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The tumor immunosuppressive microenvironment can influence treatment response and outcomes. A previously validated immunosuppression scoring system (ISS) assesses multiple immune checkpoints in gastric cancer (GC) using tissue-based assays. We aimed to develop a radiological signature for non-invasive assessment of ISS and treatment outcomes.A total of 642 patients with resectable GC from three centers were divided into four cohorts. Radiomic features were extracted from portal venous-phase CT images of GC. A radiomic signature for predicting ISS (RISS) was constructed using the least absolute shrinkage and selection operator (LASSO) regression method. Moreover, we investigated the value of the RISS in predicting survival and chemotherapy response.The RISS, which consisted of 10 selected features, showed good discrimination of immunosuppressive status in three independent cohorts (area under the curve = 0.840, 0.809, and 0.843, respectively). Multivariate analysis revealed that the RISS was an independent prognostic factor for both disease-free survival (DFS) and overall survival (OS) in all cohorts (all p 0.05). Further analysis revealed that stage II and III GC patients with low RISS exhibited a favorable response to adjuvant chemotherapy (OS: hazard ratio [HR] 0.407, 95% confidence interval [CI] 0.284-0.584); DFS: HR 0.395, 95% CI 0.275-0.568). Furthermore, the RISS could predict prognosis and select stage II and III GC patients who could benefit from adjuvant chemotherapy independent of microsatellite instability status and Epstein-Barr virus status.The new, non-invasive radiomic signature could effectively predict the immunosuppressive status and prognosis of GC. Moreover, the RISS could help identify stage II and III GC patients most likely to benefit from adjuvant chemotherapy and avoid overtreatment.

To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) from low-endemic regions of China who received definitive intensity-modulated radiation therapy (IMRT). The clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January, 2008 to December, 2013 were retrospectively reviewed. All patients received definitive IMRT, and 87.7% received platinum-based chemotherapy. The median follow-up duration was 51 months (follow-up rate, 98.5%; range, 10–106 months) for the entire cohort. The 5-year overall survival rate was 79.7%. The 5-year local relapse-free survival rate, regional relapse-free survival rate, distant metastasis-free survival rate and progression-free survival rate were 92.4%, 93.3%, 79.2% and 74.3%, respectively. A total of 153 patients had experienced treatment failure, with distant metastasis as the primary cause in 77.1% (118/153). Patients with T4 or N3 diseases had a significantly poorer prognosis than other subcategories. Stage T4 and N3 were closely associated with distant metastasis, with the metastatic rate of 29.3% and 45.5%, respectively. IMRT provides patients with non-metastatic NPC with satisfactory long-term survival. Both T stage and N stage are important prognostic factors for NPC patients. Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival time.

Lung cancer is the most common cause of cancer-related death in the world. Long non-coding RNAs (lncRNAs) are longer than 200 nucleotide transcripts, and are not translated into protein. The lncRNA linc00662 is overexpressed in lung cancer; however, its role in lung cancer is still unknown. In our study, by analyzing the TCGA data, we found that linc00662 was overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We knocked-down the expression of linc00662 using siRNA, and found that silencing linc00662 significantly inhibited the proliferation and colony formation of the lung cancer cell lines A549 and H460. We also found that knockdown of linc00662 increased the expression of the microRNA miR-145-5p and decreased the expression of the platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) gene. We further show that linc00662 binds with miR-145-5p, and that miR-145-5p binds to the 3′UTR of PAFAH1B2. miR-145-5p negatively regulates PAFAH1B2 both at the mRNA and the protein level. Loss of miR-145-5p abolished the inhibitory effects of silencing linc00662 on the proliferation and colony formation of A549 and H460 cells. These findings indicate that linc00662 functions as an oncogene by acting as a competing endogenous RNA (ceRNA) and sponges and regulates miR-145-5p in lung cancer, and thus may provide a potential target for treating lung cancer.

LncRNAs play a vital role in the tumorigenesis of gastric cancer (GC). This study determined that LINC01235 expression has greater fold changes by analyzing TCGA RNA-Seq data. The qRT-PCR assay confirmed that LINC01235 is significantly over-expressed in GC cells and tissues. Additionally, the overall survival analysis showed that patients with a higher LINC01235 expression had a poorer prognosis than those with a lower LINC01235 expression. Univariate Cox regression analysis indicated that high LINC01235 expression is positively correlated with poor prognosis. Moreover, LINC01235 was an independent poor prognostic marker for GC in multivariate Cox analysis. In vitro assays suggested that LINC01235 knockdown suppresses GC cell migration and invasion. GSEA revealed that high LINC01235 expression is strongly enriched in the EMT pathway. Western blotting results revealed that LINC01235 silencing decreases the expression of EMT-induced proteins. In conclusion, LINC01235 can promote GC cell metastasis via EMT and function as a prognostic biomarker.

Background It has been previously demonstrated that hyaluronan (HA) potentially regulates the initiation and propagation of bladder cancer (BLCA). HYAL3 encodes hyaluronidase and is a potential therapeutic target for BLCA. We aimed to explore the role that HYAL3 plays in BLCA pathogenesis. Methods HYAL3 expression in BLCA specimens was analyzed using The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) cohort as well as confirmed in cell lines and The Human Protein Atlas. Then, associations between HYAL3 expression and clinicopathological data were analyzed using survival curves and receiver-operating characteristic (ROC) curves. The functions of HYAL3 were further dissected using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and the protein–protein interaction network. Finally, we harnessed the Tumor IMmune Estimation Resource and Gene Expression Profiling Interactive Analysis to obtain correlations between HYAL3 expression, infiltrating immunocytes, and the corresponding immune marker sets. Results HYAL3 expression varied greatly between many types of cancers. In addition, a higher HYAL3 expression level predicted a poor overall survival (OS) in both TCGA-BLCA and GEO gene chips (P HYAL3 acted as an independent prognostic factor in BLCA patients and correlated with the infiltration of various types of immunocytes, including B cells, CD8+ T cells, cytotoxic cells, T follicular helper cells, and T helper (Th) 2 cells. Conclusion HYAL3 might serve as a potential biomarker for predicting poor OS in BLCA patients and correlated with immunocyte infiltration in BLCA.

Background: Carcinoembryonic antigen (CEA) is one of the important indexes for the diagnosis and prognosis of gastrointestinal cancer. Systemic inflammatory response (SIR) is closely related to the occurrence and development of gastrointestinal cancer. Methods: A total of 803 patients who underwent radical gastrectomy in Qinghai University Affiliated Hospital from January 2012 to December 2016 were included as training set. Multivariable Cox proportional hazard regression was used to identify associations with outcome of gastric cancer (GC). CNLR was established by combining CEA and the neutrophils to lymphocytes ratio (NLR, a typical parameter in SIR) to generate a novel prognostic score system and its prognostic value was externally validated. Results: Multivariate analysis showed that CEA and NLR were independent prognostic factors for GC patients (both p < 0.05). A higher CNLR was significantly associated with older age, male sex, larger tumor size, vascular invasion and advanced stages (all p < 0.05). Patients with higher CNLR had poor prognosis than those with lower CNLR (p < 0.05). Multivariate analysis showed that CNLR was an independent prognostic factor (p < 0.05). Incorporation of the CNLR into a prognostic model including age and TNM stage generated a nomogram, which predicted accurately 3- and 5-year survival for GC patients. And similar results were obtained in the external validation set. Conclusions: The CNLR prognostic scoring system established by combining CEA and NLR is an independent prognostic factor for GC, which can be incorporated into the traditional TNM staging to improve the prediction of long-term survival outcomes.

International audience; Background: Early biomarkers allowing effective treatment stratification in adult T-cell acute lymphoblastic leukemia (T-ALL) patients remain elusive.Materials and methods: The mutation spectrum of 116T-ALL adult patients enrolled in the Shanghai Institute of Hematology (SIH)-based hospital network or Multicenter Hematology-Oncology Protocols Evaluation System (M-HOPES) in China were studied by using RNA-sequencing or targeted next generation sequencing. A comprehensive survival analysis based on clinical characteristics, immunophenotype and oncogenetic classifier was performed.Results: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has higher mutation rates of N/K-RAS and lower mutation rates of FBXW7 compared to non-ETP ALL, but the survival probability of ETP-ALL patients is similar to that of non-ETP ALL patients. T-ALLs with a NOTCH1/FBXW7 (N/F) mutation in the absence of RAS or PTEN abnormalities (NFRP class I) show a more favorable outcome compared to T-ALLs with no N/F mutation and/or with the presence of RAS/PTEN alterations (NFRP class II). A survival analysis of TALL , taking into account both the ETP-ALL/non-ETP TALL groups and the NFRP oncogenetic classifier, demonstrates that, within the non-ETP TALL subtype, NFRP class II identifies a group with poor prognosis and significant decreases of both OS (14.8% versus 50.9%, P = 0.019) and EFS (11.4% versus 42.4%, P = 0.001). In contrast, no survival difference is observed within ETP-ALL between the NFRP class I or class II (OS: 37.9% versus 33%, P = 0.876; EFS: 39.8% versus 33.7%, P = 0.969).Conclusion: In summary, the oncogenetic classifier based on the NFRP classes is particularly useful to improve the stratification of non-ETP ALL.

Background In clinical practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are the most common markers measured before and after surgery for gastric cancer (GC). However, which pre- or post-operative combined tumour markers (CEA and CA19-9) have more prognostic value remains unclear. Methods Consecutive patients undergoing a resection for GC at the Fujian Medical University Union Hospital were included as a discovery database between January 2011 and December 2014. The prognostic impact of pre- and post-operative tumour markers was evaluated using Kaplan–Meier log-rank survival analysis and multivariable Cox regression analysis. The results were then externally validated. Results A total of 735 and 400 patients were identified in the discovery cohort and in the validation cohort, respectively. Overall survival rates decreased in a stepwise manner in association with the number of pre- and post-operative positive tumour markers (both P P Conclusion Pre-operative tumour markers have a better discriminatory ability for post-operative survival in GC patients than post-operative tumour markers, and the normalisation of tumour markers after surgery was associated with better survival.

Background Lung adenocarcinoma (LAD) is a highly aggressive malignant tumor which threatens the health and life of the population. Long non‐coding RNA X‐inactive specific transcript (XIST) and mouse double minute clone 2 (MDM2) are connected with the tumorigenesis of LAD. Nevertheless, whether MDM2 is regulated by XIST has not previously been reported in LAD. Methods Quantitative real‐time polymerase chain reaction (qRT‐PCR) was employed to detect the expression of XIST, microRNA‐363‐3p (miR‐363‐3p) and MDM2 in LAD tissues and cells. The proliferation, migration, invasion and apoptosis of LAD cells were determined by 3‐(4, 5‐dimethylthiazol‐2‐YI)‐2, 5‐diphenyltetrazolium bromide (MTT), transwell or flow cytometry assay, respectively. MDM2 protein level was detected using western blot analysis. Dual‐luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pulldown assay were performed to determine the interaction among XIST, miR‐363‐3p and MDM2. A xenograft tumor model was constructed to validate the effect of XIST on LAD cells in vivo. Results We found that XIST and MDM2 were remarkably elevated while miR‐363‐3p was reduced in LAD tissues and cells. Both XIST and MDM2 downregulation restrained proliferation, migration and invasion, and facilitated apoptosis of LAD cells in vitro. Importantly, XIST bound to miR‐363‐3p to modulate MDM2 expression in LAD cells. Moreover, miR‐363‐3p knockdown or MDM2 elevation reversed the effects of XIST downregulation on the proliferation, migration, invasion and apoptosis of LAD cells. Furthermore, XIST knockdown constrained tumor growth on LAD cells in vivo. Conclusions XIST knockdown repressed proliferation, migration and invasion, and accelerated apoptosis of LAD cells by downregulating MDM2 expression via binding to miR‐363‐3p. Key points Significant findings of the study XIST and MDM2 were abnormally enhanced in LAD tissues and cells. Both downregulation of XIST and MDM2 repressed proliferation, migration and invasion, and boosted apoptosis of LAD cells in vitro. XIST bound to miR‐363‐3p to regulate MDM2 expression in LAD cells. Downregulation of XIST impeded tumor growth on LAD cells in vivo. What this study adds This study confirmed that XIST was a potential target for inhibiting the development of LAD, and affords a possible strategy for the treatment of LAD in the future.

Objective: To evaluate the prognostic significance of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging classification for gastric cancer. Methods: Prospective databases were reviewed to identify patients who underwent radical gastrectomy at two specialized eastern centers. The prognostic value of the eighth edition TNM classification was estimated and compared with that of the seventh edition. Additional external validation was performed using a dataset from a Western population. Results: Significant differences in 5-year overall survival (OS) rates were observed for each TNM stage when using the eighth edition system, and smaller Akaike information criteria (AIC) values and a higher c-statistic were observed relative to those of the seventh edition. However, the OS rates in each subgroup of stage III patients based on the eighth edition were significantly different. Patients with the same pN stage, namely, the pT4a and pT4b groups, showed similar 5-year OS (P>0.05). Based on the survival data, we propose a simplified staging system. In the improved TNM (iTNM) staging system, the subgroups of a given TNM stage do not show statistically significant differences in OS. The iTNM staging exhibits superior prognostic stratification, with lower AIC values and a higher c-statistic than the eighth edition TNM classification. Similar results were obtained with the external validation dataset from the IMIGASTRIC database. Conclusion: The prognostic prediction of the eighth edition of the AJCC TNM classification is superior to that of the seventh edition. However, it remains associated with some stage migration. The iTNM staging system permits simplification and slightly better prognostic prediction.

Background T cell acute lymphoblastic leukemia (T-ALL) defines a group of hematological malignancies with heterogeneous aggressiveness and highly variable outcome, making therapeutic decisions a challenging task. We tried to discover new predictive model for T-ALL before treatment by using a specific pipeline designed to discover aberrantly active gene. Results The expression of 18 genes was significantly associated with shorter survival, including ACTRT2, GOT1L1, SPATA45, TOPAZ1 and ZPBP (5-GEC), which were used as a basis to design a prognostic classifier for T-ALL patients. The molecular characterization of the 5-GEC positive T-ALL unveiled specific characteristics inherent to the most aggressive T leukemic cells, including a drastic shut-down of genes located on the mitochondrial genome and an upregulation of histone genes, the latter characterizing high risk forms in adult patients. These cases fail to respond to the induction treatment, since 5-GEC either predicted positive minimal residual disease (MRD) or a short-term relapse in MRD negative patients. Conclusion Overall, our investigations led to the discovery of a homogenous group of leukemic cells with profound alterations of their biology. It also resulted in an accurate predictive tool that could significantly improve the management of T-ALL patients.

Objective: This work explores collateral circulation metrics, such as the anterior borderzone angle grading (ABZA-grading), as a predictor of the prognosis in patients with acute middle cerebral artery occlusion (MCAO) following endovascular treatment (EVT).Methods: Clinical data from 108 patients with acute MCAO, treated by EVT, were retrospectively analyzed. In patients with MCAO, ABZA is the angle between the median line of the sagittal sinus and the borderzone of the pial arterioles of ACA and MCA, and the ABZA/23.0° was rounded to obtain the corresponding collateral circulation score (ABZA-grading). In parallel, the primary outcome was defined as the 90-day clinical outcome by modified ranking scale score (mRS). Univariate analysis and logistic regression were used to analyze the independent predictors of the 90-day clinical outcome (mRS). Receiver operating characteristic curve (ROC) analysis was used to judge the predictive value of ABZA.Results: Univariate analysis and logistic regression analysis showed that ABZA-grading > 2 and age were independent predictors of the 90-day clinical outcome after EVT in patients with acute MCAO. The ROC analysis showed that ABZA alone could predict a favorable 90-day clinical outcome with an area under the curve (AUC) of 0.868. Using an ABZA of >57.8° (the corresponding ABZA-grading of >2) as the cut-off value, the predictive sensitivity and specificity were 75.7 and 88.7%, respectively. Contingency table analysis showed a statistical difference in mRS score between ABZA-grading subgroups, and ABZA-grading between stroke caused by large artery atherosclerosis (LAA) and cardiogenic embolism (CE).Conclusion: The ABZA-grading is an easy and objective assessment of collateral circulation that is independently associated with short-time clinical outcome after EVT in patients with acute MCAO. Therefore, it may guide selection of patients with acute ischemic stroke (AIS) suitable for EVT. The ABZA-grading of collateral circulation can be a supplemental metric to help differentiate stroke by LAA and CE.

Key Points Question Are there any differences in prognoses or recurrence patterns associated with gastric neuroendocrine carcinoma, mixed adenoneuroendocrine carcinoma, or adenocarcinoma? Findings This cohort study included 3689 patients with resectable gastric adenocarcinoma, gastric neuroendocrine carcinoma, or gastric mixed adenoneuroendocrine carcinoma. Propensity score matching analysis found that, compared with gastric adenocarcinoma, gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma were independent risk factors associated with worse disease-free survival, postrecurrence survival, and distant recurrence outcomes. Meaning These findings suggest that different follow-up and treatment strategies should be developed to improve the long-term survival of patients with gastric neuroendocrine carcinoma or gastric mixed adenoneuroendocrine carcinoma, especially for patients with tumors penetrating into the subserosa or deeper layers and with lymph node metastasis., This cohort study examines differences in long-term survival and patterns of recurrence among patients with gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma., Importance Gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma are rare pathological types of gastric cancer, and there is a lack of multicenter studies comparing the prognosis and recurrence patterns of gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Objective To compare the differences in long-term survival and patterns of recurrence among gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Design, Setting, and Participants This cohort study included patients with resectable gastric neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma at 23 hospitals in China from January 2006 to December 2016. In addition, patients with gastric adenocarcinoma were selected as controls. Propensity score–matched analysis was used to match pathological stage among the different pathological types, and disease-free survival (DFS), postrecurrence survival (PRS), and patterns of recurrence were examined. Data analysis was conducted from July 15, 2020, to October 21, 2020. Exposures Curative resection for gastric neuroendocrine carcinoma, gastric mixed adenoneuroendocrine carcinoma, and gastric adenocarcinoma. Main Outcomes and Measures The main outcomes were DFS and patterns of recurrence. Results A total of 3689 patients were analyzed (median [interquartile range] age, 62 [55-69] years; 2748 [74.5%] men), including 503 patients (13.6%) with gastric neuroendocrine carcinoma, 401 patients (10.9%) with gastric mixed adenoneuroendocrine carcinoma, and 2785 patients (75.5%) with gastric adenocarcinoma. After propensity score matching, 5-year DFS was 47.6% (95% CI, 42.7%-52.5%) for patients with gastric neuroendocrine carcinoma, compared with 57.6% (95% CI, 55.1%-60.1%) with gastric adenocarcinoma (P

BackgroundHypoxia is one driving factor of gastric cancer. It causes a series of immunosuppressive processes and malignant cell responses, leading to a poor prognosis. It is clinically important to identify the molecular markers related to hypoxia.MethodsWe screened the prognostic markers related to hypoxia in The Cancer Genome Atlas database, and a risk score model was developed based on these markers. The relationships between the risk score and tumor immune microenvironment were investigated. An independent validation cohort from Gene Expression Omnibus was applied to validate the results. A nomogram of risk score model and clinicopathological factor was developed to individually predict the prognosis.ResultsWe developed a hypoxia risk score model based on SERPINE1 and EFNA3. Quantified real-time PCR was further applied to verified gene expressions of SERPINE1 and EFNA3 in gastric cancer patients and cell lines. A high-risk score is associated with a poor prognosis through the immunosuppressive microenvironment and immune escape mechanisms, including infiltration of immunosuppressive cells, expression of immune checkpoint molecules, and enrichment of signal pathways related to cancer and immunosuppression. The nomogram basing on the hypoxia-related risk score model showed a good ability to predict prognosis and high clinical net benefits.ConclusionsThe hypoxia risk score model revealed a close relationship between hypoxia and tumor immune microenvironment. The current study potentially provides new insights of how hypoxia affects the prognosis, and may provide a new therapeutic target for patients with gastric cancer.

Purpose:Lung metastasis is an important cause of breast cancer–related deaths, in which SDF-1/CXCR4 signaling pathway plays a critical role. Single transmembrane protein LRP6 is viewed as an oncogene via activating the Wnt/β-catenin signaling pathway. Our work aims to investigate the relationship between SDF-1/CXCR4 and LRP6 in breast cancer lung metastasis.Experimental Design:We examined the expressions and functions of SDF-1/CXCR4 and LRP6 as well as their relationship in breast cancer in vitro and in vivo.Results:LRP6 ectodomain (LRP6N) directly bound to CXCR4 and competitively prevented SDF-1 binding to CXCR4. LRP6N prevented SDF-1/CXCR4-induced metastasis to lung and prolonged survival in mice bearing breast tumors, whereas LRP6 knockdown activated SDF-1/CXCR4 signal transduction and promoted lung metastasis and tumor death. Furthermore, patients with breast cancer with high CXCR4 expression had poor prognosis, which was exacerbated by low LRP6 expression but improved by high LRP6 expression. Interestingly, a secreted LRP6N was found in the serum of mice and humans, which was downregulated by the onset of cancer metastasis in both mice bearing breast cancer as well as in patients with breast cancer.Conclusions:LRP6N might be a promising diagnostic marker for the early detection of breast cancer metastasis as well as an inhibitor of SDF-1/CXCR4-induced breast cancer metastasis. LRP6N also provides an interesting link between Wnt signaling and SDF-1/CXCR4 signaling, the two key pathways involved in cancer development.

The aim of this study was to evaluate the prognostic value of the eighth AJCC TNM staging classification for patients with gastric cancer who had already survived for 5 years.Patients who underwent radical gastrectomy at a large eastern center were considered. The prognostic value of staging systems were assessed and compared. Additional external validation was performed using a dataset from the Surveillance, Epidemiology, and End Result (SEER) database.The 5-year overall survival (OS) rate for patients in the training set was 59.4%. With the prolongation of the survival time after surgery, the 5-year OS improved significantly (P 0.05). However, there were no significant differences in survival curves among patients who have survived 5 years after surgery. The AUC and χ2 of the eighth AJCC classification for predicting of 5-year OS decreased gradually after surgery and appeared stable after 5 years. For patients who survived 5 years after surgery, we constructed a new TNM staging system (nTNM) according to the survival curves of T stage and N stage. A 2-step multivariate analysis showed that nTNM, age and sex were independent prognostic factors. The nTNM demonstrated superior prognostic stratification, with higher c-statistic and likelihood ratio chi-square scores and lower AIC values than those of the AJCC classification. Similar results were observed in the external validation set.The nTNM predicted an additional survival more accurately than did the AJCC classification for patients who have survived 5 years after surgery; this may guide decisions regarding surveillance.

Increased macrophage phagocytosis of antibody-coated platelets, as well as decreased numbers and/or impaired function of CD4+CD25+Foxp3+ regulatory T (Treg) cells, has been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Low-dose histone deacetylase inhibitors (HDACi’s) are anti-inflammatory and immunomodulatory agents that can enhance immunosuppression in graft-versus-host disease by increasing the number and function of Foxp3+ Treg cells, but it is unclear whether they have the potential to promote immune tolerance and platelet release in ITP. In this study, we performed in vitro and in vivo experiments and found that a low-dose HDACi (chidamide) alleviated thrombocytopenia in passive and active murine models of ITP. Further, low-dose HDACi’s attenuated macrophage phagocytosis of antibody-coated platelets, stimulated the production of natural Foxp3+ Treg cells, promoted the peripheral conversion of T cells into Treg cells, and restored Treg cell suppression in vivo and in vitro. Finally, we confirmed that low-dose HDACi’s could regulate CTLA4 expression in peripheral blood mononuclear cells through modulation of histone H3K27 acetylation. Low-dose HDACi treatment in ITP could be offset by blocking the effect of CTLA4. Therefore, we propose that low-dose chidamide administration has potential as a novel treatment for ITP in the clinic.

AIM To establish an appropriate N classification system for early gastric cancer (EGC). METHODS Data from 10714 patients who underwent radical gastrectomy between 1988 and 2011 were retrieved from the National Cancer Institute’s Surveillance, Epidemiology, and End Result database. The overall survival (OS) based on the eighth edition and new tumor lymph node metastasis (TNM) staging systems were compared, and the analysis was repeated in an external validation set from the Fujian Medical University Union Hospital database. RESULTS There were no significant differences in OS between N1 and N2 cancers or between N3a and N3b cancers in cases of EGC. The X-tile program identified that the new staging system for EGC consisted of T1N0, T1N1’ [1-6 metastatic lymph nodes (LNs)], and T1N2’ ( ≥ 7 metastatic LNs). Compared with the eighth edition of the TNM staging system, the OS of patients in T1N1’ stage was similar to that of patients with stage IIA disease, whereas the OS of patients in T1N2’ stage was similar to that of patients with stage IIB disease. The new TNM staging system exhibited a slightly lower Akaike Information Criterion value and higher χ2 and c-statistic compared with the eighth edition of the TNM classification system. Similar results were found in the external validation dataset from the external validation set. CONCLUSION We have developed an optional new TNM staging system with a better predictive ability that can be used to accurately predict the 5-year OS of patients with EGC.

Disseminated intravascular coagulation (DIC) is a severe complication of critical conditions. There are several scoring systems used for the diagnosis of DIC, including the International Society on Thrombosis and Hemostasis (ISTH) Overt-DIC criteria, the Japanese Ministry of Health and Welfare (JMHW) criteria and the Chinese Society of Thrombosis and Hemostasis scoring system for DIC (CDSS). The objective of this prospective study was to evaluate the accuracy and predictive value of the CDSS.1318 patients, aged 18-70 years old and suspected of DIC were enrolled from 18 hospitals across China. Participants were divided into two groups for analysis (group 1, non-hematological diseases; group 2, hematological diseases). 242 patients were excluded because of incomplete data collection and failure to follow-up.The rates of concordance of diagnosis of DIC between the CDSS and two other scoring systems were close to 80%. The area under ROC curves of CDSS had a slight advantage when using the ISTH, JMHW criteria or prognosis as gold standard, respectively. The CDSS DIC was an independent predictor of mortality, and its odds-ratio was superior or comparable to that of the ISTH and JMHW criteria in the two groups. The CDSS DIC score also had a significant correlation with the APACHE II and SOFA score (p 0.05). In summary, as a quantification standard of the Chinese experts' consensus, the CDSS is conducive to the standardized diagnosis of DIC because of its favorable diagnostic and prognostic utility.

Background The American Joint Committee on Cancer 8th classification states that colorectal cancer (CRC) is classified as N1c stage when regional lymph nodes (LNs) are negative and tumor deposits (TDs) are positive. However, how to classify TDs when regional LNs are positive remains unclear. The current study aimed to investigate the possibility of combining positive LNs and positive TDs to develop a modified pathological N (mpN) stage for CRC. Methods We retrospectively analyzed 9,198 patients with stage III CRC from the Surveillance, Epidemiology, and End Results program who underwent surgery (6,440 in the training cohort and 2,758 the validation cohort). The combination of positive LNs and TD status was defined as mpN stage. Overall survival (OS) according to mpN and pathological N (pN) stages was analyzed by the Kaplan-Meier method. The area under the curves (AUCs) and Akaike's information criterion (AIC) were applied to assess the predictive discrimination abilities and goodness-of-fit of the model. The clinical benefits were measured using decision curve analyses. The validation cohort was used to validate the results. Results AUC analysis showed that the prognostic discrimination of mpN stage (AUC = 0.628, 95% confidence interval (CI), 0.616-0.640) was better than that of pN stage (AUC = 0.618, 95% CI, 0.606-0.630, p = 0.006) for OS. The AIC demonstrated that mpN stage (AIC = 30,217) also showed superior model-fitting compared with pN stage (AIC = 30,257) and decision curve analyses revealed that mpN stage had better clinical benefits than pN stage. Similar results were found in the validation cohort. Conclusions Among patients with CRC and LN metastasis, mpN stage might be superior to pN stage for assessing prognosis and survival, suggesting that TD status should be included in the pN stage.

Background: The tumor-node-metastasis classification of the American Joint Committee on Cancer classified tumor deposits (TDs) in patients with colorectal cancer (CRC) without lymph node (LN) metastasis as N1c, but the classification of TDs in patients with LN metastases remains controversial. This study investigated the probability of regarding TDs as positive LNs (pLNs) in pN stage and estimated its prognostic ability in CRC. Methods: We used the Surveillance, Epidemiology, and End Results program to analyze CRC patients who underwent surgical therapy (14,906 training cohort, 6,384 validation cohort). A modified pN stage (mpN) was identified using the number of pLNs plus TDs. Overall survival (OS) was analyzed using the Kaplan–Meier survival curves, and significant prognostic factors were identified by univariate and multivariate analyses. Prognostic ability was estimated using the area under the curve (AUC), calibration curve, and the Akaike's information criterion (AIC). Clinical benefit was measured by the decision curve analyses (DCA). The results were validated using the validation cohort. Results: Both the pN and mpN stages were independent prognostic factors in CRC according to univariate and multivariate analyses. The AUC analysis showed that the mpN stage had better prognostic discrimination for OS than the pN stage (0.612 vs. 0.605, P < 0.001). The AIC demonstrated that the mpN stage also showed superior model-fitting compared with the pN stage (49,756 vs. 49,841). The DCA further revealed that the mpN stage had better clinical benefits than the pN stage. The validation cohort showed similar findings. Conclusions: We concluded that counting TDs as pLNs may be superior to the pN stage when assessing the prognosis of CRC patients.

Background The American Joint Committee on Cancer (AJCC) 8th tumor-node-metastasis (TNM) classification for colorectal cancer (CRC) has limited ability to predict prognosis. Methods We included 45 379 eligible stage I-III CRC patients from the Surveillance, Epidemiology, and End Results Program. Patients were randomly assigned individually to a training (n = 31 772) or an internal validation cohort (n = 13 607). External validation was performed in 10 902 additional patients. Patients were divided according to T and N stage permutations. Survival analyses were conducted by a Cox proportional hazard model and Kaplan-Meier analysis, with T1N0 as the reference. Area under receiver operating characteristic curve and Akaike information criteria were applied for prognostic discrimination and model fitting, respectively. Clinical benefits were further assessed by decision curve analyses. Results We created a modified TNM (mTNM) classification: stages I (T1-2N0-1a); IIA (T1N1b, T2N1b, T3N0); IIB (T1-2N2a-2b, T3N1a-1b, T4aN0); IIC (T3N2a, T4aN1a-2a, T4bN0); IIIA (T3N2b, T4bN1a); IIIB (T4aN2b, T4bN1b); and IIIC (T4bN2a-2b). In the internal validation cohort, compared with the AJCC 8th TNM classification, the mTNM classification showed superior prognostic discrimination (area under receiver operating characteristic curve = 0.675 vs 0.667, respectively; 2-sided P Conclusions The mTNM classification provides better prognostic discrimination than AJCC 8th TNM classification, with good applicability in various populations and settings, to help better stratify stage I-III CRC patients into prognostic groups.

A physiologically relevant glioma tumor model is important to the study of disease progression and screening drug candidates. However, current preclinical glioma models lack the brain microenvironment, and the established tumor cell lines do not represent glioma biology and cannot be used to evaluate the therapeutic effect. Here, we reported a real-time integrated system by generating 3D ex vivo cerebral organoids and in vivo xenograft tumors based on glioma patient-derived tissues and cells. Our system faithfully recapitulated the histological features, response to chemotherapy drugs, and clinical progression of their corresponding parental tumors. Additionally, our model successfully identified a case from a grade II astrocytoma patient with typical grade IV GBM features in both organoids and xenograft models, which mimicked the disease progression of this patient. Further genomic and transcriptomic characterization was associated with individual clinical features. We have demonstrated the "GBM-&Normal-like" signature to predict prognosis. In conclusion, we developed an integrated system of parallel models from patient-derived glioma cerebral organoids and xenografts for understanding the glioma biology and prediction of response to chemotherapy drugs, which might lead to a new strategy for personalized treatment for this deadly disease.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979

Background It has previously been shown that bevacizumab, when added to chemotherapy, improved overall survival in several cancers. In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival and it is widely used for tumor recurrence, though it has failed to improve overall survival (OS) in controlled trials. However, an effective biomarker for predicting the prognosis of bevacizumab treatment has yet to be identified. This study, therefore, aimed to retrospectively analyze the polymorphisms of p53 codon 72 and the clinical characteristics of GBM specimens from Taiwanese patients. Methods The polymorphisms of p53 codon 72 in 99 patients with GBM treated at Taichung Veterans General Hospital in Taiwan from 2007 to 2017 were analyzed using direct DNA sequencing and PCR-RFLP analysis. Results We found that among these GBM patients, the distribution of codon 72 polymorphisms was 28.3% for proline homozygotes (Pro/Pro), 38.4% for arginine homozygotes (Arg/Arg), and 33.3% for proline/arginine heterozygotes (Pro/Arg). Although the polymorphisms of p53 codon 72 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Pro genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone. Conclusions This pilot study suggests that both the Arg/Arg and Arg/Pro genotypes of p53 codon 72 polymorphism may have value as independent prognostic or predictive parameters for bevacizumab treatment response and failure. Relatedly, the results of the study further demonstrate the utility of stratifying GBM patients according to bevacizumab sensitivity.

Background: This study aimed to develop an effective prognostic nomogram for predicting non-metastatic colon cancer. Methods: The Surveillance, Epidemiology, and End Results program was utilized to analyze patients who underwent surgical therapy (25,350 for training, 10,860 for validation). Nomograms were created depending upon multivariate analysis in the training cohort and were compared to current American Joint Committee on Cancer (AJCC) classifications. Areas under the receiver-operating characteristic curves (AUCs), Akaike's information criterions (AICs), and calibration curves were used. The clinical benefit was measured using decision curve analyses (DCAs). The validation cohort was used to validate the results. Results: Nomogram 1 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and N stage. Nomogram 2 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and number of positive lymph nodes. The prognostic discrimination of nomogram 1 (AUC, 0.729, 95% CI, 0.723-0.736) was better than that of nomogram 2 (AUC, 0.704, 95% CI, 0.698-0.710, p < 0.001) in five-year overall survival in the training cohort. Nomogram 1 (AIC, 137,319) also showed superior model-fitting compared to nomogram 2 (AIC, 137,453). Similarity, nomogram 1 was better than the AJCC 6th and 8th TNM classifications. DCA revealed that nomogram 1 had a superior net benefit than other models. These findings were validated using the validation cohort. Conclusions: The proposed nomogram 1 was a better prognostic prediction model with better discrimination and superior model-fitting for patients with non-metastatic colon cancer, which might prove to be clinically helpful.

Background Gastric cancer (GC) is one of the most common aggressive cancers and is characterized by high mortality. Increasing evidence has shown that microRNA-665 (miRNA-665) serves as inhibiting-miRNA in cancers. However, the role of miR-665 in GC is yet unclear. Methods miR-665 was first analyzed using bioinformatics. Subsequent quantitative real-time PCR was used to detect miR-665 expression levels in different GC cell lines and tissues. The function of miR-665 in GC cells was determined via Cell Counting Kit 8, colony formation, wound healing, and transwell assays. Furthermore, Western blotting was utilized to measure the expression level of epithelial–mesenchymal transition (EMT)-related proteins. The target prediction and luciferase reporter assays were performed to confirm the binding between miR-665 and 3ʹ-UTR of the CRIM1 gene. In addition, rescue assays were used to determine whether CRIM1 upregulation abolished the inhibitory effect of miR-665. Results The expression of miR-665 was significantly decreased in GC patients and GC cell lines. Clinical and pathological analyses showed that the low expression of miR-665 was significantly associated with high TNM stage (P = 0.007), distant metastasis (P = 0.031), and poor differentiation (P = 0.029). Endogenic mimics of miR-665 remarkably suppressed GC cell proliferation, migration, invasion, and EMT in in vitro experiments. Inhibition of miR-665 expression induced the opposite effects. The results of the bioinformatics analysis and dual-luciferase assay showed that miR-665 targeted the 3ʹ-UTR of the CRIM1 gene. Rescue assays revealed that overexpression of CRIM1 attenuated the inhibitory effects of miR-665 in GC progression and EMT. Conclusion The overall study results demonstrated that miR-665 inhibits tumor progression and EMT in GC by targeting CRIM1, indicating that miR-665 might be a potential therapeutic target in the treatment of GC patients.

A previous study confirmed that a novel splicing variant of large vascular endothelial growth factor (L-VEGF) termed L-VEGF144, a nucleolus protein, is found in glioblastoma cells and specimens, but the actual biological function and clinical significance of L-VEGF144 remain unclear. In this study, we analyzed the expression of L-VEGF144 in 68 glioblastoma multiforme specimens using reverse transcriptase-polymerase chain reaction analysis. The results showed that the high expression of L-VEGF144 was associated with a poor prognosis in the bevacizumab plus concurrent chemoradiotherapy with temozolomide treatment. In addition, we constructed a series truncated and mutant form of L-VEGF144 to confirm that exon 6a of L-VEGF144 is able to engage in the nuclear importation and found that 8 lysines within exon 6a play a critical role in the nucleolus aggregation of L-VEGF144. Also, the transfection of the L-VEGF144 increased the number of nucleoli. Furthermore, the recombinant protein Flag-L-VEGF144 and commercial VEGF protein have similar growth stimulatory activities in terms of inducing glioblastoma cell proliferation in vitro. Taken together, these results indicated that the expression of L-VEGF144 could potentially serve as an independent indicator of poor prognosis in bevacizumab treatment.

Background: Familial hypercholesterolemia (FH) has been associated with early coronary artery disease (CAD) and increased risk of atherosclerotic cardiovascular disease. However, the prevalence of FH and its long-term outcomes in a CAD-high-risk cohort, defined as patients with hypercholesteremia who underwent coronary angiography, remains unknown. Besides, studies regarding the impact of genetic variations in FH on long-term cardiovascular (CV) outcomes are scarce. Methods and Results: In total, 285 patients hospitalized for coronary angiography with blood low-density lipoprotein cholesterol (LDL-C) levels ≥ 160 mg/dL were sequenced to detect FH genetic variations in LDL receptors apolipoprotein B and proprotein convertase subtilisin/kexin type 9. Risk factors associated with long-term CV outcomes were evaluated. The prevalence of FH was high (14.4%). CAD and early CAD were significantly more prevalent among FH variation carriers than non-carriers, despite comparable blood LDL-C levels. Moreover, the FH variation carriers also underwent more revascularization after a mean follow-up of 6.1 years. Multivariate logistic regression demonstrated that FH genetic variation was associated with increased incidence of cardiovascular disease and mortality (odds ratio = 3.17, p = 0.047). Two common FH variants, LDLR c.986G&gt, A and LDLR c.268G&gt, A, showed the most significant impacts on high blood LDL-C levels and early-onset CAD. Conclusions: Our results indicate that FH genetic variants may exhibit differential effects on early-onset CAD and revascularization risks in patients undergoing coronary angiography. FH genetic information might help identify high-risk patients with typical CAD symptoms for appropriate intervention.

Objective MicroRNA (miR)-93 has been proven to mediate the initiation and progression of colorectal carcinoma (CRC); however, the mechanisms by which miR-93 mediates CRC development need deeper elucidation. The present study is designed to investigate the association between miR-93 and high mobility group box 3 (HMGB3), as well as the functions of miR-93, in CRC. Methods miR-93 expression was quantified by RT-qPCR. CRC cells were transfected or cotransfected with miR-93 mimic, miR-93 inhibitor, pcDNA3.1-HMGB3 and sh-HMGB3, and then the proliferative, migratory and invasive capacities were detected in addition to the apoptotic rate. Western blotting assessed the expression levels of HMGB3, PI3K, p-PI3K, AKT and p-AKT. The interaction between miR-93 and HMGB3 was identified. Results In CRC tissues, miR-93 was downregulated and HMGB3 was upregulated. LOVO and SW480 cells transfected with miR-93 mimic exhibited reduced proliferation, invasion and migration as well as increased apoptosis. The ratios of p-PI3K/PI3K and p-AKT/AKT were declined after miR-93 mimic was introduced into the CRC cell lines. miR-93 negatively downregulated HMGB3, and introduction of pcDNA3,1-HMGB3 could counteract, in part, the inhibitory effects of miR-93 on the malignant properties of CRC cells as well as the ratios of p-PI3K/PI3K and p-AKT/AKT. Conclusion miR-93 targeted HMGB3 to block the activation of the PI3K/AKT pathway and thus enhance CRC cell apoptosis.

Utidelone, a genetically engineered epothilone analogue, has shown promise as a potential treatment for breast cancer in phase 1 and 2 trials. The aim of this phase 3 trial was to compare the efficacy and safety of utidelone plus capecitabine versus capecitabine alone in patients with metastatic breast cancer.We did a multicentre, open-label, superiority, phase 3, randomised controlled trial in 26 hospitals in China. Eligible participants were female patients with metastatic breast cancer refractory to anthracycline and taxane chemotherapy regimens. We randomly assigned participants (2:1) using computer based randomisation and block sizes of 6 to a 21-day cycle of either utidelone (30 mg/mBetween Aug 8, 2014, and Dec 14, 2015, we enrolled and randomly assigned 270 patients to treatment with utidelone plus capecitabine, and 135 to capecitabine alone. Median follow-up for progression-free survival was 6·77 months (IQR 3·81-10·32) for the utidelone plus capecitabine group and 4·55 months (2·55-9·39) for the capecitabine alone group. Median progression-free survival by central review in the utidelone plus capecitabine group was 8·44 months (95% CI 7·95-9·92) compared with 4·27 months (3·22-5·68) in the capecitabine alone group; hazard ratio 0·46, 95% CI 0·36-0·59; p0·0001. Peripheral neuropathy was the most common grade 3 adverse event in the utidelone plus capecitabine group (58 [22%] of 267 patients vs 1 [1%] of 130 patients in the capecitabine alone group). Palmar-plantar erythrodysaesthesia was the most prominent grade 3 adverse event in the capacitabine alone group (in 10 [8%] of 130 patients) and was the next most frequent grade 3 event in the utidelone plus capecitabine group (in 18 [7%] of 267 patients). 16 serious adverse events were reported in the combination therapy group (diarrhoea was the most common, in three [1%] patients) and 14 serious adverse events were reported in the monotherapy group (the most common were diarrhoea, increased blood bilirubin, and anaemia, in two [2%] patients for each event). 155 patients died (99 in the combination therapy arm, 56 in the monotherapy arm). All deaths were related to disease progression except for one in each group (attributed to pericardial effusion in the combination therapy group and dyspnoea in the monotherapy group) that were considered possibly or probably treatment-related.Despite disease progression with previous chemotherapies, utidelone plus capecitabine was more efficacious compared with capecitabine alone for the outcome of progression-free survival, with mild toxicity except for peripheral sensory neuropathy, which was manageable. The findings from this study support the use of utidelone plus capecitabine as an effective option for patients with metastatic breast cancer.Beijing Biostar Technologies, Beijing, China.

Background We sought to investigate the prognostic value of complete blood count (CBC)-based biomarkers for patients with resectable gastric cancer (GC). Methods Patients with GC who underwent primary surgical resection between December 2008 and December 2013 were included. The estimated area under the curve (AUC) and multivariate Cox regression models were used to identify the best CBC-based biomarker. Time-dependent receiver operating characteristic (t-ROC) curve analysis was used to predict overall survival and compare the prognostic impact. Results In the 1810 patients analyzed, the median follow-up period was 51.0 months (range 1–101 months). Based on multivariate analysis, the lymphocyte-monocyte ratio (LMR) and hemoglobin (Hb) level were independent prognostic factors (both P P Conclusion The preoperative LMR and Hb level were optimal CBC-based biomarkers for predicting OS in GC patients after curative resection. Based on the LMR and Hb, we developed a novel and easily obtainable prognostic score called the CBCS, which may improve the prediction of clinical outcomes.

Previous studies have suggested that preoperative anemia negatively influences survival in patients with gastric cancer (GC). We sought to investigate which anemic markers can better predict the prognosis of patients with resectable GC. The study involved 2277 GC patients who underwent curative resection between December 2008 and December 2014. Cox regression models were used to identify the best anemic markers associated with prognosis. Time-dependent receiver operating characteristics analysis (t-ROC) and the estimated area under the curve (AUC) were used to compare the prognostic values. Of all patients, 1709 (75.1%) were male, and the median age was 61 years. Univariate analyses showed that preoperative hematocrit (HCT), hemoglobin, and mean corpuscular volume were associated with OS (all P

The no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI) can lead to poor outcomes. Increased neutrophil counts have been associated with an increased risk of adverse clinical events after acute myocardial infarction (AMI). The aim of this study was to assess the relation between admission neutrophil counts and angiographic no-reflow after PPCI.A total of 217 patients with acute STEMI who underwent PPCI, were enrolled. The patients were divided into two groups: no-reflow and normal-reflow. The neutrophil counts and other laboratory parameters were measured on admission before PPCI.There were 41 patients (18.9%) in the no-reflow group and 176 patients in the normal-reflow group. Patients with no-reflow were older (68.0 ± 11.7 years vs 60.7 ± 13.2 years, P = 0.019) and had significantly higher admission neutrophil counts (9.02 ± 3.97 × 109/L vs 7.57 ± 2.82 × 109/L, P = 0.007). Also, high-sensitivity C-reactive protein (hsCRP), white blood counts, monocyte counts were significantly higher while haemoglobin values were significantly lower in the no-reflow group. In multivariate analysis, neutrophil counts remained a strong independent predictor of angiographic no-reflow (odds ratio 1,200, 95% confidence interval 1.073-1.342, P = 0.001) together with age (odds ratio 1.041, 95% confidence interval 1.012-1.071, P = 0.005).Neutrophil counts on admission and age were independent clinical predictors of no-reflow following primary PCI in patients with STEMI. Our findings suggest that admission neutrophil counts may be available for early risk stratification of no-reflow after primary PCI and might allow the improvement of strategies to prevent this phenomenon.

To evaluate whether the serum thrombopoietin levels in pregnancy-associated immune thrombocytopenia (ITP) differ from those in gestational thrombocytopenia, and reveal the possibility of thrombopoietin serving as a marker for differential diagnosis. Serum thrombopoietin concentration was determined in ITP in pregnancy (n = 35), gestational thrombocytopenia (n = 31), healthy pregnancy (n = 32), age-matched nonpregnant ITP (n = 32) and nonpregnant healthy controls (n = 35) by ELISA. The serum thrombopoietin level of ITP in pregnancy (1283 ± 646 pg/mL) was significantly higher than gestational thrombocytopenia (187 ± 64 pg/mL) (P < 0.01), although the platelet counts of these two disorders may overlap. Twenty-nine of 35 patients with ITP in pregnancy had thrombopoietin values >500 pg/mL, whereas none of the gestational thrombocytopenia patients' thrombopoietin levels exceeded 500 pg/mL. In addition, ITP in pregnancy presented a markedly higher thrombopoietin level than nonpregnant ITP (88 ± 41 pg/mL) (P < 0.01), indicating that the pathogenesis of pregnant and nonpregnant ITP was different. Our findings suggest that measurement of serum thrombopoietin concentration provides valuable diagnostic information for differentiating ITP in pregnancy from gestational thrombocytopenia. Thrombopoietin represents a reliable marker for ITP in pregnancy.

// Tao Qin 1,* , Yin-duo Zeng 1,2,* , Ge Qin 1,* , Fei Xu 1,* , Jia-bin Lu 1 , Wen-feng Fang 1 , Cong Xue 1 , Jian-hua Zhan 1 , Xin-ke Zhang 1 , Qiu-fan Zheng 1 , Rou-jun Peng 1 , Zhong-yu Yuan 1 , Li Zhang 1 and Shu-sen Wang 1 1 Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, P. R. China 2 Sun Yat-sen University Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, P. R. China * These authors have contributed equally to this work Correspondence to: Shu-sen Wang, email: // Li Zhang, email: // Zhong-yu Yuan, email: // Keywords : PD-L1, breast cancer, ER, PR, prognosis, nomogram Received : July 07, 2015 Accepted : August 22, 2015 Published : September 10, 2015 Abstract Background: To investigate the role of PD-L1 expression in tumor recurrence and metastasis in Chinese patients with breast cancer. Methods: Suitable tissue samples were available from 870 patients with breast cancer. Paraffin-embedded tumor sections were stained with PD-L1 antibody. The correlations between PD-L1 expression and clinical characteristics, ER/PR/HER2 status and survival parameters were analyzed. Kaplan-Meier and univariate Cox proportional hazards model analyses were used to compare the survival of patients with high PD-L1 expression and patients with no PD-L1 expression. Results: The median follow-up time was 98 months(range, 17–265 months).The positive rate of PD-L1 expression in breast cancer was 21.7% (189/870). PD-L1 high expression was inversely associated with larger tumor size, higher tumor grade, more positive lymph node number, as well as negative ER and PR status. PD-L1 expression was particularly higher in TNBC compared with non-TNBC, although no statistical significance was observed. Nomogram logistic regression results based on clinical and pathological features showed that the following factors were more likely associated with high PD-L1 expression: patient age younger than 35 years, larger tumor size, lymphovascular invasion and advanced stage. Our data indicated that patients with high PD-L1 expression had poor DFS, DMFS and overall survival compared with those with no PD-L1 expression. Univariate Cox proportional hazards model analysis showed that PD-L1 was an independent prognostic factor for tumor prognosis. Conclusions: PD-L1 expression is an important indicator of unfavorable prognosis in breast cancer patients.