The objective of this study was to evaluate the role of HOTAIR long noncoding RNA in gastric cancer metastasis. We analyzed HOTAIR expression levels by real-time reverse transcription PCR and ...Northern blot analysis in 100 gastric tissues (50 gastric cancer tissues and 50 adjacent normal mucosa), and in four gastric cancer cell lines. Transient RNAi-mediated knockdown and pcDNA-mediated overexpression of HOTAIR were performed. Stable shRNA-mediated knockdown and lentiviral-mediated overexpression of HOTAIR were to study the role of HOTAIR on in vivo tumorigenicity and metastatic burden in the context of xenograft assays. Proteomic profiling was performed to decipher differential protein expression in cells with different HOTAIR expression levels. One of the differentially regulated proteins, Poly r(C)-binding protein (PCBP) 1, was subsequently validated and its function evaluated through xenograft assays. Expression of HOTAIR was significantly higher in cancerous tissues than in adjacent normal mucosa. HOTAIR expression levels dictated in vitro and in vivo tumorigenicity and metastatic potential in these cells. PCBP1 and HOTAIR have an inverse relationship, both at expression level and in function. A direct interaction between the two was confirmed through RNA immunoprecipitation coupled with quantitative real-time PCR. PCBP1 was confirmed to be an inhibitor of gastric cancer pathogenesis and as functionally opposite to HOTAIR long noncoding RNA. In conclusion, HOTAIR expression may serve as a potentially important disease biomarker for the identification of high-risk gastric cancer patients. Moreover, our findings provide mechanistic evidence for HOTAIR overexpression and PCBP1 downregulation and the ensuing malignant phenotype in both cultured and xenograft gastric cancer cells.
Colorectal cancer (CRC) incidence has increased among patients aged <50 years. Exploring high-risk factors and screening high-risk populations may help lower early-onset CRC (EO-CRC) incidence. We ...developed noninvasive predictive models for EO-CRC and investigated its risk factors.
This retrospective multicenter study collected information on 1756 patients (811 patients with EO-CRC and 945 healthy controls) from two medical centers in China. Sociodemographic features, clinical symptoms, medical and family history, lifestyle, and dietary factors were measured. Patients from one cohort were randomly assigned (8:2) to two groups for model establishment and internal validation, and another independent cohort was used for external validation. Multivariable logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost) were performed to establish noninvasive predictive models for EO-CRC. Some variables in the model influenced EO-CRC occurrence and were further analyzed. Multivariable logistic regression analysis yielded adjusted odd ratios (ORs) and 95% confidence intervals (CIs).
All three models showed good performance, with areas under the receiver operator characteristic curves (AUCs) of 0.82, 0.84, and 0.82 in the internal and 0.78, 0.79, and 0.78 in the external validation cohorts, respectively. Consumption of sweet (OR 2.70, 95% CI 1.89-3.86, P < 0.001) and fried (OR 2.16, 95% CI 1.29-3.62, P < 0.001) foods ≥3 times per week was significantly associated with EO-CRC occurrence.
We established noninvasive predictive models for EO-CRC and identified multiple nongenetic risk factors, especially sweet and fried foods. The model has good performance and can help predict the occurrence of EO-CRC in the Chinese population.
Dense and nanostructured YSZ-ZrC composite coatings were reactively synthesized by atmospheric plasma spraying. Reactive YSZ-Al-SiC precursors with different YSZ contents were used and the evolution ...of the phase, microstructure and mechanical properties of the as-prepared coatings were fully revealed. Phase transformation for the YSZ component, from tetragonal phase in the start material to cubic phase in the composite coating, was validated by experimental evidences. It could be explained that the progression of in-situ reactions consumed considerable volume of zirconia and then led to higher Y/Zr ratio of Y-Zr-O melt in the droplets and then cubic phase was retained. Based on the content regulation of the reactive components, the highest yielding of ZrC phase was 35.4 wt% and the highest microhardness and fracture toughness of the composite coatings were 823 HV0.1 and 2.79 MPa/m2.
•Phase transition of YSZ component was observed in Al-YSZ reaction system.•Nanostructured YSZ-ZrC coating was prepared by plasma spraying YSZ-Al-SiC powder.•Effects of precursor regulation on the coating properties were figured out.
A ZrC-ZrSi
2
-Al
2
O
3
powder system was designed and used for preparing ZrC composite coating. Tailored microstructures such as densely packed ZrC-ZrSi
2
whiskers and nanosized alumina grains were ...observed in the coating lamellae. The zirconia derived from the oxidation of zirconium carbide and zirconium silicide during the plasma spraying process contributed to the formation of the near-eutectic alumina-zirconia area. The formation mechanism of the composite coating was discussed based on the characterization of the coating lamellae and the as-prepared coating demonstrated promising mechanical properties due to the coordination of whiskers and eutectic microstructure.
MoSe
2
nanosheets spheres (MoSe
2
·NSs) were synthesized directly on the surface of reduced graphene oxide (rGO) nanosheets (MoSe
2
–rGO) using a simple one-pot hydrothermal approach, which was used ...for supercapacitor. The synergistic effect of the MoSe
2
·NSs and the highly conductive rGO network endows the MoSe
2
–rGO composite excellent electrochemical performance. The effect of the content of graphene in the composite were investigated in details. The optimal electrode exhibits a high specific capacitance of 814.4 F g
−1
at 1 A g
−1
in 2 M KOH. Moreover, the assembled supercapacitor delivers a high specific capacitance of 215.7 F g
−1
at 1 A g
−1
and retains 81.7% of the initial capacitance at 10 A g
−1
after 5000 cycles. It suggests that it has potential as an electrode material for high-performance electrochemical supercapacitors.
FBXW7, a component of the Skp-Cullin1-F-box, mediates target protein recognition. It is a tumor suppressor gene that plays a role in the regulation of cell cycle exit and reentry via c-Myc, c-Jun and ...Notch degradation. There are few studies, particularly involving a large patient cohort, that have evaluated FBXW7 during gastric cancer progression.
Our study aimed to evaluate the value of FBXW7 as a clinical marker in gastric adenocarcinoma (GC) patients including a subset treated with postoperative chemotherapy. Quantitative reverse transcription PCR (qRT-PCR) assay was used to measure FBXW7 transcript levels in tumors paired with normal gastric tissue in 24 gastric adenocarcinoma patients. Subsequently, 546 additional GC samples were evaluated from patients that underwent radical gastrectomy, including 118 early stage cases(Stage I) and 428 advanced stage cases (Stages II or III). Amongst the advanced stage patient cases evaluated, 347 received postoperative adjuvant chemotherapy. All 546 gastric adenocarcinoma cases were then evaluated by tissue microarray and immunohistochemistry (IHC) for FBXW7 expression. Clinicopathological features and diagnoses were confirmed by histopathologic evaluation and review of clinical data. Overall survival (OS) was then evaluated in the 546 gastric cancer patients.
By immunohistologic evaluation, low expression of FBXW7 in primary gastric cancer significantly correlated with poor differentiation of tumor cells. Moreover, low FBXW7 expression was associated with worse survival as well as worse adjuvant chemotherapy response.
Our findings suggest that FBXW7 may serve as an important predictor in chemotherapeutic responses.
AIM：To investigate whether the expression of kallikrein 12（KLK12） is related to the development of gastric cancer（GC） and to determine the role of KLK12 in gastric cancer cells growth,invasion and ...migration.METHODS：Between September 2007 and March 2008,133 patients with histologically confirmed GC were recruited for the study.Expression of KLK12 was detected in samples from GC patients by quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry.The relationship between KLK12 protein expression and clinicopathological features of GC was analyzed.The difference in 5-year survival rates between the high KLK12 protein expression group and the low KLK12 expression group was compared.Additionally,the expression of KLK12 was examined in various human GC cell lines,including MKN-28,SGC-7901 and MKN-45.Small interfering RNA（siRNA） was used to inhibit KLK12 expression in MKN-45 cells.Cell clones stably transfected with KLK12 siRNA were tested for KLK12 expression by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting.Furthermore,a series of functional assays were performed in this study to assess the biological features of transfected cells.Cell proliferation was assessed using the methylthiazolyltetrazoliumassay.Finally,cell migration and invasion were assessed using transwell chamber assays.RESULTS：Of the 133 GC patients included in the study,126（94.7%） showed a higher expression level of KLK12 mRNA when compared to noncancerous tissue specimens.Expression of KLK12 mRNA was significantly higher in GC tissues than in normal tissue（P 〈 0.001）.KLK12 protein expression was detected in 96 of 133（72.2%） GC samples with moderate or strong staining primarily in the cytoplasm.In contrast,negative immunostaining for KLK12 protein was observed in the corresponding normal gastric mucosal tissue.Overexpression of KLK12 protein was significantly associated with lymph node metastasis（P = 0.001）,histological type（P 〈 0.001） and tumor-node-metastasis stage（P = 0.005）,while no significant correlation was observed between expression of KLK12 protein and sex,age,depth of invasion,tumor size or lymphatic invasion.Furthermore,patients with high KLK12 expression had a significantly poorer 5-year survival rate than those with low KLK12 expression（P = 0.002）.Expression of KLK12 mRNA was significantly higher in MKN-45 GC cells compared to normal mucosal cells or two other GC cell lines（P 〈 0.01）.Expression of KLK12 in MKN-45 cells was downregulated after transfection with siRNA.Knockdown of KLK12 markedly decreased the proliferation of MKN-45 cells when compared with parent or mock-transfected cells（P = 0.001）,especially from the 3rd to the 5th day of the assay.In migration assays,fewer KLK12 siRNA cells migrated through the chambers（22.00 ± 1.81） when compared to the parent（46.47 ± 2.42） or mock-transfected cells（45.40 ± 1.99）;these differences were statistically significant（P 〈 0.001）.However,in the invasion assay,the number of KLK12 siRNA cells that invaded the chambers was 18.40 ± 1.12,closely similar to both the parent（18.67 ± 0.98） and mock-transfected cells（18.53 ± 0.92）.There was no significantly difference between the three groups in the invasion assay（P = 0.054）.CONCLUSION：The KLK12 gene is markedly overexpressed in GC tissue,and its expression status may be a powerful prognostic indicator for patients with GC.KLK12 might serve as a novel diagnosis and prognosis biomarker in GC.
Objective
Previous studies have indicated that neurotransmitters play important roles in the occurrence and development of gastric cancer. MAOA is an important catecholamine ...neurotransmitter-degrading enzyme involved in the degradation of norepinephrine, epinephrine and serotonin. To find a potential therapeutic target for the treatment of gastric cancer, the biological functions of MAOA and the underlying mechanism in gastric cancer need to be explored.
Methods
The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets, Kaplan‒Meier (KM) plotter were used to identify the differentially expressed genes, which mainly involved the degradation and synthesis enzymes of neurotransmitters in gastric cancer. We also investigated the expression pattern of MAOA in human and mouse tissues and cell lines by immunohistochemistry and Western blotting analysis. Western blotting, quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA) and a Seahorse experiment were used to identify the molecular mechanism of cancer cell glycolysis. MAOA expression and patient survival were analysed in the Ren Ji cohort, and univariate and multivariate analyses were performed based on the clinicopathological characteristics of the above samples.
Results
MAOA expression was significantly downregulated in gastric cancer tissue and associated with poor patient prognosis. Moreover, the expression level of MAOA in gastric cancer tissue had a close negative correlation with the SUXmax value of PET-CT in patients. MAOA suppressed tumour growth and glycolysis and promoted cancer cell apoptosis. We also reported that MAOA can interact with NDRG1 and regulate glycolysis through suppression of the PI3K/Akt/mTOR pathway. MAOA expression may serve as an independent prognostic factor in gastric cancer patients.
Conclusions
MAOA attenuated glycolysis and inhibited the progression of gastric cancer through the PI3K/Akt/mTOR pathway. Loss of function or downregulation of MAOA can facilitate gastric cancer progression. Overexpression of MAOA and inhibition of the PI3K/Akt/mTOR pathway may provide a potential method for gastric cancer treatment in clinical therapeutic regimens.
Abstract Gastric cancer is one of the most common cancers in China. In the past decade, with the developments in surgical instruments and technologies, minimally invasive surgery has rapidly become ...an accepted treatment for gastric cancer in China. Many Chinese surgeons and researchers have contributed to the rapid evolution of minimally invasive surgery for gastric cancer. Their efforts have transformed into unique laparoscopic technique, workshops, academic communications, education and international communications in China. Meanwhile, many retrospective comparative trials and randomized controlled trials have revealed the advantages in minimally invasive surgery for gastric cancer. However, multicenter randomized controlled trials are still needed to delineate significantly quantifiable differences between laparoscopic and open gastrectomy. With more and more experience has accumulated, laparoscopic gastrectomy has been performed on older and overweight patients. Moreover, advanced minimally invasive techniques, such as modified laparoscopic spleen-preserving splenic hilum lymphadenectomy, various laparoscopic gastric reconstruction methods and robotic gastrectomy have been developed. It seems that China owns the potential to keep up with her neighbor, Japan and Korea, to become one of leading countries utilizing minimally invasive surgery for gastric cancer.
BACKGROUNDTumor budding, is a promising prognostic hallmark in many cancers, and can help us better assess the degree of malignancy in gastric cancer (GC) and in colorectal cancer. In the past few ...years, several articles on the relationship between tumor budding and GC have been published, but different results have been observed. As the relationship between tumor budding and GC remains controversial, we integrated the data from 7 eligible studies to conduct a systematic review and meta-analysis. AIMTo systematically evaluate the prognostic and pathological impact of tumor budding in GC. METHODSLiterature searches were conducted in the PubMed, Cochrane Library, EMBASE and Web of Science databases, and 7 cohort studies involving 2178 patients met our criteria and included in the analysis. The patients were divided into those with high-grade tumor budding and those with low-grade tumor budding, and the cut-off values for tumor budding varied across the included studies. The hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to estimate the impact of tumor budding on overall survival (OS) in GC patients. The odds ratios (ORs) with 95%CIs were used to determine the correlation between tumor budding and pathological parameters (tumor stage, tumor differentiation, lymphovascular invasion, lymph node metastasis) of GC. RESULTSSeven studies involving 2178 patients were included in the meta-analysis. The combined ORs suggested that high-grade tumor budding was significantly associated with tumor stage (OR = 6.63, 95%CI: 4.01-10.98, P < 0.01), tumor differentiation (OR = 3.74, 95%CI: 2.68-5.22, P < 0.01), lymphovascular invasion (OR = 7.85, 95%CI: 5.04-12.21, P < 0.01), and lymph node metastasis (OR = 5.75, 95%CI: 3.20-10.32, P < 0.01). Moreover, high-grade tumor budding predicted a poor 5-year OS (HR = 1.79, 95%CI: 1.53-2.05, P < 0.01) in patients with GC and an adverse 5-year OS (HR = 1.93, 95%CI: 1.45-2.42, P < 0.01) in patients with intestinal-type GC. CONCLUSIONHigh-grade tumor budding suggested a poor prognosis in patients with GC or intestinal-type GC.
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