Prognostic Factor In Gastric Cancer Research Articles

Nomogram Based on Body Composition and Prognostic Nutritional Index Predicts Survival After Curative Resection of Gastric Cancer

This study aimed to identify independent prognostic factors for gastric cancer (GC) patients after curative resection using quantitative computed tomography (QCT) combined with prognostic nutritional index (PNI), and to develop a nomogram prediction model for individualized prognosis. This study retrospectively analyzed 119 patients with GC who underwent curative resection from January 2016 to March 2018. The patients' preoperative clinical pathological data were recorded, and all patients underwent QCT scans before and after curative resection to obtain QCT parameters: bone mineral density (BMD), skeletal muscle area (SMA), visceral fat area (VFA), subcutaneous fat area (SFA) and CT fat fraction (CTFF), then relative rate of change in each parameter (ΔBMD, ΔSMA, ΔVFA, ΔSFA, ΔCTFF) was calculated after time normalization. Multivariate Cox proportional hazards was used to establish a nomogram model that based on independent prognostic factors. The concordance index (C-index), area under the time-dependent receiver operating characteristic (ROC) curve and clinical decision curve were used to evaluate the predictive performance and clinical benefit of the nomogram model． RESULTS: This study found that ΔCTFF, ΔVFA, ΔBMD and PNI are independent prognostic factors for overall survival (OS)(hazard ratio: 1.034, 0.895, 0.976, 2.951, respectively, all p<0.05). The established nomogram model could predict the area under the ROC curveof OS at 1, 3and 5 years as 0.816, 0.815 and 0.881, respectively. The C-index was 0.743 (95% CI, 0.684-0.801), and the decision curve analysis showed that this model has good clinical net benefit. The nomogram model based on body composition and PNI is reliable in predicting the individualized survival of underwent curative resection for GC patients.

Risk factors and clinical significances for retropancreatic lymph node metastasis in gastric cancer patients.

The incidence of retropancreatic lymph node metastasis in gastric cancer patients is not negligible. The aim of present study was to determine the risk factors for retropancreatic lymph node (LN) metastasis and to investigate its clinical significance. Clinical pathologic data of 237 patients with gastric cancer between June 2012 and June 2017 were analyzed retrospectively. 14 patients (5.9%) had retropancreatic LN metastases. The median survival of patients with and without retropancreatic LN metastasis was 13.1 and 25.7 months. According to univariate analysis; tumor size ≥ 8 cm, Bormann type III/IV, undifferentiated type, presence of angiolymphatic invasion, depth of invasion (pT4), N3 stage, No. 3, No. 7, No. 8, No. 9, and No. 12p LN metastasis was found to be associated with retropancreatic LN metastasis. According to multivariate analysis; tumor size ≥ 8 cm, Bormann type III/IV, undifferentiated type, pT4, N3 stage, No. 9 LN metastasis, and No. 12p LN metastasis were found to be independent prognostic variables for retropancreatic LN metastasis. Retropancreatic LN metastasis is a poor prognostic factor for gastric cancer. Tumor size (≥ 8 cm), Bormann type III/IV, undifferentiated tumor, pT4, N3 stage, and No. 9 and No. 12p LN metastasis are risk factors for metastasis to retropancreatic lymph node.

GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

Glutamate-ammonia ligase (GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

Postoperative ratio of C-reactive protein to albumin is an independent prognostic factor for gastric cancer

ObjectiveThe role of postoperative of the ratio of c-reactive protein to albumin (CRP/Alb ratio) in the prognosis of gastric cancer is rarely evaluated. Our purpose was to investigate the correlation of the postoperative CRP/Alb ratio and long-term prognosis of gastric cancer.MethodsWe enrolled 430 patients who suffered from radical gastrectomy. The commonly used inflammatory indices, clinical-pathological characteristics and oncologic outcomes were recorded. The median was used to the cut-off value for preoperative and postoperative CRP/Alb ratio, respectively. Kaplan–Meier analysis and Cox proportional hazards regression model were performed to determine its prognostic significance.ResultsIn univariate analysis, there were significant differences were observed in overall survival (OS) according to perioperative CRP/Alb ratio, c-reactive protein (CRP), serum albumin (Alb), respectively. According to the multivariate analysis, higher postoperative CRP/Alb ratio (HR 2.03, 95% CI 1.55–2.66, P < 0.001), lower postoperative albumin (Alb), higher preoperative c-reactive protein (CRP) and higher postoperative CRP were indicated a shorter overall survival.ConclusionPostoperative inflammatory factors in patients with gastric cancer should be pay attention, especially postoperative CRP/Alb ratio may be an independent predictor of long-term prognosis of gastric cancer.

Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

Application and significance of circRNA and high throughput sequencing in different metastatic pathways of gastric cancer

In this study, we will explore the expression profile of circular RNA (cRNA) in gastric cancer tissues and plasma in order to evaluate its potential as a molecular marker for the detection of gastric cancer. Additionally, we will research the expression profile of cRNA in normal gastric tissue. Reverse transcription drop digital polymerase chain reaction (RT ddPCR), circRNA expression profiling, the prediction of circRNA-microRNA interactions, the design of a method for RT ddPCR, as well as the analysis of clinicopathological factors and survival outcomes are all included in the recommended approach. The results of the research indicate that some circRNAs have a distinct expression pattern in the plasma and tissues of patients with gastric cancer. In addition, a quantitative RT ddPCR approach was created, and the identification of certain circRNAs that are connected with clinicopathological factors and prognosis was accomplished. The results of this study provide significant new insights into the ability of circRNAs to function not only as diagnostic markers but also as independent prognostic factors for gastric cancer. In addition, a dye-based RT ddPCR method is shown to be an effective and economical technique for the detection of plasma circRNA.

The high expression of glial cell line-derived neurotrophic factor receptor alpha Ⅱ (GFRA2) as a predictor of poor prognosis in gastric cancer patients: A survival and regression analysis approach

Gastric cancer has high mortality rates worldwide. Therefore, there is a need to identify prognostic biomarkers. This study evaluated the association between GFRA2 expression levels with clinicopathological features and prognosis in gastric cancer using data extracted from The Cancer Genome Atlas (TCGA) database and a series of algorithms. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to analyze the association between different clinical features and survival. Single-sample gene set enrichment analysis (GSEA) was used to examine the correlation between GFRA2 expression and immune infiltration. The results showed that the expression of GFRA2 in tumor samples was significantly lower than that in normal samples. High expression of GFRA2 was significantly associated with histological type, histologic grade, and worse overall survival, disease-specific survival, and progression-free survival. The univariate Cox analysis showed that the expression of GFRA2 was significantly correlated with T stage, N stage, M stage, and age. The multivariate analysis identified GFRA2 expression as an independent prognostic factor for gastric cancer. GSEA showed that GFRA2 might regulate the calcium signaling pathway, focus adhesion, olfactory conduction, the extracellular matrix glycoproteins, and response to the Leishmania parasitic infection. GFRA2 showed a significant moderate positive correlation with the infiltration of mast cells. In summary, a high expression of GFRA2 may contribute to poor survival in gastric cancer patients and could be used as a potential prognostic biomarker.

Analysis and application of RNA binding protein gene pairs to predict the prognosis of gastric cancer

BackgroundRNA-binding proteins (RBPs) are closely related to tumors, but little is known about the mechanism of RBPs in tumorigenesis and progression of gastric cancer (GC). As genes do not usually act alone in the pathway deregulation, gene pair combinations are more likely to become stable and accurate biomarkers. The purpose of our research is to establish a novel signature based on RBP gene pairs to predict the prognosis of gastric cancer patients. MethodsWe downloaded genetic and clinical information from the TCGA and GEO database. TCGA and GSE13911 were used for screening differentially expressed genes (DEGs). The RBP genes were gathered from previous studies and employed to screen out DE-RBP genes after intersecting with DEGs. Samples were classified according to the relative expression of each pair of DE-RBP genes. The univariate Cox regression analysis and random forest were used to identify hub gene pairs to construct signature for predicting the prognosis of gastric cancer. Time-dependent ROC curves and KM survival curves were performed to evaluate the signature. GSEA was performed in TCGA training cohort and GSE62254 testing cohort to analyze enrichment pathways. Finally, the influence of these gene pairs on the prognosis of GC patients was further elucidated respectively through the combination of high and low expression of the two genes in each hub gene pair. ResultsWe screened out 6 hub RBP gene pairs (COL5A2/FEN1, POP1/GFRA1, EXO1/PLEKHS1, SLC39A10/CHI3L1, MMP7/PPP1R1 B and SLC5A6/BYSL) to predict the prognosis of patients with gastric cancer. Using the optimal cut-off value to divide patients into high-risk and low-risk groups in the training and testing cohort, we found that the overall survival (OS) of the low-risk group was higher than that of the high-risk group (P < 0.05). The area under the ROC curves for 1, 3, and 5 years were (0.659, 0.744, 0.758) and (0.624, 0.650, 0.653) in two cohorts. Univariate and multivariate Cox regression analysis showed that 6 RBP gene pairs signature were independent prognostic factors for gastric cancer (P < 0.05). In addition, the prognostic survival analysis showed that COL5A2-high/FEN1-low, POP1-low/GFRA1-high, EXO1-low/PLEKHS1-low,SLC39A10-high/CHI3L1-low, MMP7-high/PPP1R1 B-low, SLC5A6-low/BYSL-low had worse OS (P < 0.05). And the gene correlation analysis showed that there was no obvious correlation between the genes in each gene pairs except SLC5A6/BYSL and POP1/GFRA1. Finally, GSEA analysis showed that the high-risk group was enriched in tumor migration, invasion and growth-related pathways. ConclusionOur study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy.

The Challenges of Gastric Cancer Surgery during the COVID-19 Pandemic.

The aim of this study was to quantify the impact of the COVID-19 pandemic on the surgical treatment of patients with gastric cancer. Data from patients undergoing surgery for gastric cancer during the pandemic were analyzed and the results obtained were compared with the corresponding periods of 2016-2017 and 2018-2019. Various parameters were taken into consideration and their dynamics highlight significant changes in the pandemic year compared with the two pre-pandemic periods. Statistical analysis revealed a marked decrease in the number of surgeries performed during the pandemic (p < 0.001). Severe prognostic factors for gastric cancer, including weight loss and upper gastrointestinal hemorrhage, were associated with an increased number of postoperative fistulas, while emesis was statistically correlated with a more advanced cancer stage (p < 0.011). There was also a reduction in the total duration of hospitalization (p = 0.044) and postoperative hospitalization (p = 0.047); moreover, the mean duration of surgical intervention was higher during the pandemic (p = 0.044). These findings provide evidence for the significant changes in clinical and therapeutic strategies applied to patients undergoing surgery for gastric cancer during the study period. The ongoing pandemic has exerted a substantial and complex impact, the full extent of which remains yet to be fully comprehended.

Prognostic and predictive values of the grading system of lymph node status in patients with advanced-stage gastric cancer.

Lymph node metastasis is one of the most important prognostic factors of gastric cancer. However, the effect of germinal centers in lymph nodes on the prognosis of patients with gastric cancer has not been reported. This study aimed to investigate the contribution of germinal center generation to prognostic parameters and clinicopathological significance in gastric cancer. We retrospectively reviewed gastric cancer patients who underwent surgery from October 2012 to June 2022. We analyzed 5484 lymph nodes (210 patients) and calculated the lymph node metastasis rate (LNMR) and the proportion of non-metastatic lymph nodes containing three or more germinal centers (NML-GCP). Using a grading system that incorporated LNMR and NML-GCP. The tumors were classified into three groups based on this system, which was found to be significantly associated with prognosis. The TNM stage and grading system of lymph node status were independent risk factors for overall survival (OS) and disease-free survival (DFS). The 5-year OS rates for patients with advanced gastric cancer were 85.07% (n=50), 58.34% (n=42), and 24.44% (n=21) for Grades 1, 2, and 3, respectively (p<0.0001). The 5-year DFS rates were 65.32% (n=58), 40.85% (n=51), and 5.88% (n=34), respectively (p<0.0001). Patients with Grade 1 advanced gastric cancer had higher 5-year OS and DFS rates compared to those with Grade 2 or 3 in TNM stage II and III. Furthermore, the 5-year OS and DFS rates differed significantly among patients with different grades of advanced gastric cancer who received chemotherapy (p<0.0001). These findings suggest that the grading system may be valuable for predicting prognosis and guiding clinical management in patients with gastric cancer, and provides good prognostic stratification for OS and DFS in patients with TNM stage II and III.

HNF4A-BAP31-VDAC1 axis synchronously regulates cell proliferation and ferroptosis in gastric cancer

B cell receptor associated protein 31 (BAP31) is closely associated with tumor progression, while the role and mechanism of BAP31 in gastric cancer (GC) remains unknown. This study explored that BAP31 was upregulated in GC tissues and high expression indicated poor survival of GC patients. BAP31 knockdown inhibited cell growth and induced G1/S arrest. Moreover, BAP31 attenuation increased the lipid peroxidation level of the membrane and facilitated cellular ferroptosis. Mechanistically, BAP31 regulated cell proliferation and ferroptosis by directly binding to VDAC1 and affected VDAC1 oligomerization and polyubiquitination. HNF4A was bound to BAP31 at the promoter and increased its transcription. Furthermore, knockdown of BAP31 inclined to make GC cells vulnerable to 5-FU and ferroptosis inducer, erastin, in vivo and in vitro. Our work suggests that BAP31 may serve as prognostic factor for gastric cancer and act as potential therapeutic strategy for gastric cancer.

Glycosyltransferase GLT8D1 and GLT8D2 serve as potential prognostic biomarkers correlated with Tumor Immunity in Gastric Cancer

BackgroundGlycosylation involved in various biological function, aberrant glycosylation plays an important role in cancer development and progression. Glycosyltransferase 8 domain containing 1 (GLT8D1) and GLT8D2, as members of the glycosyltransferase family proteins, are associated with transferase activity. However, the association between GLT8D1/2 and gastric cancer (GC) remains unclear. We aimed to investigate the potential prognostic value and oncogenic role of GLT8D1/2 in GC.MethodsThe relationship between GLT8D1/2 and GC was evaluated through comprehensive bioinformatics approaches. A series of factors like gene expression patterns, Kaplan-Meier survival analyses, Cox regression analyses, prognostic nomogram, calibration curves, ROC curves, function enrichment analyses, tumor immunity association, genetic alterations, and DNA methylation were included. Data and statistical analyses were performed using R software (v3.6.3).ResultsBoth GLT8D1 and GLT8D2 expression were significantly upregulated in GC tissues(n = 414) compared with normal tissues(n = 210), and high expression of GLT8D1/2 was remarkably correlated with poor prognosis for GC patients. Cox regression analyses implied that GLT8D1/2 could act as independent prognostic factors in GC. Furthermore, gene function analyses indicated that multiple signaling pathways involving tumor oncogenesis and development enriched, such as mTOR, cell cycle, MAPK, Notch, Hedgehog, FGF, and PI3K-Akt signaling pathways. Moreover, GLT8D1/2 was significantly associated with immune cell infiltration, immune checkpoint genes, and immune regulators TMB/MSI.ConclusionGLT8D1/2 may serve as potential prognostic markers of poor prognosis in GC correlated with tumor immunity. The study provided an insight into identifying potential biomarkers and targets for prognosis, immunotherapy response, and therapy in GC.

Updates on global epidemiology, risk and prognostic factors of gastric cancer.

Gastric cancer (GC) is defined as the primary epithelial malignancy derived from the stomach, and it is a complicated and heterogeneous disease with multiple risk factors. Despite its overall declining trend of incidence and mortality in various countries over the past few decades, GC remains the fifth most common malignancy and the fourth leading cause of cancer-related death globally. Although the global burden of GC has shown a significant downward trend, it remains severe in certain areas, such as Asia. GC ranks third in incidence and mortality among all cancer types in China, and it accounts for nearly 44.0% and 48.6% of new GC cases and GC-related deaths in the world, respectively. The regional differences in GC incidence and mortality are obvious, and annual new cases and deaths are increasing rapidly in some developing regions. Therefore, early preventive and screening strategies for GC are urgently needed. The clinical efficacies of conventional treatments for GC are limited, and the developing understanding of GC pathogenesis has increased the demand for new therapeutic regimens, including immune checkpoint inhibitors, cell immunotherapy and cancer vaccines. The present review describes the epidemiology of GC worldwide, especially in China, summarizes its risk and prognostic factors, and focuses on novel immunotherapies to develop therapeutic strategies for the management of GC patients.

Quantitative parameters in novel spectral computed tomography: Assessment of Ki-67 expression in patients with gastric adenocarcinoma.

The level of Ki-67 expression has served as a prognostic factor in gastric cancer. The quantitative parameters based on the novel dual-layer spectral detector computed tomography (DLSDCT) in discriminating the Ki-67 expression status are unclear. To investigate the diagnostic ability of DLSDCT-derived parameters for Ki-67 expression status in gastric carcinoma (GC). Dual-phase enhanced abdominal DLSDCT was performed preoperatively in 108 patients with gastric adenocarcinoma. Primary tumor monoenergetic CT attenuation value at 40-100 kilo electron volt (kev), the slope of the spectral curve (λHU), iodine concentration (IC), normalized IC (nIC), effective atomic number (Zeff) and normalized Zeff (nZeff) in the arterial phase (AP) and venous phase (VP) were retrospectively compared between patients with low and high Ki-67 expression in gastric adenocarcinoma. Spearman's correlation coefficient was used to analyze the association between the above parameters and Ki-67 expression status. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic efficacy of the statistically significant parameters between two groups. Thirty-seven and 71 patients were classified as having low and high Ki-67 expression, respectively. CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, and Zeff-related parameters were significantly higher, but IC-related parameters were lower in the group with low Ki-67 expression status than the group with high Ki-67 expression status, and other analyzed parameters showed no statistical difference between the two groups. Spearman's correlation analysis showed that CT40 kev-VP, CT70 kev-VP, CT100 kev-VP, Zeff, and nZeff exhibited a negative correlation with Ki-67 status, whereas IC and nIC had positive correlation with Ki-67 status. The ROC analysis demonstrated that the multi-variable model of spectral parameters performed well in identifying the Ki-67 status [area under the curve (AUC) = 0.967; sensitivity 95.77%; specificity 91.89%)]. Nevertheless, the differentiating capabilities of single-variable model were moderate (AUC value 0.630 - 0.835). In addition, the nZeff VP and nICVP (AUC 0.835 and 0.805) showed better performance than CT40 kev-VP, CT70 kev-VP and CT100 kev-VP (AUC 0.630, 0.631 and 0.662) in discriminating the Ki-67 status. Quantitative spectral parameters are feasible to distinguish low and high Ki-67 expression in gastric adenocarcinoma. Zeff and IC may be useful parameters for evaluating the Ki-67 expression.

PTPN14 promotes gastric cancer progression by PI3KA/AKT/mTOR pathway

Gastric cancer is a high molecular heterogeneous disease with a poor prognosis. Although gastric cancer is a hot area of medical research, the mechanism of gastric cancer occurrence and development is still unclear. New strategies for treating gastric cancer need to be further explored. Protein tyrosine phosphatases play vital roles in cancer. A growing stream of studies shows that strategies or inhibitors targeting protein tyrosine phosphatases have been developed. PTPN14 belongs to the protein tyrosine phosphatase subfamily. As an inert phosphatase, PTPN14 has very poor activity and mainly functions as a binding protein through its FERM (four-point-one, ezrin, radixin, and moesin) domain or PPxY motif. The online database indicated that PTPN14 may be a poor prognostic factor for gastric cancer. However, the function and underlying mechanism of PTPN14 in gastric cancer remain unclear. We collected gastric cancer tissues and detected the expression of PTPN14. We found that PTPN14 was elevated in gastric cancer. Further correlation analysis indicated that PTPN14 was relevant with the T stage and cTNM (clinical tumor node metastasis classification) stage. The survival curve analysis showed that gastric cancer patients with higher PTPN14 expression had a shorter survival time. In addition, we illustrated that CEBP/β (CCAAT enhanced binding protein beta) could transcriptionally activate PTPN14 expression in gastric cancer. The highly expressed PTPN14 combined with NFkB (nuclear factor Kappa B) through its FERM domain and accelerated NFkB nucleus translocation. Then, NFkB promoted the transcription of PI3KA and initiated the PI3KA/AKT/mTOR pathway to promote gastric cancer cell proliferation, migration, and invasion. Finally, we established mice models to validate the function and the molecular mechanism of PTPN14 in gastric cancer. In summary, our results illustrated the function of PTPN14 in gastric cancer and demonstrated the potential mechanisms. Our findings provide a theoretical basis to better understand the occurrence and development of gastric cancer.

Prognostic Significance of Degree of Anaemia and Blood Transfusions in Gastric Cancer Patients

Background: Anaemia is a common complication of many solid tumours and occurs in approximately 41 % of patients with advanced gastric cancer at the time of diagnosis. Studies have shown that anaemia is an independent prognostic factor in gastric cancer, however it is less clear if blood transfusion alters the outcome in these patients. Aim of this study is to evaluate the effect of anaemia and blood transfusion on survival in advanced gastric cancer patients at our institution. Methods: This is a retrospective review of electronic medical records of gastric cancer patients treated from January to December 2013. Patients' demographics and clinical data was collected and analysed in relation to various factors including level of haemoglobin and use of blood transfusion. Survival was calculated using Univariate, multivariate and Kaplan-Meier survival analysis. Results: A total of 112 patients were identified including 79 (70%) males and 33 (30%) females with a median age of 73 years. Vast majority (n=88, 79%) of patients had locally advanced (T4 or node positive) disease at initial presentation. Eighty-three patients did not proceed to surgery after neoadjuvant chemotherapy due to inoperable disease. Initial Haemoglobin was &gt;100 gram per litre in 28 (25%) patients. Nineteen patients had Haemoglobin of &lt;80 gram per litre. 96 (86%) patients received blood transfusion. Overall, 98 (87.5%) patients died. The estimated median overall survival was 12 months (95% CI=11-81; SD=17). The 1-, 3-, and 5-years OS were 55%, 30% and 10% respectively. The median progression free survival (PFS) with any treatment was 10 months (SD=20). Univariate analysis showed statistical significance of level of Hb and surgical resection to overall survival (P=0.0122 and P=0.0001). Multivariate analysis showed disease stage, surgical resection and Hb level as independent factors to the outcome. Conclusion: The point prevalence of anaemia in our gastric cancer patients during treatment had an effect on overall survival. The outcome couldn't be improved with blood transfusion. Our findings indicate the need for a consistent diagnostic and treatment approach to anaemia in this setting.

MiR-199a-3p promotes gastric cancer progression by promoting its stemness potential via DDR2 mediation

BackgroundPeritoneal metastasis (PM) is an independent prognostic factor in gastric cancer (GC), however, the underlying mechanisms of PM occurrence remain unclear. MethodThe roles of DDR2 were investigated in GC and its potential relationship to PM, and orthotopic implants into nude mice were performed to assess the biological effects of DDR2 on PM. ResultsHerein, DDR2 level is more significantly observed to elevate in PM lesion than the primary lesion. GC with DDR2-high expression evokes a worse overall survival (OS) in TCGA, similar results of the gloomy OS with high DDR2 levels are clarified via the stratifying stage of TNM. The conspicuously increased expression of DDR2 was found in GC cell lines, luciferase reporter assays verified that miR-199a-3p directly targeted DDR2 gene, which was correlated to tumor progression. We ulteriorly observed DDR2 participated in GC stemness maintenance via mediating pluripotency factor SOX2 expression and implicated in autophagy and DNA damage of cancer stem cells (CSCs). In particular, DDR2 dominated EMT programming through recruiting NFATc1-SOX2 complex to Snai1 in governing cell progression, controlling by DDR2-mTOR-SOX2 axis in SGC-7901 CSCs. Furthermore, DDR2 promoted the tumor peritoneal dissemination in gastric xenograft mouse model. ConclusionPhenotype screens and disseminated verifications incriminating in GC exposit the miR-199a-3p-DDR2-mTOR-SOX2 axis as a clinically actionable target for tumor PM progression. The herein-reported DDR2-based underlying axis in GC represents novel and potent tools for studying the mechanisms of PM.

CircIPO7 dissociates caprin-1 from ribosomes and inhibits gastric cancer cell proliferation by suppressing EGFR and mTOR

Circular RNA (circRNA) is a novel RNA molecule characterized by covalently closed loop structure. Since its discovery, researchers have shown that circRNA is not “splicing noise” but a participant of various pathophysiological processes through unique mechanisms. circIPO7, which was identified as an independent prognostic factor in gastric cancer (GC) patients, was downregulated in GC tissues and cells compared to paracarcinoma tissues and normal epithelial cells. circIPO7 overexpression significantly suppressed GC cell proliferation in vitro and in vivo. Mechanistically, circIPO7 directly binds with caprin-1, an RNA-binding protein involved in mRNA translation, sharing overlapping binding sites with G3BP1. Thus, the complex containing overexpressed circIPO7 blocked the caprin-1-G3BP1 interaction and dissociated caprin-1 and its target mRNAs (EGFR and mTOR) from ribosomes, resulting in their translational inhibition, followed by PI3K/AKT/mTOR pathway inactivation. We uncovered a novel molecular mechanism for circRNAs in GC development, identifying circIPO7 as a potential target for cancer treatment.

Predictive significance of surgery-induced lymphopenia on the survival after curative resection for locally advanced gastric cancer: a retrospective cohort analysis

BackgroundFollowing the establishment of the anti-cancer effect of immune checkpoint inhibitors, lymphopenia has attracted attention as a parameter of preexisting cancer-related immune tolerance. Although the pretreatment absolute lymphocyte count (ALC) has been reported as a prognostic factor in gastric cancer patients, the impact of perioperative changes in the ALC remains unknown. The aim of the present study was to explore the relationship between surgery-induced lymphopenia and outcome.MethodsDatabase entries for 584 patients who underwent curative resections for pathological Stage IB-III gastric cancer were reviewed. We retrospectively compared clinicopathological factors including pretreatment ALC (pre-ALC) and ALC at first visit after discharge (post-ALC) with the survival. The low ALC was defined as < 1000/μL.ResultsThe ALC decreased significantly at 1 and 3 days after surgery and then recovered to the baseline value. A low pre-ALC (p < 0.001) and a low post-ALC (p < 0.001) were both correlated with a poor relapse-free survival (RFS). A multivariate analysis of RFS identified a low post-ALC (hazard ratio 1.875, 95% CI 1.156–3.402, p = 0.01), age, gender, BMI, T disease, N disease, severe vessel invasion, type of gastrectomy and postoperative morbidity as independent factors. The low post-ALC group had a poor RFS among patients with Stage II (p = 0.04) and Stage III (p = 0.04) disease, but not among patients with Stage IB disease (p = 0.13). Consistently, the overall survival (OS) rate was significantly lower among patients with a low post-ALC for all stage (p < 0.001), stage II (p = 0.02) and stage III (p = 0.01) disease, not for stage IB (p = 0.09). A low post-ALC was identified as an independent factor for predicting OS by multivariate analysis (hazard ratio: 2.275, 95% CI 1.373–3.769, p = 0.01).ConclusionsA decrease in post-ALC was correlated with both of RFS and OS after curative resection in patients with locally advanced gastric cancer.HighlightsPostoperative lymphopenia was a poor prognostic factor for gastric cancer.

LncRNA TRHDE-AS1 and MiR-1275 as Promising Prognostic Biomarkers and Effects on Tumor Cell Progression in Gastric Cancer.

Gastric cancer is a common malignant tumor with a relatively poor prognosis after surgery. Non-coding RNA may serve as biomarkers for the progression and prognosis of various cancers. The clinical significance and biological function of lncRNA TRHDE-AS1 and miR-1275 in gastric cancer were assessed in this study. 119 paired tissues were selected with adequate clinical information. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression level of lncRNA TRHDE-AS1 and miR-1275 in gastric cancer tissues and cells. The association between lncRNA TRHDE-AS1 or miR-1275 expression and the clinicopathological features of patients was analyzed by the Pearson Chi-square test. Kaplan-Meier analysis and Multi-variate Cox proportional regression analysis were utilized to evaluate the prognostic value of lncRNA TRHDE-AS1 and miR-1275. Finally, the effect of TRHDE-AS1 binding to miR-1275 on the gastric cancer cellular process was investigated by CCK-8 and Transwell assay. LncRNA TRHDE-AS1 was found to be downregulated in gastric cancer tissues and cells, but miR-1275 upregulated, which both showed significant associations with clinical pathology of gastric cancer patients (including TNM stage and lymph node metastasis) and a poor prognosis. LncRNA TRHDE-AS1 and miR-1275 can be considered two independent prognostic factors for gastric cancer. Furthermore, the upregulation of lncRNA TRHDE-AS1 inhibited cell proliferation, migration, and invasion of gastric cancer partly by miR-1275. LncRNA TRHDE-AS1/miR-1275 axis may be involved in the progression of gastric cancer and can be promising prognostic factors, which may provide new insights into the treatment of gastric cancer.