Long Noncoding RNA MSL3P1 Regulates CUL3 mRNA Cytoplasmic Transport and Stability and Promotes Lung Adenocarcinoma Metastasis.

Lung adenocarcinoma (LUAD) is the most prevalent histological type of lung cancer. Previous studies have reported that specific long noncoding RNAs (lncRNA) are involved in cancer development and progression. The phenotype and mechanism of ENST00000440028, named MSL3P1, an lncRNA referred to as a cancer-testis gene with potential roles in tumorigenesis and progression, have not been reported. MSL3P1 is overexpressed in LUAD tumor tissues, which is significantly associated with clinical characteristics, metastasis, and poor clinical prognosis. MSL3P1 promotes the metastasis of LUAD in vitro and in vivo. The enhancer reprogramming in LUAD tumor tissue is the major driver of the aberrant expression of MSL3P1. Mechanistically, owing to the competitive binding to CUL3 mRNA with ZFC3H1 protein (a protein involved in targeting polyadenylated RNA to exosomes and promoting the degradation of target mRNA), MSL3P1 can prevent the ZFC3H1-mediated RNA degradation of CUL3 mRNA and transport it to the cytoplasm. This activates the downstream epithelial-to-mesenchymal transition signaling pathway and promotes tumor invasion and metastasis. Implications: This study indicates that lncRNA MSL3P1 regulates CUL3 mRNA stability and promotes metastasis and holds potential as a prognostic biomarker and therapeutic target in LUAD.

A liquid biopsy assay for the noninvasive detection of lymph node metastases in T1 lung adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma (LUAD) is a common pathological type of lung cancer. The presence of lymph node metastasis plays a crucial role in determining the overall treatment approach and long-term prognosis for early LUAD, therefore accurate prediction of lymph node metastasis is essential to guide treatment decisions and ultimately improve patient outcomes. METHODS: We performed transcriptome sequencing on T1 LUAD patients with positive or negative lymph node metastases and combined this data with The Cancer Genome Atlas Program cohort to identify potential risk molecules at the tissue level. Subsequently, by detecting the expression of these risk molecules by real-time quantitative PCR in serum samples, we developed a model to predict the risk of lymph node metastasis from a training cohort of 96 patients and a validation cohort of 158 patients. RESULTS: Through transcriptome sequencing analysis of tissue samples, we identified 11 RNA (miR-412, miR-219, miR-371, FOXC1, ID1, MMP13, COL11A1, PODXL2, CXCL13, SPOCK1 and MECOM) associated with positive lymph node metastases in T1 LUAD. As the expression of FOXC1 and COL11A1 was not detected in serum, we constructed a predictive model that accurately identifies patients with positive lymph node metastases using the remaining nine RNA molecules in the serum of T1 LUAD patients. In the training set, the model achieved an area under the curve (AUC) of 0.89, and in the validation set, the AUC was 0.91. CONCLUSIONS: We have established a new risk prediction model using serum samples from T1 LUAD patients, enabling noninvasive identification of those with positive lymph node metastases.

Dynamics of host immune responses and a potential function of Trem2hi interstitial macrophages in Pneumocystis pneumonia.

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening opportunistic fungal infection with a high mortality rate in immunocompromised patients, ranging from 20 to 80%. However, current understanding of the variation in host immune response against Pneumocystis across different timepoints is limited. METHODS: In this study, we conducted a time-resolved single-cell RNA sequencing analysis of CD45+ cells sorted from lung tissues of mice infected with Pneumocystis. The dynamically changes of the number, transcriptome and interaction of multiply immune cell subsets in the process of Pneumocystis pneumonia were identified according to bioinformatic analysis. Then, the accumulation of Trem2hi interstitial macrophages after Pneumocystis infection was verified by flow cytometry and immunofluorescence. We also investigate the role of Trem2 in resolving the Pneumocystis infection by depletion of Trem2 in mouse models. RESULTS: Our results characterized the CD45+ cell composition of lung in mice infected with Pneumocystis from 0 to 5 weeks, which revealed a dramatic reconstitution of myeloid compartments and an emergence of PCP-associated macrophage (PAM) following Pneumocystis infection. PAM was marked by the high expression of Trem2. We also predicted that PAMs were differentiated from Ly6C+ monocytes and interacted with effector CD4+ T cell subsets via multiple ligand and receptor pairs. Furthermore, we determine the surface markers of PAMs and validated the presence and expansion of Trem2hi interstitial macrophages in PCP by flow cytometry. PAMs secreted abundant pro-inflammation cytokines, including IL-6, TNF-α, GM-CSF, and IP-10. Moreover, PAMs inhibited the proliferation of T cells, and depletion of Trem2 in mouse lead to reduced fungal burden and decreased lung injury in PCP. CONCLUSION: Our study delineated the dynamic transcriptional changes in immune cells and suggests a role for PAMs in PCP, providing a framework for further investigation into PCP's cellular and molecular basis, which could provide a resource for further discovery of novel therapeutic targets.

Characterization of the alternative splicing landscape in lung adenocarcinoma reveals novel prognosis signature associated with B cells.

BACKGROUND: Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related death. Malignant pleural effusion (MPE) is a special microenvironment for lung cancer metastasis. Alternative splicing, which is regulated by splicing factors, affects the expression of most genes and influences carcinogenesis and metastasis. METHODS: mRNA-seq data and alternative splicing events in lung adenocarcinoma (LUAD) were obtained from The Cancer Genome Atlas (TCGA). A risk model was generated by Cox regression analyses and LASSO regression. Cell isolation and flow cytometry were used to identify B cells. RESULTS: We systematically analyzed the splicing factors, alternative splicing events, clinical characteristics, and immunologic features of LUAD in the TCGA cohort. A risk signature based on 23 alternative splicing events was established and identified as an independent prognosis factor in LUAD. Among all patients, the risk signature showed a better prognostic value in metastatic patients. By single-sample gene set enrichment analysis, we found that among tumor-infiltrating lymphocytes, B cells were most significantly correlated to the risk score. Furthermore, we investigated the classification and function of B cells in MPE, a metastatic microenvironment of LUAD, and found that regulatory B cells might participate in the regulation of the immune microenvironment of MPE through antigen presentation and promotion of regulatory T cell differentiation. CONCLUSIONS: We evaluated the prognostic value of alternative splicing events in LUAD and metastatic LUAD. We found that regulatory B cells had the function of antigen presentation, inhibited naïve T cells from differentiating into Th1 cells, and promoted Treg differentiation in LUAD patients with MPE.

Hepatocyte growth factor combined with adenosine deaminase as biomarker for diagnosis of tuberculous pleural effusion.

Background: The simple, rapid, and accurate diagnosis of tuberculous pleural effusion (TPE) remains difficult. This study aimed to determine the accuracy of hepatocyte growth factor (HGF) in the diagnosis of TPE. Methods: We quantified the expression of HGF, adenosine deaminase (ADA), and interferon gamma (IFN-γ) in pleural effusion (PE) in 97 TPE subjects and 116 non-TPE subjects using an enzyme-linked immunosorbent assay (ELISA) or a fully automatic biochemical analyzer. The diagnostic performance of these three biomarkers was evaluated using a receiver operating characteristic (ROC) curve of subjects by age and gender. Results: We discovered that the TPE group had much higher levels of HGF than the non-TPE group, regardless of age or gender, and that there was no statistically significant difference between the two groups' levels of HGF expression in peripheral plasma. In female TPE patients aged ≤65 years, the AUCs of TPE and non-TPE diagnosed by HGF, ADA or IFN-γ were 0.988, 0.964, and 0.827, respectively. HGF plus ADA had the highest diagnostic efficacy in female TPE patients aged ≤65 years. With HGF plus ADA having a cut-off value of 0.219 for distinguishing TPE from non-TPE, the area under the curve (AUC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV) were, respectively, 0.998 (95% confidence interval [CI], 0.993-1.000), 100 (95% CI, 89.997-100.000), 96.667 (95% CI, 82.783-99.916), 97.222 (95% CI, 83.594-99.586), and 100. Conclusion: This study confirmed that HGF plus ADA has high diagnostic efficacy in younger female TPE patients and has the potential to be an excellent biomarker.

Downregulation of AHNAK2 inhibits cell cycle of lung adenocarcinoma cells by interacting with RUVBL1.

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading cause of death among cancer diseases. The tumorigenic functions of AHNAK2 in LUAD have attracted more attention in recent years, while there are few studies which have reported its high molecular weight. METHODS: The mRNA-seq data of AHNAK2 and corresponding clinical data from UCSC Xena and GEO was analyzed. LUAD cell lines were transfected with sh-NC and sh-AHNAK2, and cell proliferation, migration and invasion were then detected by in vitro experiments. We performed RNA sequencing and mass spectrometry analysis to explore the downstream mechanism and interacting proteins of AHNAK2. Finally, western blot, cell cycle analysis and CO-IP were used to confirm our assumptions regarding previous experiments. RESULTS: Our study revealed that AHNAK2 expression was significantly higher in tumors than in normal lung tissues and higher AHNAK2 expression led to a poor prognosis, especially in patients with advanced tumors. AHNAK2 suppression via shRNA reduced the LUAD cell lines proliferation, migration and invasion and induced significant changes in DNA replication, NF-kappa B signaling pathway and cell cycle. AHNAK2 knockdown also caused G1/S phase cell cycle arrest, which could be attributed to the interaction of AHNAK2 and RUVBL1. In addition, the results from gene set enrichment analysis (GSEA) and RNA sequencing suggested that AHNAK2 probably plays a part in the mitotic cell cycle. CONCLUSION: AHNAK2 promotes proliferation, migration and invasion in LUAD and regulates the cell cycle via the interaction with RUVBL1. More studies of AHNAK2 are still needed to reveal its upstream mechanism.

Macrophage-derived exosome promotes regulatory T cell differentiation in malignant pleural effusion.

Introduction: Tumor-associated macrophages are one of the key components of the tumor microenvironment. The immunomodulatory activity and function of macrophages in malignant pleural effusion (MPE), a special tumor metastasis microenvironment, have not been clearly defined. Methods: MPE-based single-cell RNA sequencing data was used to characterize macrophages. Subsequently, the regulatory effect of macrophages and their secreted exosomes on T cells was verified by experiments. Next, miRNA microarray was used to analyze differentially expressed miRNAs in MPE and benign pleural effusion, and data from The Cancer Genome Atlas (TCGA) was used to evaluate the correlation between miRNAs and patient survival. Results: Single-cell RNA sequencing data showed macrophages were mainly M2 polarized in MPE and had higher exosome secretion function compared with those in blood. We found that exosomes released from macrophages could promote the differentiation of naïve T cells into Treg cells in MPE. We detected differential expression miRNAs in macrophage-derived exosomes between MPE and benign pleural effusion by miRNA microarray and found that miR-4443 was significantly overexpressed in MPE exosomes. Gene functional enrichment analysis showed that the target genes of miR-4443 were involved in the regulation of protein kinase B signaling and lipid biosynthetic process. Conclusions: Taken together, these results reveal that exosomes mediate the intercellular communication between macrophages and T cells, yielding an immunosuppressive environment for MPE. miR-4443 expressed by macrophages, but not total miR-4443, might serve as a prognostic marker in patients with metastatic lung cancer.

Correlation analysis between renal anatomical factors and residual stones after an ultrasound-guided PCNL.

Introduction: To predict the factors of residual stones after percutaneous nephrolithotomy (PCNL) by analyzing the characteristics of the renal anatomical structure in intravenous urography, so as to make a reasonable operation plan, reduce the risk of residual stones in PCNL, and improve the stone-free rate (SFR). Methods: A retrospective study was performed between January 2019 and September 2020 for patients treated with PCNL. According to the results of a kidney ureter bladder review after PCNL, 245 patients were divided into a residual stone group (71 patients, stone size >4 mm) and a stone-free group (174 patients, stone size ≤4 mm). An independent sample t-test was used to analyze the age, the length and width of channel calices, the angle between the channel calices and the involved calices, and the length and width of the involved calices. The gender, the channel types, the number of channels, the degree of hydronephrosis, and the number of involved calices were analyzed by using the chi-square test. A score of p < 0.05 was considered statistically significant. At the same time, logistic regression analysis was carried out to explore the independent influencing factors of the SFR after PCNL. Results: A total of 71 patients developed residual stones after surgery. The overall residual rate was 29.0%. The width of the channel calices (p = 0.003), the angle between the channel calices and the involved calices (p = 0.007), the width of the involved calices (p < 0.001), the channel types (p = 0.008), and the number of involved calices (p < 0.001) were all significantly correlated with residual stones after PCNL. Logistic regression analysis showed that the width of the channel calices (p = 0.003), the angle between the channel calices and the involved calices (p = 0.012), the width of the involved calices (p < 0.001), the channel types (p = 0.008), and the number of involved calyces (p < 0.001) were all independent influencing factors of the SFR after PCNL. Conclusion: A larger caliceal neck width and angle can reduce the risk of residual stones. The more calyces that are involved, the higher the risk of residual stones. There was no difference between F16 and F18, but F16 had a higher SFR than F24.

A comprehensive study of alternative splicing in malignant pleural mesothelioma identifies potential therapeutic targets in a new cluster with poor survival.

BACKGROUND: Malignant pleural mesothelioma (MPM) is one of the most aggressive tumors with few effective treatments worldwide. It has been suggested that alternative splicing at the transcriptome level plays an indispensable role in MPM. METHODS: We analyzed the splicing profile of 84 MPM patients from the TCGA cohort by using seven typical splicing types. We classified MPM patients based on their splicing status and conducted a comprehensive analysis of the correlation between the splicing classification and clinical characteristics, genetic variation, pathway changes, immune heterogeneity, and potential therapeutic targets. RESULTS: The expression of the alternative splicing regulator SRPK1 is significantly higher in MPM tissues than in normal tissues, and correlates with poor survival. SRPK1 deficiency promotes MPM cell apoptosis and inhibits cell migration in vitro. We divided the MPM patients into four clusters based on their splicing profile and identified two clusters associated with the shortest (cluster 3) and longest (cluster 4) survival time. We present the different gene signatures of each cluster that are related to survival and splicing. Comprehensive analysis of data from the GDSC and TCGA databases revealed that cluster 3 MPM patients could respond well to the small-molecule inhibitor CHIR-99021, a small-molecule inhibitor of GSK-3. CONCLUSION: We performed unsupervised clustering of alternative splicing data from 84 MPM patients from the TCGA database and identified a cluster associated with the worst prognosis that was sensitive to a GSK-3 inhibitor.

Interleukin 32 as a Potential Marker for Diagnosis of Tuberculous Pleural Effusion.

Accurate differential diagnosis is the key to choosing the correct treatment for pleural effusion. The present study aimed to assess whether interleukin 32 (IL-32) could be a new biomarker of tuberculous pleural effusion (TPE) and to explore the biological role of IL-32 in TPE. IL-32 levels were evaluated in the pleural effusions of 131 patients with undetermined pleural effusion from Wuhan and Beijing cohorts using an enzyme-linked immunosorbent assay method. Macrophages from TPE patients were transfected with IL-32-specific small interfering RNA (siRNA), and adenosine deaminase (ADA) expression was determined by real-time PCR and colorimetric methods. With a cutoff value of 247.9 ng/mL, the area under the curve of the receiver operating characteristic (ROC) curve for IL-32 was 0.933 for TPE, and the sensitivity and specificity were 88.4% and 93.4%, respectively. A multivariate logistic regression model with relatively good diagnostic performance was established. IL-32-specific siRNA downregulated ADA expression in macrophages, and IL-32γ treatment significantly induced ADA expression. Our results indicate that IL-32 in pleural effusion may be a novel biomarker for identifying patients with TPE. In addition, our multivariate model is acceptable to rule in or rule out TPE across diverse prevalence settings. Furthermore, IL-32 may modulate ADA expression in the tuberculosis microenvironment. (This study has been registered at ChiCTR under registration number ChiCTR2100051112 [https://www.chictr.org.cn/index.aspx].) IMPORTANCE Tuberculous pleural effusion (TPE) is a common form of extrapulmonary tuberculosis, with manifestations ranging from benign effusion with spontaneous absorption to effusion with pleural thickening, empyema, and even fibrosis, which can lead to a lasting impairment of lung function. Therefore, it is of great significance to find a rapid method to establish early diagnosis and apply antituberculosis therapy in the early stage. This study indicates that interleukin 32 (IL-32) in pleural effusion is a new high-potency marker to distinguish TPE from pleural effusions with other etiologies. A multivariate model combining age, adenosine deaminase (ADA), lactic dehydrogenase, and IL-32 may reliably rule in TPE in intermediate- or high-prevalence areas. Additionally, we observed that IL-32 might regulate ADA expression in macrophages in the tuberculosis microenvironment. Therefore, this study provides new insights into the role of IL-32 in the tuberculosis microenvironment.

Single-cell analysis of diverse immune phenotypes in malignant pleural effusion.

The complex interactions among different immune cells have important functions in the development of malignant pleural effusion (MPE). Here we perform single-cell RNA sequencing on 62,382 cells from MPE patients induced by non-small cell lung cancer to describe the composition, lineage, and functional states of infiltrating immune cells in MPE. Immune cells in MPE display a number of transcriptional signatures enriched for regulatory T cells, B cells, macrophages, and dendritic cells compared to corresponding counterparts in blood. Helper T, cytotoxic T, regulatory T, and T follicular helper cells express multiple immune checkpoints or costimulatory molecules. Cell-cell interaction analysis identifies regulatory B cells with more interactions with CD4+ T cells compared to CD8+ T cells. Macrophages are transcriptionally heterogeneous and conform to M2 polarization characteristics. In addition, immune cells in MPE show the general up-regulation of glycolytic pathways associated with the hypoxic microenvironment. These findings show a detailed atlas of immune cells in human MPE and enhance the understanding of potential diagnostic and therapeutic targets in advanced non-small cell lung cancer.

Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis.

Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients' survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.

Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction.

Adenocarcinoma at the gastroesophageal junction (ACGEJ) has dismal clinical outcomes, and there are currently few specific effective therapies because of limited knowledge on its genomic and transcriptomic alterations. The present study investigates genomic and transcriptomic changes in ACGEJ from Chinese patients and analyzes their drug vulnerabilities and associations with the survival time. Here we show that the major genomic changes of Chinese ACGEJ patients are chromosome instability promoted tumorigenic focal copy-number variations and COSMIC Signature 17-featured single nucleotide variations. We provide a comprehensive profile of genetic changes that are potentially vulnerable to existing therapeutic agents and identify Signature 17-correlated IFN-α response pathway as a prognostic marker that might have practical value for clinical prognosis of ACGEJ. These findings further our understanding on the molecular biology of ACGEJ and may help develop more effective therapeutic strategies.

[Level of Coagulation Function Indexes and Its Clinical Significance in Patients with Lymphoplasmacytic Lymphoma].

OBJECTIVE: To analyze the level of coagulation function indexes in patients with lymphoplasmacytic lymphoma (LPL) and its clinical significance. METHODS: The clinical data of 32 patients with initial LPL (LPL group) and physical examination data of 25 healthy persons (control group) who underwent physical examination in our hospital during the same period were collected. The differences of platelet (Plt), D-Dimer (D-D), fibrinogen (Fib), thrombin time (TT), prothrombin time (PT) and activated partial thrombin time (APTT) between the two groups were compared. RESULTS: The Plt count in LPL group [ (137.06±40.14)×109/L] was significantly lower than that in control group [ (215.07±33.25)×109/L], D-D [ (1.01±0.16) mg/L, PT [ (13.01±1.37) s] and APTT [ (40.96±7.24) s] in LPL group were significantly higher than those in control group [ (0.37±0.09) mg/L, (11.96±0.87) s, (25.07±5.13) s] (P＜0.01); there was no significant difference in TT and Fib levels between the two groups (P＞0.05). There was no significant difference in Plt, D-D, Fib, AP, TT and APTT among LPL patients secreting different types of immunoglobulin (Ig) (P＞0.05). After treatment, the coagulation function of LPL patients returned to normal, and no death cases occurred due to hemorrhage or thrombosis. CONCLUSION: LPL patients have hypercoagulable state blood and abnormal coagulation function, but which not closely relates to with the type of Ig secreted by patients.

[Expression Level and Target Gene Prediction of miR-181b in Patients with Chronic Lymphocytic Leukemia].

OBJECTIVE: To analyze the diagnostic value of multiple reverse transcription-polymerase chain reaction (RT-PCR) for detecting different fusion genes in children with primary acute lymphoblastic leukemia (ALL). METHODS: The clinical data of 80 children with ALL treated in the 2nd affiliated hospital of Xi'an Medical College from September 2012 to September 2017 were collected and retrospectively analyzed. Immunophenotype, chromosome karyotype and fusion gene were analyzed. RESULTS: Immunophenotyping showed that there were 2 cases of mixed expression of myeloid + B system, 2 cases with pre- B expression, 58 cases with former B expression, 11 cases with CD13 combined with pre- B expression, 4 cases with CD5 combined with pre- B expression, and 3 cases with CD2 combined with pre- B expression. The results of chromosome karyotype analysis showed that among 72 cases of karyotype analysts 5 cases could not be analyzed, 27 cases were determined to be normal karyotype, 11 cases with abnormal karyotype and 29 cases without mitotic phase. Six fusion genes were expressed in 30 cases (37.50%) of 80 ALL children, including MLL/AF9, CBF/MYH 11, BCR/ABL, TLS/ERG, MLL/ENL and TEL/AML1. Among the 3 cases with MLL/AF9 fusion gene expression [t(9;11)], 2 cases showed a poor response to early treatment, but achieved complete remission after intensive chemotherapy, and 1 case accepted bone marrow transplantation; in 1 case with CBF/MYH 11 fusion gene expression, treatment was abandoned by family members, and 4 cases with BCR/ABL fusion gene expression [t (9;22) (q34; q11)] were all showed poor response to early treatment, and achieved complete remission after intensive chemotherapy. All the fusion genes were positive during remission, including 2 cases of bone marrow transplantation; 1 case with TLS/ERG fusion gene expression [t (16;21)] displayed poor response to early treatment, and completely remitted after intensive chemotherapy; 2 cases with MLL/ENL fusion gene expression [t (11;19)] recurred during chemotherapy; 19 cases with TEL/AML1 fusion gene expression [t (12;21)] also achieved complete remission. 4 cases achieved a partial remission. CONCLUSION: Genotyping can make up for the insufficiency of MICM typing, and multiplex RT-PCR can be used to rapidly detect the fusion genes caused by chromosomal aberration in children with ALL.

Metabolic remodeling by TIGAR overexpression is a therapeutic target in esophageal squamous-cell carcinoma.

Rationale: Whole-genome sequencing has identified many amplified genes in esophageal squamous-cell carcinoma (ESCC). This study investigated the role and clinical relevance of these genes in ESCC. Methods: We collected ESCC and non-tumor esophageal tissues from 225 individuals who underwent surgery. Clinical data were collected and survival time was measured from the date of diagnosis to the date of last follow-up or death. Patient survival was compared with immunohistochemical staining score using Kaplan-Meier methods and hazard ratios were calculated by Cox models. Cells with gene overexpression and knockout were analyzed in proliferation, migration and invasion assays. Cells were also analyzed for levels of intracellular lactate, NADPH, ATP and mRNA and protein expression patterns. Protein levels in cell line and tissue samples were measured by immunoblotting or immunohistochemistry. ESCC cell were grown as xenograft tumors in nude mice. Primary ESCC in genetically engineered mice and patient-derived xenograft mouse models were established for test of therapeutic effects. Results: We show that TP53-induced glycolysis and apoptosis regulator (TIGAR) is a major player in ESCC progression and chemoresistance. TIGAR reprograms glucose metabolism from glycolysis to the glutamine pathway through AMP-activated kinase, and its overexpression is correlated with poor disease outcomes. Tigar knockout mice have reduced ESCC tumor burden and growth rates. Treatment of TIGAR-overexpressing ESCC cell xenografts and patient-derived tumor xenografts in mice with combination of glutaminase inhibitor and chemotherapeutic agents achieves significant more efficacy than chemotherapy alone. Conclusion: These findings shed light on an important role of TIGAR in ESCC and might provide evidence for targeted treatment of TIGAR-overexpressing ESCC.

miR-146a and miR-152 in prostate cancer and clinicopathological parameters.

PURPOSE: To investigate the expression of miR-146a and miR-152 in the serum of patients with prostate cancer and the relationship between their expression and clinicopathologic parameters. METHODS: 56 patients with prostate cancer and 56 healthy volunteers were included in this study and the relationship between the expression levels of miR-146a and miR-152 and the clinicopathological parameters of the patients with prostate cancer were analyzed. ROC curve was used to search the diagnostic value of each indicator. RESULTS: The expression of miR-146a in patients in the cancer group was significantly higher than that in the normal group (p<0.05). The expression of miR-152 in the cancer group was significantly lower than that in the normal group (p<0.05). The expression level of miR-146a in the patients with prostate cancer was closely related to clinical staging, the presence or absence of bone metastasis, tPSA and pathological staging (p<0.001) and the expression level of miR-152 in the patients with prostate cancer was closely related to clinical staging, the presence or absence of bone metastasis and pathological staging (p<0.001). CONCLUSION: The expression level of miR-146a showed a trend of up-regulation in prostate cancer, and the expression level of miR-152 had a trend of down-regulation in prostate cancer, and the results of partial correlation analysis showed that the expression level of miR-146a and miR-152 was negatively correlated with each other in the serum of the patients with prostate cancer.

The value of FGF9 as a novel biomarker in the diagnosis of prostate cancer.

Background: Fibroblast growth factor 9 (FGF9) is reported to be associated with the pathogenesis of cancers. However, its clinic significance in prostate cancer (PCa) had not yet to be elucidated. The aim of this study was to investigate the diagnostic value of FGF9 in PCa. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were used to detect the expression of serum FGF9 at mRNA and protein level in 90 PCa patients, 48 prostatic benign diseases (PBD) patients and 30 normal individuals. The association between FGF9 and clinicopathological features was determined by Chi-square test. Receiver-operator characteristic (ROC) was established to evaluate the diagnostic performance of FGF9 and PSA. Results: Serum FGF9 expression was significantly elevated in PCa patients (p < .001) and was obviously decreased after surgery (p < .001). FGF9 expression was also associated with lymph node metastasis (p = .010). The diagnostic value of FGF9 was higher than the conventional tumor marker PSA with a AUC of 0.846 combined with a sensitivity of 83.3% and a specificity of 81.1%. Conclusions: Serum FGF9 may be employed as a potential diagnostic biomarker of PCa.

[Expression of sB7-H4 in Serum and Lymphoma Tissues of Patients with Malignant Lymphoma and Its Value for Diagnosis and Re-Examine of Lymphoma].

OBJECTIVE: To study the soluble B7-H4 (sB7-H4) expression in serum and lymphoma tissues of patients with malignant lymphoma (ML) and its value for diagnosis and re-examination lymphoma. METHODS: The serum samples from 83 cases of ML were collected, among them 69 cases of newly diagnosed ML were enrolled in group A including 11 cases of Hodgkin's lymphoma (NHL group) and 58 cases of non-Hodgkin's lymphoma (NHL group), the serum samples from 14 cases of relapsed ML were enrolled in group B; at the same time the serum samples of 50 healthy persons conformed by physical examination were collected and enrolled in control group. The double antibody sandwich ELISA was used to detect the serum level of sB7-H4 in each group, and immunohistochemistry method was used to detect the expression of sB7-H4 in malignant lymphoma and reactive lymphoid hyperplasia tissues. RESULTS: The serum level of sB7-H4 in the group A was significantly increased in comparison with the group B and control group, and the level of group B was significantly higher than that in the control group (P<0.05); the serum level of sB7-H4 in the NHL group was significantly increased in comparison with HL group and control group, and the level of HL group was higher than that of control group (P<0.05). The expression of sB7-H4 in reactive lymphoid hyperplasia tissues was negative, but the positive expression rate in malignant lymphoma tissues was 47.50%, suggesting the positive rate of sB7-H4 in malignant lymphoma tissues was significantly higher than that of reactive lymphoid hyperplasia tissues (P<0.05). CONCLUSION: The high expression of sB7-H4 in serum and lymphoma tissues of patients with malignant lymphoma has a certain value for the diagnosis and re-examination of patients with malignant lymphoma.

CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population.

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.