Platelet-lymphocyte ratio predicts chemotherapy response and prognosis in patients with gastric cancer undergoing radical resection.

Background: Amounting literatures have reported the significance of systemic inflammatory markers for evaluating tumor prognosis. But few studies have systematically compared their superiority and their impact on adjuvant chemotherapy. Aims: We aimed to investigate the ability of inflammatory markers to predict the efficacy of chemotherapy in GC patients undergoing radical therapy and to identify an effective methodology based on the study's findings that would enable clinicians to differentiate between chemotherapy-responsive populations. Methods: We retrospectively enrolled 730 GC patients who underwent radical gastrectomy. Fibrinogen (FIB), platelet-lymphocyte ratio (PLR), systemic inflammation response index (SIRI), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR) and lymph node ratio (LNR) were grouped according to cutoff values. Their clinical significance for GC prognosis was determined by multivariate COX regression analysis in the 730 GC patients and high/low PLR status subgroups. Cases were divided into four groups according to PLR status and adjuvant chemotherapy status and survival was compared among groups. Results: Multivariate analysis showed that PLR was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) of GC patients. Adjuvant chemotherapy improved survival more significantly in patients with low PLR than that with high PLR. Among patients receiving adjuvant chemotherapy, low PLR was significantly associated with prolonged survival in TNM stage II, but not in TNM stage III. Conclusion: Preoperative high PLR is an independent risk factor for GC patients undergoing radical gastrectomy and adversely affects the postoperative chemotherapy effect.

Glucose metabolism-based signature predicts prognosis and immunotherapy strategies for colon adenocarcinoma.

BACKGROUND: The global prevalence and metastasis rates of colon adenocarcinoma (COAD) are high, and therapeutic success is limited. Although previous research has primarily explored changes in gene phenotypes, the incidence rate of COAD remains unchanged. Metabolic reprogramming is a crucial aspect of cancer research and therapy. The present study aims to develop cluster and polygenic risk prediction models for COAD based on glucose metabolism pathways to assess the survival status of patients and potentially identify novel immunotherapy strategies and related therapeutic targets. METHODS: COAD-specific data (including clinicopathological information and gene expression profiles) were sourced from The Cancer Genome Atlas (TCGA) and two Gene Expression Omnibus (GEO) datasets (GSE33113 and GSE39582). Gene sets related to glucose metabolism were obtained from the MSigDB database. The Gene Set Variation Analysis (GSVA) method was utilized to calculate pathway scores for glucose metabolism. The hclust function in R, part of the Pheatmap package, was used to establish a clustering system. The mutation characteristics of identified clusters were assessed via MOVICS software, and differentially expressed genes (DEGs) were filtered using limma software. Signature analysis was performed using the least absolute shrinkage and selection operator (LASSO) method. Survival curves, survival receiver operating characteristic (ROC) curves and multivariate Cox regression were analyzed to assess the efficacy and accuracy of the signature for prognostic prediction. The pRRophetic program was employed to predict drug sensitivity, with data sourced from the Genomics of Drug Sensitivity in Cancer (GDSC) database. RESULTS: Four COAD subgroups (i.e., C1, C2, C3 and C4) were identified based on glucose metabolism, with the C4 group having higher survival rates. These four clusters were bifurcated into a new Clust2 system (C1 + C2 + C3 and C4). In total, 2175 DEGs were obtained (C1 + C2 + C3 vs. C4), from which 139 prognosis-related genes were identified. ROC curves predicting 1-, 3- and 5-year survival based on a signature containing nine genes showed an area under the curve greater than 0.7. Meanwhile, the study also found this feature to be an important predictor of prognosis in COAD and accordingly assessed the risk score, with higher risk scores being associated with a worse prognosis. The high-risk and low-risk groups responded differently to immunotherapy and chemotherapeutic agents, and there were differences in functional enrichment pathways. CONCLUSIONS: This unique signature based on glucose metabolism may potentially provide a basis for predicting patient prognosis, biological characteristics and more effective immunotherapy strategies for COAD.

Prediction and therapeutic targeting of the tumor microenvironment-associated gene CTSK in gastric cancer.

BACKGROUND: Cathepsin-K (CTSK) is overexpressed in Gastric cancer (GC) and the mechanism of its overexpression in GC is still unclear. The present work found CTSK as a potential predictive biomarker and immunotherapeutic target for GC based on the tumor microenvironment (TME). METHODS: From public databases, gene expression profiles and clinical data of GC were downloaded to analyze the distribution of stromal and immune cells and tumor abundance in TME. Differentially expressed genes (DEGs) associated with TME were obtained by differential analysis, followed by cross-screening to obtain CTSK as a gene associated with TME. Next, a series of methods and tools were employed to explore the relationships between clinicopathological features of GC and CTSK expression as well as prognosis, tumor immune microenvironment, immune checkpoints and drug sensitivity. And GSEA was used to investigate the potential role of CTSK in the tumor microenvironment of GC. RESULTS: From the dataset, we obtained a total of 656 DEGs associated with TME and the stromal component of TME was found to be closely involved in GC prognosis. CTSK was cross-screened as the key gene associated with TME by the PPI network and univariate Cox regression analysis. Pan-cancer analysis revealed significant high expression of CTSK in a variety of cancers. Subsequently, we hypothesized that high-expressed CTSK was closely correlated with poor prognosis and lymph node metastasis of tumors, and that CTSK, a GC TME-related gene, was largely involved in a range of biological behaviors of tumors, with a significant correlation between several immune cells. CONCLUSION: CTSK was validated as a potential prognostic biomarker related to TME of GC and could be a promising next-generation immunotherapeutic target for GC.

Prognostic utility of TME-associated genes in pancreatic cancer.

Background: Pancreatic cancer (PC) is a deadly disease. The tumor microenvironment (TME) participates in PC oncogenesis. This study focuses on the assessment of the prognostic and treatment utility of TME-associated genes in PC. Methods: After obtaining the differentially expressed TME-related genes, univariate and multivariate Cox analyses and least absolute shrinkage and selection operator (LASSO) were performed to identify genes related to prognosis, and a risk model was established to evaluate risk scores, based on The Cancer Genome Atlas (TCGA) data set, and it was validated by external data sets from the Gene Expression Omnibus (GEO) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Multiomics analyses were adopted to explore the potential mechanisms, discover novel treatment targets, and assess the sensitivities of immunotherapy and chemotherapy. Results: Five TME-associated genes, namely, FERMT1, CARD9, IL20RB, MET, and MMP3, were identified and a risk score formula constructed. Next, their mRNA expressions were verified in cancer and normal pancreatic cells. Multiple algorithms confirmed that the risk model displayed a reliable ability of prognosis prediction and was an independent prognostic factor, indicating that high-risk patients had poor outcomes. Immunocyte infiltration, gene set enrichment analysis (GSEA), and single-cell analysis all showed a strong relationship between immune mechanism and low-risk samples. The risk score could predict the sensitivity of immunotherapy and some chemotherapy regimens, which included oxaliplatin and irinotecan. Various latent treatment targets (LAG3, TIGIT, and ARID1A) were addressed by mutation landscape based on the risk model. Conclusion: The risk model based on TME-related genes can reflect the prognosis of PC patients and functions as a novel set of biomarkers for PC therapy.

Does the LHPP gene share a common biological function in pancancer progression?

Although emerging evidence has revealed that LHPP, a histidine phosphatase protein, suppresses the progression of different cancers, a pan-cancer analysis still remains unavailable. Therefore, we first utilized different bioinformatics tools to explore the tumor inhibitory role of LHPP protein across 33 tumor types based on the TCGA project. Additionally, HGC-27 gastric cancer cells were used to evaluate the biological functions of LHPP after stable transfection with lentiviruses. Consequently, LHPP mRNA and protein expression were down-regulated in the most cancer tissues corresponding to normal tissues. The data showed that patients with higher LHPP performance had a better prognosis of overall survival (OS) and disease-free survival (DFS) in brain glioma and renal carcinoma. In addition, we found that enhancement of LHPP expression attenuated the proliferation, migration and invasion of gastric cancer cells. The expression levels of cell-cycle-related and EMT-related molecules, such as CDK4, CyclinD1, Vimentin and Snail, were clearly reduced. Moreover, a genetic alteration analysis showed that the most frequent mutation types in LHPP protein was amplification. The patients without LHPP mutation showed a better tendency of prognosis in UCEC, STAD and COAD. Cancer-associated fibroblast infiltration was also observed in head and neck squamous cell carcinoma, stomach adenocarcinoma and testicular germ cell tumors. In summary, our pancancer analysis among various tumor types could provide a comprehensive understanding of LHPP biological function in the progression of malignant diseases and promote the development of novel therapeutic targets.

Cuproptosis-Related genes in the prognosis of colorectal cancer and their correlation with the tumor microenvironment.

Colorectal cancer (CRC) is a common tumor disease of the digestive system with high incidence and mortality. Cuproptosis has recently been found to be a new form of cell death. The clinical significance of cuproptosis-related genes (CRGs) in CRC is not clear. In this study, The Cancer Genome Atlas Colon and Rectal Cancer dataset was used to analyze the relationship between CRGs and clinical characteristics of CRC by differential expression analysis and Kaplan-Meier survival (K-M) analysis. Based on CRGs, prognosis model and risk score of CRC was constructed in COADREAD by multivariate Cox analysis. Receiver operating curves (ROC) analysis, K-M analysis and calibration analysis in GDC TCGA Colon Cancer dataset were applied to validating model. Subsequently, the relationship between risk score of CRC and immune microenvironment was analyzed by multiple immune score algorithms. Finally, we found that most CRGs were differentially expressed between tumors and normal tissues. Some CRGs were differentially expressed among different clinical characteristics. K-M analysis showed that the CRGs were related to overall survival (OS), disease-specific survival, and progression-free survival. Subsequently, DLAT and CDKN2A were identified as risk factors for OS in CRC by multivariate Cox analysis, and the risk score was established. K-M analysis showed that there was a significant difference in OS between the high-risk and low-risk groups, which were grouped by risk score median. ROC analysis showed that the risk score performs well in predicting the 1-year, 3-year and 5-year OS. Enrichment analysis showed that the differentially expressed genes between the high- and low-risk groups were enriched in immune-related signaling pathways. Further analysis showed that there were significant differences in the levels of immune cells and stromal cells between the high- and low-risk groups. The high-risk group had higher levels of immune cells and interstitial cells. At the same time, the high-risk group had a higher immune escape ability, and the predicted immune treatment response in the high-risk group was poor. In conclusion, CRGs can be used as prognostic factors in CRC and are closely related to the levels of immune cells and stromal cells in the tumor microenvironment.

The nuclear-localized GHR is involved in the cell proliferation of gastric cancer, and pegvisomant may be an important potential drug to inhibit the proliferation of gastric cancer cells.

Under normal physiological conditions, growth hormones (GH) play an important role in body growth and metabolism. A recent study showed that GH has important biological effects on gastric cancer (GC) both in vitro and in vivo. However, the biological properties of GH/GHR (GHR, growth hormone receptor) in GC cells have not been fully elucidated. To this end, we systemically studied the biological properties of GH in GC cells and found that GH/GHR was transported into the nuclei of GC cells. Furthermore, we investigated the functions of nuclear GHR and its potential mechanisms of action. We found that nuclear-localized GHR was closely related to the proliferation of GC cells. In addition, we systematically studied the effect of a GHR inhibitor (pegvisomant) on GC in vivo and in vitro, and the results showed that pegvisomant can not only inhibit the proliferation of GC cells but also inhibit the nuclear localization of GHR, suggesting that pegvisomant may be a dual-effect antagonist. Current research indicates that GHR may be a potential target for the treatment of GC.

LHPP suppresses colorectal cancer cell migration and invasion in vitro and in vivo by inhibiting Smad3 phosphorylation in the TGF-ß pathway.

The roles of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) in tumorigenesis have been recently proven in hepatocellular carcinoma (HCC), cervical, pancreatic, bladder, and thyroid cancers. Previous research demonstrated that LHPP repressed cell proliferation and growth by inactivating the phosphatidylinositol 3-kinase/AKT signaling pathway in vitro and in vivo. However, the functions and potential mechanisms of LHPP as a tumor suppressor in colorectal cancer (CRC) metastasis are still unknown. Consequently, the Transwell assay and xenograft nude model showed that LHPP inhibited migration and invasion of CRC cells in vitro and in vivo, respectively. The expression of total and nuclear epithelial-to-mesenchymal transition (EMT)-related proteins were significantly reduced after LHPP upregulation. Human Gene Expression Array and IPA (Ingenuity Pathway Analysis) commercial software were applied to identify differentially expressed genes (DEGs) and potential cell signaling pathways. A total of 330 different genes were observed, including 177 upregulated genes and 153 downregulated genes. Bioinformatics analysis suggested that the transforming growth factor-ß (TGF-ß) signaling pathway was highly inactivated in this study. Then, Smad3 phosphorylation was apparently decreased, whereas Smad7 expression was markedly enhanced after upregulating LHPP expression. These results were proven once again after TGF-ß1 stimulation. Furthermore, a specific inhibitor of Smad3 phosphorylation (SIS3) was applied to verify that LHPP repressed EMT of cancer cells by attenuating TGF-ß/Smad signaling. The results suggested that suppression of the TGF-ß/Smad signaling pathway by LHPP overexpression could be abolished by SIS3.

Identification of core genes and clinical outcomes in tumors originated from endoderm (gastric cancer and lung carcinoma) via bioinformatics analysis.

ABSTRACT: During last decade, bioinformatics analysis has provided an effective way to study the relationship between various genes and biological processes. In this study, we aimed to identify potential core candidate genes and underlying mechanisms of progression of lung and gastric carcinomas which both originated from endoderm. The expression profiles, GSE54129 (gastric carcinoma) and GSE27262 (lung carcinoma), were collected from GEO database. One hundred eleven patients with gastric carcinoma and 21 health people were included in this research. Meanwhile, there were 25 lung carcinoma patients. Then, 75 differentially expressed genes were selected via GEO2R online tool and Venn software, including 31 up-regulated genes and 44 down-regulated genes. Next, we used Database for Annotation, Visualization, and Integrated Discovery and Metascpe software to analyze Kyoto Encyclopedia of Gene and Genome pathway and gene ontology. Furthermore, Cytoscape software and MCODE App were performed to construct complex of these differentially expressed genes . Twenty core genes were identified, which mainly enriched in extracellular matrix-receptor interaction, focal adhesion, and PI3K-Akt pathway (P < .01). Finally, the significant difference of gene expression between cancer tissues and normal tissues in both lung and gastric carcinomas was examined by Gene Expression Profiling Interactive Analysis database. Twelve candidate genes with positive statistical significance (P < .01), COMP CTHRC1 COL1A1 SPP1 COL11A1 COL10A1 CXCL13 CLDN3 CLDN1 matrix metalloproteinases 7 ADAM12 PLAU, were picked out to further analysis. The Kaplan-Meier plotter website was applied to examine relationship among these genes and clinical outcomes. We found 4 genes (ADAM12, SPP1, COL1A1, COL11A1) were significantly associated with poor prognosis in both lung and gastric carcinoma patients (P  < .05). In conclusion, these candidate genes may be potential therapeutic targets for cancer treatment.

Tumor suppressor LHPP regulates the proliferation of colorectal cancer cells via the PI3K/AKT pathway.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer­related mortality worldwide. Thus, identification of the mechanisms involved in the progression of CRC has become a crucial element of facilitating early CRC diagnosis and targeted therapy for patients with advanced CRC. Currently, Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a type of histidine phosphatase protein, has been confirmed as a tumor suppressor in hepatocellular carcinoma (HCC) and cervical cancer. However, the functions and molecular mechanisms underlying LHPP in CRC remain undefined. The present study revealed that dysregulation of LHPP was frequently observed in CRC tissues and was positively correlated with tumor severity and poor prognosis. Functional experiments demonstrated that overexpression of LHPP impeded CRC cell growth and proliferation in vitro, and was associated with a change in p53 expression and PI3K/AKT activity. In contrast, silencing of LHPP significantly promoted cell growth and proliferation by modulating the PI3K/AKT signaling pathway. Notably, the anti­CRC effects of LHPP were also observed in nude mouse in vivo experiments. Overall, the data obtained in the present study suggested that LHPP may be exploited as a diagnostic and prognostic candidate for patients with CRC.

Efficiency of CAR-T Therapy for Treatment of Solid Tumor in Clinical Trials: A Meta-Analysis.

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy has achieved unprecedented success among hematologic tumors, but its role in treating solid tumors is still unclear. METHODS: A comprehensive search of electronic databases up to June 1, 2018, was carried out by two independent reviewers. We included studies which focused on the association between CAR-T cell therapy and patient response rate and survival time in solid tumors. RESULTS: 22 studies with 262 patients were included in our meta-analysis. The overall pooled response rate of CAR-T cell therapy was 9% (95% confidence interval (CI): 4-16%). Subgroup analysis (analyses) demonstrated that CAR-T therapy could perform its best therapeutic effect on neuroblastoma, while barely works among gastrointestinal malignancies. Moreover, the treatment efficacy was not significantly impacted by different treatment strategies (lymphodepletion before T cell infusion, transfection method, cell culture duration, persistence of CAR-T cells, transfection efficacy, total cell dose, and administration of IL-2). Only T cell culture duration was associated with better clinical prognosis. CONCLUSIONS: Although CAR-T cell therapy did not have satisfactory responses in solid tumors, researchers were still holding an optimistic attitude towards its future efficacy with more modifications of its structure.

Prognostic Role of Pretreatment Plasma D-Dimer in Patients with Solid Tumors: a Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Elevated pretreatment plasma D-dimer level has been reported as an unfavorable prognostic indicator in several malignancies. The aim of this meta-analysis was to evaluate the prognostic value of elevated D-dimer level in solid tumors. METHODS: A comprehensive search of electronic databases up to June 10, 2017 was carried out by two independent reviewers. We included studies exploring the association between pretreatment plasma D-dimer level and patients' survival outcomes in solid tumors. Overall survival (OS) was regarded as primary outcome and progression-free survival (PFS), disease-free survival (DFS) as well as cancer-specific survival (CSS) were chosen as secondary outcomes. Hazard ratio and 95% confidence interval (CI) were extracted directly or indirectly from included studies. RESULTS: 49 studies with 13001 patients were included in our meta-analysis. Elevated D-dimer was markedly associated with poor OS (pooled HR = 1.90, 95% CI = 1.63 - 2.20, P < 0.001). The effect was observed in all different tumor sites, disease stages, cut-off values and ethnicities. Meanwhile, patients with a high plasma D-dimer had a shorter PFS (HR = 1.46, 95% CI = 1.22-1.76; P < 0.001), DFS (HR = 2.02, 95% CI = 1.56-2.62) and CSS (HR = 2.04, 95% CI= 1.58 - 2.64). CONCLUSIONS: Analysis of the pretreatment plasma D-dimer might provide useful information to predict prognosis in patients with solid tumors.

Hypermethylation of miRNA-589 promoter leads to upregulation of HDAC5 which promotes malignancy in non-small cell lung cancer.

Histone deacetylases (HDACs) are crucial for regulating chromatin activity, which plays a critical role in cell proliferation, differentiation, and apoptosis of various cancers. Therefore, HDAC inhibitors have been applied as effective therapeutic agents for cancer treatment. However, the expression profiles and regulatory mechanisms of histone deacetylases in lung cancer are not well understood. In the present study, aberrant high levels of HDAC5 were observed in non-small cell lung cancer (NSCLC) and further analysis indicated a negative relationship between HDAC5 and a tumor suppressor, miR­589­5p, in NSCLC specimens. Consistently, miR­589­5p reduced the expression of HDAC5 by targeting the 3'UTR of HDAC5 mRNA in NSCLC cells. Considering the loss of miR­589­5p in NSCLC, the methylation status of the miR-589 gene promoter was examined. The hypermethylation of the miR-589 gene promoter was more significant in NSCLC cells compared with lung epithelial cells, and methylation inhibition by 5-aza-2-deoxycytidine (5-Aza-dC) decreased HDAC5 expression. Furthermore, several downstream gene clusters of HDAC5 were studied in the present investigation. As a result, miR­589­5p/HDAC5 pathway was found to regulate a number of cell cycle and epithelial-mesenchymal transition (EMT)-related genes in NSCLC cells. In vitro and in vivo phenotype experiments revealed a critical role of miR­589­5p/HDAC5 pathway in the migration, invasion, and tumorigenicity of NSCLC cells. These findings demonstrate a novel mechanism for deregulation of HDAC5 in NSCLC and suggest that miR­589­5p/HDAC5 pathway may represent a new prognostic biomarker and therapeutic target against NSCLC.

Decreased Expression of Hsa_circ_00001649 in Gastric Cancer and Its Clinical Significance.

Background. It has been reported that circRNAs are differentially expressed in a wide range of cancers and could be used as a new biomarker for diagnosis. However, the correlation between circRNAs and gastric cancer (GC) it is still unclear. Materials and Methods. In this study, by using real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs), we detected the expression level of hsa_circ_0001649 in tissue and serum samples from GC patients. Results. We found that hsa_circ_0001649 expression was significantly downregulated in GC tissue compared with their paired paracancerous histological normal tissues (PCHNTs) (P < 0.01). We next analyzed the expression level of hsa_circ_0001649 in serum samples between preoperative and postoperative GC patients. We found that its level in serum was significantly upregulated after surgery (P < 0.01). The area under the receiver operating characteristic (ROC) curve was 0.834. Moreover, the expression level of hsa_circ_0001649 was significantly correlated with pathological differentiation (P = 0.039). Conclusion. Our test suggested that hsa_circ_0001649 was significantly downregulated in GC and may become a novel potential biomarker in the diagnosis of GC.

Detection of OSR2, VAV3, and PPFIA3 Methylation in the Serum of Patients with Gastric Cancer.

AIM: This study was to evaluate the diagnostic value of OSR2, VAV3, and PPFIA3 hypermethylation in gastric cancer (GC) patients. PATIENTS AND METHODS: By using methylation-specific polymerase chain reaction (MSP), we detected the methylation status in tissue and serum samples from 48 gastric cancer (GC) patients and 25 normal individuals. RESULTS: We found that OSR2, VAV3, and PPFIA3 were methylated in 70.8% (34/48), 54.2% (26/48), and 60.4% (29/48) of GC tissue, respectively. On the contrary, those genes were barely methylated in their paired paracancerous histological normal tissues (PCHNTs) (all P values < 0.01). We next analyzed the methylated OSR2, VAV3, and PPFIA3 in serum DNA. Compared with 25 normal individuals, those three genes were significantly hypermethylated in GC patients serum samples (all P values < 0.01). Regarding their diagnostic value in serum samples, the combined sensitivity of at least one positive among the three markers in serum was 83.3%, with a specificity of 88%. CONCLUSION: Our test suggested that methylation of OSR2, VAV3, and PPFIA3 genes in serum sample may offer a good alternative in a simple, promising, and noninvasive detection of GC.

Cyclophosphamide, epirubicin and fluorouracil chemotherapy-induced alteration of haemostasis markers in breast cancer patients.

The occurrence of chemotherapy-induced alterations in markers of haemostasis during chemotherapy has been reported previously. However, the change of the haemostasis markers in the cyclophosphamide, epirubicin and fluorouracil (CEF) regimen remains unclear. The aim of the present study was to identify the change of the haemostasis markers during systemic chemotherapy (600 mg/m2 cyclophosphamide, 80 mg/m2 epirubicin and 500 mg/m2 fluorouracil; four courses over 21 days) to investigate its influence on the haemostasis markers of breast cancer patients and to discuss the requirement of anticoagulation therapy. D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB) values were obtained before chemotherapy and on days 1, 4, 7 and 21. The results show that PT, D-dimer and FIB were not prolonged prior to chemotherapy compared to that under the control. APTT was prolonged until day 4. The levels of D-dimer and APTT were significantly higher compared to those of the breast cancer patients before receiving chemotherapy and controls on days 1, 4, 7 and 21 after chemotherapy. Alteration of the haemostasis markers occurred in the breast cancer patients under the CEF chemotherapy regimen. As there is an increased risk of deep vein thrombosis and pool prognosis of cancer patients, anticoagulant therapy should be considered.

FGFR2 gene polymorphisms are associated with breast cancer risk in the Han Chinese population.

AIMS AND BACKGROUND: Breast cancer is one of the most common neoplasms among women in many developing countries including China, and is the leading cause of female cancer-related deaths worldwide. METHODS: In the current study, we analyzed the relationship between 14 tag single-nucleotide polymorphisms (tSNPs) and breast cancer risk in the Han Chinese population including 185 breast cancer patients and 199 healthy women controls on the different types of breast cancer and menopausal status. RESULTS: Overall, we found rs2981579 in the FGFR2 gene, and rs2380205 were associated with breast cancer susceptibility. CONCLUSIONS: These findings indicate that FGFR2 was associated with breast cancer risk in the Han Chinese population, support the hypothesis that the applicability of a common susceptibility locus must be confirmed among genetically different populations.

miR-338-3p suppresses gastric cancer progression through a PTEN-AKT axis by targeting P-REX2a.

UNLABELLED: Results from recent studies suggest that aberrant microRNA expression is common in numerous cancers. Although miR-338-3p has been implicated in hepatocellular carcinoma, its role in gastric cancer is unknown. To this end, we report that miR-338-3p is downregulated in both gastric cancer tissue and cell lines. Forced expression of miR-338-3p inhibited cell proliferation and clonogenicity and induced a G1-S arrest as well as apoptosis in gastric cancer cells. Furthermore, P-Rex2a (PREX2) was identified as a direct target of miR-338-3p, and silencing P-Rex2a resulted in the same biologic effects of miR-338-3p expression in gastric cancer cells. Furthermore, both enforced expression of miR-338-3p or silencing of P-Rex2a resulted in activation of PTEN, leading to a decline in AKT phosphorylation. Also, miR-338-3p markedly inhibited the in vivo tumorigenicity in a nude mouse xenograft model system. These results demonstrate that miR-338-3p affects gastric cancer progression through PTEN-AKT signaling by targeting P-Rex2a in gastric cancer cells, which posits miR-338-3p as a novel strategy for gastric cancer treatment. IMPLICATIONS: miR-338-3p acts as a novel tumor suppressor that blocks the growth of gastric cancer cells through PTEN-PI3K signaling by targeting P-Rex2a.

Dysregulation of miRNAs and their potential as biomarkers for the diagnosis of gastric cancer.

Recent studies demonstrated that microRNA (miRNA) expression is dysregulated in numerous human cancers. In this study, we investigated the expression patterns of 8 miRNAs in gastric cancer and evaluated their clinical significance in order to identify potential biomarkers for gastric cancer diagnosis. Total RNA was extracted from gastric cancer and normal tissues from 20 pairs of paraffin-embedded specimens. The expression levels of the miRNAs were detected by quantitative reverse transcriptase polymerase chain reaction using specific stem-loop primers, with U6 as the internal reference gene. The association between miRNA expression level and clinicopathological factors was investigated. The expression of miR-21, -103, -106a, -221 and -222 in gastric cancer samples was significantly higher compared to that in the paired normal samples. Conversely, the expression of miR-143 and -195 in cancer tissues was significantly lower compared to that in normal tissues. However, miR-126 exhibited no difference between gastric cancer and normal tissues. A multivariate analysis demonstrated that the expression of miR-143 and -195 were associated with clinicopathological parameters, including depth of invasion and lymph node metastasis. This association may be applicable to future decisions regarding treatment or as a diagnostic biomarker.

Prevention of anastomotic leakage after low anterior resection in rectal cancers.

BACKGROUND/AIMS: To review the available data on the efficacy of the measures that are directed towards prevention of anastomotic leakage after low anterior resection and introduce a promising method based on our own experience. METHODOLOGY: The Medline database was searched for studies on the prevention of anastomotic leak after low anterior resection in rectal cancers. RESULTS: Two meta-analyses of the results indicate that a routine defunctioning stoma reduces the rate of clinically relevant anastomotic leakages and is thus recommended in such patients. However, the morbidity of the stoma itself, as well as the morbidity and mortality of its closure should also be considered and pending further trials to clarify its role. Studies suggested that omentoplasty may reduce the leakage rate, but there is a paucity of large randomized trials. A non-randomized trial together with our clinical experience indicated Valtrac-secured intracolonic bypass (VIB) may be a promising method in prevention of anastomotic leakage in rectal cancers. CONCLUSIONS: VIB appears so far to be a promising method for the prevention of anastomotic leak after low anterior resection in rectal cancers. However, further randomized controlled studies are still required to determine its clinical efficacy.