein that is highly conserved between species.It has been proved to be associated with the prognosis of liver cancer.However,the underlying mechanism has not been fully established.This study aimed to assess the relationship between NOL6 and liver cancer prognosis.Methods:We constructed anNOL6-short hairpin RNA(shRNA)-expressing lentivirus.Through viral transfection,cell growth assay and fluorescence-activated cell sorting,we evaluated the effect of shRNA-mediatedNOL6 knockdown on the proliferation,colony formation,and apoptosis of hepatocellular carcinoma(HCC)cells.The relationship betweenNOL6 expression and HCC patient survival has been established through bioinformatics analysis.We also explored the downstream molecular regulatory network ofNOL6 in HCC by performing an Ingenuity Pathway Analysis in the database.Results:IncreasedNOL6 expression was detected in HCC cells compared to normal controls;HCC patients with highNOL6 expression had poorer prognoses than those with low expression.NOL6 knockdown inhibited HCC cell proliferation,apoptosis,and colony formation.Also,MAPK8,CEBPA,andFOSL1 were selected as potential downstream genes ofNOL6.Conclusions:NOL6 up-regulates HCC cell proliferation and affects downstream expression of related genes.Moreover,NOL6 is considered to be associated with poor prognosis in HCC patients.

LPCAT1 functions as a novel prognostic molecular marker in hepatocellular carcinoma

This study aimed to investigate the relationships between LPCAT1 expression and clinicopathologic parameters of hepatocellular carcinoma(HCC),further,to explore the effect of LPCAT1 on overall survival(OS)in patients with HCC,and its possible mechanism.Bioinformatics analysis using high throughput RNA-sequencing data from TCGA was utilized to explore the differential expression of LPCAT1 between normal and tumor tissues,and the associations between LPCAT1 expression and clinicopathological parameters.Survival analyses and subgroup survival analyses were utilized to elucidate the effect of LPCAT1 on OS in patients with HCC.Univariate analysis and multivariate analysis were used to investigate the prognostic factors.Potential LPCAT1 related tumor genes were identified by the methodology of differentially expressed genes(DEGs)screening.GO term enrichment analysis,KEGG pathway analysis and the PPI network were used to explore the potential mechanism.LPCAT1 was significantly overexpressed in HCC tumor tissues compared with normal tissues.The LPCAT1 expression was related to tumor grade,ECOG score,AFP and TNM stage,with P values of 0.000,0.000,0.007 and 0.000,respectively.Multivariate analysis demonstrated that LPCAT1 expression was independently associated with OS,with an HR of 1.04(CI:1.01–1.06,P=0.003).The KEGG pathway enrichment analyses showed that overlapped DEGs mainly participate in the cell cycle.Finally,we identified a hub gene,CDK1,which has been reported to act on the cell cycle,consistent with the result of KEGG enrichment analysis.Collectively,these data confirmed LPCAT1 was upregulated in HCC,and was an independent predictor of the prognosis.

USP33, a new player in lung cancer, mediates Slit-Robo signaling

Ubiquitin specific protease 33 （USP33） is a multifunctional protein regulating diverse cellular processes. The expression and role of USP33 in lung cancer remain unexplored. In this study, we show that USP33 is down-regulated in multi- ple cohorts of lung cancer patients and that low expression of USP33 is associated with poor prognosis. USP33 medi- ates Slit-Robo signaling in lung cancer cell migration. Downregulation of USP33 reduces the protein stability of Robol in lung cancer cells, providing a previously unknown mechanism for USP33 function in mediating Slit activity in lung cancer ceils. Taken together, USP33 is a new player in lung cancer that regulates Slit-Robo signaling. Our data suggest that USP33 may be a candidate tumor suppressor for lung cancer with potential as a prognostic marker.

Role of Regulatory T cell in Clinical Outcome of Traumatic Brain Injury

Background： Traumatic brain injury （TBI） is a life-threatening disease worldwide. Regulatory T cells （Treg ceils） were involved in the immunological system in central nervous system. It is defined as a subpopulation of CD4＋ cells that express CD25 and transcription lactor forkhead box P3. The level of circulating Treg cells increases in a variety of pathologic conditions. The purpose of this study was to uncover the role of circulating Treg cells in TBI. Methods： A clinical study was conducted in two neurosurgical intensive care units of Tianjin Medical University General Hospital and Second Hospital of Tianjin Medical University （Tianjin, China）. Forty patients and 30 healthy controls were recruited t＇rom August 2013 to November 2013. Circulating Treg cells was detected on the follow-up period of 1,4, 7, 14, and 21 days alter TBI. Blood sample （ 1 ml） was withdrawn in the morning and processed within 2 h. Results： There was no significant difference in the level of circulating Treg cells between TBI patients and normal controls during follow-up. TBI patients exhibited higher circulating Treg level than normal controls on the 1st day after TBI. Treg level was decreased on the 4th day, climbed tip on the 7th day and peaked on 14th day after TBI. Treg cells declined to the normal level on 21th day alter TBI. The level of circulating Treg cells was significantly higher in survival TBI patients when compared to nonsurvival TBI patients. TBI patients with improved conditions exhibited significantly higher circulating Treg level when compared to those with deteriorated conditions. The circulating Treg level was correlated with neurologic recovery after TBI. A better neural recovery and lower hospital mortality were found in TBI patients with circulating Treg cells more than 4.91% in total CD4＋ inononuclear cells as compared to those with circulating Treg cells less than 4.91% in total CD4 mononuclear cells in the first 14 days. Conclusions： The level of circulating Treg cells is positively correlated with clinical outcome of TBI. The level of Treg cells predicts the progress for TBI patients and may be a target in TBI treatment.

Identification of TWIST-interacting genes in prostate cancer

Prostate cancer is one of the most common cancers in men worldwide, and the number of diagnosed patients has dramatically increased in recent years. Currently, the clinical parameters used to diagnose prostate cancer, such as Gleason score, pathological tumor staging, and prostate-specific antigen(PSA) expression level, are considered insufficient to inform recommendation to guide clinical practice. Thus, identification of a novel biomarker is necessary. TWIST is one of the well-studied targets and is correlated with cancer invasion and metastasis in several human cancers. We have investigated two largest prostate cancer patient cohorts available in GEO database and found that TWIST expression is positive correlated with Gleason score and associated with poorer survival. By using a prostate cancer cohort and a prostate cancer cell line dataset, we have identified three potential downstream targets of TWIST, PPM1 A, SRP72 and TBCB. TWIST's prognostic capacity is lost when the gene is mutated. Further investigation in the prostate cancer cohort revealed that gene expression of SERPINA, STX7, PDIA2, FMP5, GP1 BB, VGLL4,KCNMA1, SHMT2, SAA4 and DIDO1 influence the prognostic significance of TWIST and vice versa. Importantly, eight out of these ten genes are prognostic indicator by itself. In conclusion, our study has further confirmed that TWIST is a prognostic marker in prostate cancer, identified its potential downstream targets and genes that could possibly give additional prognostic value to predict TWIST-mediated prostate cancer progression.

Evaluation of microRNA-146a expression in acute lymphoblastic leukemia

MicroRNAs （miRNAs） play an essential role in the development and progression of acute lymphoblastic leukemia （ALL）, and could serve as disease biomarkers and therapeutic targets. The function of miR-146a in lymphoid differentiation has been here with discussed. However, the role of this miRNA in the outcome of ALL is not well understood. Peripheral blood of 48 patients with ALL and 20 age- and sex-matched healthy control subjects was used to accurately evaluate the expression of miR-146a by stem-loop Real time PCR. No statistically significant difference was found between patients and controls in total miR-146a expression. The expression of miR-146a was high （18.75%）, low （27.08~o） and not different （54.17%） in ALL patients. Our analysis indicated no association between the expression of miR-146a and any prognostic factors such as WBC/PLT counts, Hb, fusion genes （P190 and some translocations） with ALL type. This study revealed that miR-146a cannot be an independent factor for predicting the outcome of ALL patients. We suggest a multi-parameter analysis including miRNAs, transcription factors and critical genes to achieve a precise clinical panel for prognostic values.