Indicator In Gastric Cancer Research Articles

YY1: a key regulator inhibits gastric cancer ferroptosis and mediating apatinib-resistance

ObjectiveGastric cancer (GC) stands as a prevalent and deadly global malignancy. Despite its role as a preoperative neoadjuvant therapy, Apatinib’s effectiveness is curtailed among GC patients exhibiting elevated YY1 expression. YY1’s connection to adverse prognosis, drug resistance, and GC metastasis is established, yet the precise underlying mechanisms remain elusive. This study aims to unravel potential pathogenic pathways attributed to YY1.DesignUtilizing bioinformatics analysis, we conducted differentially expressed genes, functional annotation, and pathway enrichment analyses, and further validation through cellular and animal experiments.ResultsHigher YY1 expression correlated with diminished postoperative progression-free survival (PFS) and disease-specific survival (DSS) rates in TCGA analysis, identifying YY1 as an independent DSS indicator in gastric cancer (GC) patients. Notably, YY1 exhibited significantly elevated expression in tumor tissues compared to adjacent normal tissues. Bioinformatics analysis revealed noteworthy differentially expressed genes (DEGs), transcriptional targets, factors, and co-expressed genes associated with YY1. LASSO Cox analysis unveiled Transferrin as a prospective pivotal protein regulated by YY1, with heightened expression linked to adverse DSS and PFS outcomes. YY1’s role in governing the p53 signaling pathway and ferroptosis in GC cells was further elucidated. Moreover, YY1 overexpression dampened immune cell infiltration within GC tumors. Additionally, YY1 overexpression hindered GC cell ferroptosis and mediated Apatinib resistance via the p53 pathway. Remarkably, IFN-a demonstrated efficacy in reversing Apatinib resistance and immune suppression in GC tissues.ConclusionsOur findings underscore the pivotal role of YY1 in driving GC progression and influencing prognosis, thus pinpointing it as a promising therapeutic target to enhance patient outcomes.

Protocadherin Beta 2 as a Promising Prognostic and Immunotherapeutic Predictive Indicator in Gastric Cancer

Protocadherin Beta 2 as a Promising Prognostic and Immunotherapeutic Predictive Indicator in Gastric Cancer

Immune responses of six-transmembrane epithelial antigen of the prostate 4 functions as a novel biomarker in gastric cancer.

Immune cells play an important role in regulating the behavior of tumor cells. According to emerging evidence, six-transmembrane epithelial antigen of the prostate 4 (STEAP4) performs a crucial part in tumor microenvironmental immune response and tumorigenesis, and serves as the potential target for cellular and antibody immunotherapy. However, the immunotherapeutic role of STEAP4 in gastric cancer (GC) remains unclear. To investigate the expression of STEAP4 in GC and its relationship with immune infiltrating cells, and explore the potential value of STEAP4 as an immune prognostic indicator in GC. The expression level of STEAP4 was characterized by immunohistochemistry in tumors and adjacent non-cancerous samples in 96 GC patients. Tumor Immune Estimation Resource was used to study the correlation between STEAP4 and tumor immune infiltration level and immune infiltration gene signature. R package was used to analyze the relationship between STEAP4 expression and immune and stromal scores in GC (GSE62254) by the ESTIMATE algorithm, and Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis were applied to analyze the effect of STEAP4 on clinical prognosis. Immunohistochemistry analysis showed that STEAP4 expression was higher in GC tissues than in adjacent tissues, and STEAP4 expression was positively correlated with the clinical stage of GC. In GC, the expression of STEAP4 was positively correlated with the infiltration levels of B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. The expression level of STEAP4 was strongly correlated with most of the immune markers. In addition, STEAP4 expression was inversely correlated with tumor purity, but correlated with stromal score (r = 0.43, P < 0.001), immune score (r = 0.29, P < 0.001) and estimate score (r = 0.39, P < 0.001). Moreover, stromal, immune, and estimate scores were higher in the STEAP4 high expression group, whereas tumor purity was higher in the STEAP4 Low expression group. The relationship between STEAP4 expression and prognosis of patients with GC was further investigated, and the results showed that high STEAP4 expression was associated with poor overall survival and disease-free survival. In addition, Kaplan-Meier Plotter showed that high expression of STEAP4 was significantly correlated with poor survival of patients with GC. The current findings suggest an oncogenic role for STEAP4 in GC, with significantly high levels being associated with poor prognosis. Investigation of the GC tumor microenvironment suggests the potential function of STEAP4 is connected with the infiltration of diverse immune cells, which may contribute to the regulation of the tumor microenvironment. In conclusion, STEAP4 may serve as a potential therapeutic target for GC to improve the immune infiltration, as well as serve as a prognostic biomarker for judging the prognosis and immune infiltration status of GC.

High Expression of COL10A1 Is an Independent Predictive Poor Prognostic Biomarker and Associated with Immune Infiltration in Advanced Gastric Cancer Microenvironment

Medical technology has become more and more sophisticated recently, which, however, fails to contribute to a better prognosis for patients suffering advanced gastric cancer (GC). Hence, new biomarkers specific to GC diagnosis and prognosis shall be identified urgently. This study screened differentially expressed genes (DEGs) between 375 GC samples and 32 paracancer tissue samples from TCGA datasets. The expression of Collagen type X alpha 1 (COL10A1) in GC was analyzed. The chi-square test assisted in analyzing the relevance of COL10A1 to the clinicopathologic characteristics. The Kaplan-Meier method helped to assess the survival curves and log-rank tests assisted in the examination of the differences. The Cox proportional hazard regression model served for analyzing the risk factors for GC. Then, we developed a nomogram that contained the COL10A1 expression and clinical information. Finally, how COL10A1 expression was associated with the immune infiltration was also evaluated. In this study, 7179 upregulated and 3771 downregulated genes were identified. Among them, COL10A1 expression was distinctly increased in GC specimens compared with nontumor specimens. High COL10A1 expression exhibited an obvious relation to tumor T and pathologic stage. ROC assays confirmed the diagnostic value of COL10A1 expression in screening GC samples from normal samples. Survival data displayed that patients with high COL10A1 expression exhibited a shorter OS and DSS than those with low COL10A1 expression. We obtained a predictive nomogram, which could better predict the COL10A1 expression by virtue of discrimination and calibration. The prognostic value of COL10A1 expression was further confirmed in GSE84426 datasets. Immune assays revealed that COL10A1 expression was associated with tumor-filtrating immune cells, like CD8 T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, NK CD56dim cells, NK cells, pDC, T helper cells, Tem, Th1 cells, Th17 cells, and Treg. Overall, we firstly proved that COL10A1 may be a novel and valuable prognostic and diagnostic factor for GC patients. In addition, COL10A1 has potential to be an immune indicator in GC.

Intraoperative frozen section analysis of margin status as a quality indicator in gastric cancer surgery.

Positive pathologic margins following gastric cancer (GC) resection carries a poor prognosis. We evaluated intraoperative frozen section (IFS) analysis of resection margins (RMs) as a quality indicator in GC surgery. Patients referred to a provincial cancer agency with surgically resected non-metastatic GC between 2004 and 2012 were included. Associations between IFS analysis, other baseline characteristics, RMs, and overall survival (OS) were assessed using logistic regression, Kaplan-Meier analyses, and Cox proportional hazards modeling. Among 377 patients, median age was 67 years, 68% were male, and 16% had +RMs. Thirty-fourpercentof patients underwent IFS analysis, which protected against +RMs (odds ratio[OR]: 0.34, 95% confidence interval [CI]: 0.16-0.73, p = 0.006) and improved OS (hazards ratio[HR]: 0.72, 95% CI: 0.54-0.98, p = 0.037). OS following re-resection of IFS positive patients was similar to IFS negative patients (69 vs. 54 months, p = 0.317). Stage III disease (OR: 12.8, 95% CI: 3.00-55.0, p = 0.001) and gastroesophageal junction tumors (OR: 2.25, 95% CI: 1.05-4.78, p = 0.036) predicted +RMs. Stage III disease led to worse OS (HR: 2.89, 95% CI: 1.92-4.34, p < 0.001) while intestinal histology improved OS (HR: 0.67, 95% CI: 0.50-0.90, p = 0.007). IFS analysis reduce +RMs and improve OS and should be incorporated in curative intent GC surgery for patients with locally advanced GC.

LncRNA SNHG22 promotes gastric cancer progression by regulating the miR-101-3p/e2f2 axis

ABSTRACT Gastric cancer (GC) still poses a significant threat to human life. Hence, there is an urgent need to understand the mechanism of GC progression and develop novel therapeutics approach to treating GC. This study was conducted to evaluate the role of the lncRNA SNHG22 in the progression of GC. First, GC data from TCGA were analyzed using GEPIA. After the starbase database was used to predict SNHG22 target miRNA and miR-101-3p target mRNA. The predictions were validated using a dual-luciferase reporter assay, biotinylated RNA pull-down assay, and RIP-qRT-PCR. The relative expression of SNHG22, miR-101-3p, and E2F2 was measured by qRT-PCR and western blot (WB) analysis, while the mechanism of GC cell proliferation was elucidated through the colony formation and CCK-8 assay. Our result showed that SNHG22 was upregulated significantly in GC tissue samples from TCGA database, GC cell lines, and clinical tissue samples, and its expression was related to low survival rate of gastric cancer patients. Bioinformatics prediction predicted miR-101-3p as the potential target of SNHG22 and E2F2 genes as miR-101-3p target mRNA. We found that E2F2 expression was negatively associated with overall survival of GC patients. Functional study showed that silencing SNHG22 markedly inhibited the proliferation, migration, and invasion of GC cells as well as in vivo tumor growth. This was reversed after inhibiting miR-101-3p or overexpressing E2F2. The lncRNA SNHG22 promotes the proliferation, migration, and invasion of GC cells via the miR-101-3p/E2F2 axis. SNHG22 might be a potential prognostic indicator in gastric cancer.

FSIP1 Is Associated with Poor Prognosis and Can Be Used to Construct a Prognostic Model in Gastric Cancer.

Gastric cancer (GC) is one of the most common upper gastrointestinal malignant tumors, and the incidence of the GC shows an increasing trend in the past years. Finding more sensitive markers will help to reveal the mechanism of GC progression and clinic diagnoses. This study first analyzed the mRNA expression level of FSIP1 in TCGA GC samples and the significance in predicting the prognosis. KEGG and GO analyses were used to explore the molecular mechanism of FSIP1 in GC progression. This study further retrospectively analyzed 166 clinical samples of GC from Harbin Medical University Cancer Hospital and evaluated the expression level of FSIP1 by immunohistochemistry. Kaplan-Meier and Cox multivariate analysis was used to investigate the prognostic value of FSIP1 expression in GC patients. We also identified correlations between FSIP1 and clinicopathological characteristics. This study found that the mRNA level of FSIP1 was significantly upregulated in GC compared with nontumor specimens and correlated with poor prognosis. Immunohistochemistry confirmed the results of bioinformatics analysis of the TCGA GC database. FSIP1 was associated with pTNM pathological stage, tumor location, and neural invasion. In addition, multivariate Cox regression analysis showed that FSIP1, T classification, and N classification were independent posterior factors of patients and could be combined with pathological features to construct a nomogram prognostic model. Overall, our results suggest that FSIP1 is expected to be an independent prognostic indicator of GC.

Radiomics in Gastric Cancer: First Clinical Investigation to Predict Lymph Vascular Invasion and Survival Outcome Using 18F-FDG PET/CT Images.

BackgroundLymph vascular invasion (LVI) is an unfavorable prognostic indicator in gastric cancer (GC). However, there are no reliable clinical techniques for preoperative predictions of LVI. The aim of this study was to develop and validate PET/CT-based radiomics signatures for predicting LVI of GC preoperatively. Radiomics nomograms were also established to predict patient survival outcomes.MethodsThis retrospective study registered 148 GC patients with histopathological confirmation for LVI status, who underwent pre-operative PET/CT scans (Discovery VCT 64 PET/CT system) from December 2014 to June 2019. Clinic-pathological factors (age, gender, and tumor grade, etc.) and metabolic PET data (maximum and mean standardized uptake value, total lesion glycolysis and metabolic tumor volume) were analyzed to identify independent LVI predictors. The dataset was randomly assigned to either the training set or test set in a 7:3 ratios. Three-dimensional (3D) radiomics features were extracted from each PET- and CT-volume of interests (VOI) singularly, and then a radiomics signature (RS) associated with LVI status is built by feature selection. Four models with different modalities (PET-RS: only PET radiomics features; CT-RS: only CT radiomics features; PET/CT-RS: both PET and CT radiomics features; PET/CT-RS plus clinical data) were developed to predict LVI. Patients were postoperatively followed up with PET/CT every 6-12 months for the first two years and then annually up to five years after surgery. The PET/CT radiomics score (Rad-scores) was calculated to assess survival outcome, and corresponding nomograms with radiomics (NWR) or without radiomics (NWOR) were established.ResultsTumor grade and maximum standardized uptake value (SUVmax) were the independent LVI predictor. 1037 CT and PET 3D radiomics features were extracted separately and reduced to 4 and 5 features to build CT-RS and PET-RS, respectively. PET/CT-RS and PET/CT-RS plus clinical data (tumor grade and SUVmax) were also developed. The ROC analysis demonstrated clinical usefulness of PET/CT-RS plus clinical data (AUC values for training and validation, respectively 0.936 and 0.914) and PET/CT-RS (AUC values for training and validation, respectively 0.881 and 0.854), which both are superior to CT-RS (0.838 and 0.824) and PET-RS (0.821 and 0.812). SUVmax and LVI were independent prognostic indicators of both OS and PFS. Decision curve analysis (DCA) demonstrated NWR outperformed NWOR and was established to assess survival outcomes. For estimation of OS and PFS, the C-indexes of the NWR were 0. 88 and 0.88 in the training set, respectively, while the C-indexes of the NWOR were 0. 82 and 0.85 in the training set, respectively.ConclusionsThe PET/CT-based radiomics analysis might serve as a non-invasive approach to predict LVI status in GC patients and provide effective predictors of patient survival outcomes.

Peripheral Cytokine Levels as a Prognostic Indicator in Gastric Cancer: A Review of Existing Literature.

Although strong connections exist between the carcinogenesis of gastric cancer and chronic inflammation, gastric cancer is unique in that the chronic gastritis which frequently precedes carcinogenesis is strongly associated with H. pylori infection. The interplay between H. pylori virulence factors and host immune cells is complex but culminates in the activation of inflammatory pathways and transcription factors such as NF-κB, STAT3, and AP-1, all of which upregulate cytokine production. Due to the key role of cytokines in modulating the immune response against tumour cells as well as possibly stimulating tumour growth and proliferation, different patterns of cytokine secretion may be associated with varying patient outcomes. In relation to gastric cancer, interleukin-6, 8, 10, 17A, TNF, and IFN-γ may have pro-tumour properties, although interleukin-10, TNF, and IFN-γ may have anti-tumour effects. However, due to the lack of studies investigating patient outcomes, only a link between higher interleukin-6 levels and poorer prognosis has been demonstrated. Further investigations which link peripheral cytokine levels to patient prognosis may elucidate important pathological mechanisms in gastric cancer which adversely impact patient survival and allow treatments targeting these processes to be developed.

Bioinformatic Analysis Identified Potentially Prognostic Long Noncoding RNAs and MicroRNAs for Gastric Cancer.

Gastric cancer (GC) is the fifth most common malignant tumor in the world. The present study was performed to discover the potential diagnostic and therapeutic long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) of GC. Data used in this study to identify differentially expressed lncRNAs (DElncRNAs) and miRNAs (DEmiRNAs) were obtained from 187 GC tissues and 32 adjacent nontumor tissues. The total clinical data on GC included 187 cases. The above data were from the TCGA database. RStudio/Bioconductor software was used to conduct univariate analysis, the least absolute shrinkage and selection operator (LASSO) Cox, and multivariate Cox proportional risk regression for the DElncRNAs and DEmiRNAs. Clinical information was analyzed through univariate and multivariate Cox analysis. Results: five lncRNAs (AC007785.3, AC079385.3, LINC00392, LINC01729, and U95743.1) and two miRNAs (hsa-miR-3174, hsa-miR-605) were proven to be independent prognostic indicators of GC. Results of the Kaplan-Meier survival analysis showed that AC007785.3, AC079385.3, LINC01729, miR-3174, and miR-605 were significantly correlated with OS of GC. The target genes of AC079385.3, miR-3174, and miR-605 were obtained and clustered mainly on MAPK and cGMP-PKG signaling pathways. The clinical data showed that age and clinicopathologic stage were correlated with the prognosis of GC. Furthermore, AC007785.3 was associated with metastasis of GC, and miR-3174 was associated with the primary tumor condition of GC. We identified three lncRNAs (AC007785.3, AC079385.3, LINC01729), two miRNAs (miR-3174, miR-605), and clinical factors related to the pathogenesis and prognosis of GC. Our predicted results provide a possible entry point for the study of prognostic markers for GC.

Significance of a preoperative systemic immune-inflammation index as a predictor of postoperative survival outcomes in gastric cancer

BackgroundSince inflammation and the immune system contribute to the development and progression of malignancies, parameters that reflect a host’s immune-inflammatory status may be useful prognostic indicators of gastric cancer (GC). The present study examined the clinical significance of a preoperative systemic immune-inflammation index (SII) for predicting postoperative survival outcomes in GC.MethodsA total of 447 patients who underwent curative gastrectomy for GC were included in the present study. SII was calculated as platelet count × neutrophil count/lymphocyte count. The prognostic impact of preoperative SII was examined using univariate and multivariate analyses.ResultsPreoperative SII ranged between 105 and 4455 (median 474), and the optimal cutoff value for predicting overall survival (OS) was 395 based on a receiver operating characteristic curve. The 5-year OS rate of the SII ≥ 395 group was 80.0%, which was significantly worse than that (92.7%) of the SII < 395 group (p < 0.001). The multivariate analysis identified SII ≥ 395 (hazard ratio [HR] 2.95; 95% confidence interval [CI] 1.49–6.39; p = 0.001), heart disease (HR 2.14, 95% CI 1.07–4.07), C-reactive protein ≥ 0.5 (HR 2.45, 95% CI 1.15–4.94), pT4 (HR 4.46, 95% CI 2.44–8.14), and pN+ (HR 4.02, 95% CI 2.10–7.93) as independent predictors of worse OS. Peritoneal recurrence was more frequent in the high SII group than in the low SII group (p = 0.028).ConclusionPreoperative SII may be a useful predictor of postoperative survival outcomes in GC. The meticulous surveillance of GC relapse, particularly peritoneal dissemination, is necessary for patients with SII ≥ 395 even after curative gastrectomy.

Circular RNA hsa_circ_0001874 is an indicator for gastric cancer.

BackgroundRecent studies have indicated that circular RNAs (circRNAs) are novel endogenous RNAs whose 5′ and 3′ ends are covalently linked and play critical roles in gastric carcinogenesis. However, the significance of circRNA hsa_circ_0001874 in gastric cancer (GC) is still unclear.MethodsTherefore, we first detected hsa_circ_0001874 levels in GC cell lines and tissues and analyzed their potential correlation with clinicopathological factors. Then, a receiver operating characteristic (ROC) curve was established to evaluate its clinical value. Finally, we further predicted the biological functions of this molecule by bioinformatics analysis.ResultsOur data showed that as an indicator, hsa_circ_0001874 expression was significantly decreased in 78.02% (71/91) of the GC patients. Combined with clinicopathological factors, the hsa_circ_0001874 level was strongly associated with cell differentiation (p < 0.001), tumor stage (p = 0.005), invasion (p = 0.024), lymphatic metastasis (p = 0.023), and CEA level (p < 0.001) in GC tissues. The area under the curve (AUC) was up to 0.673, with a sensitivity and specificity of 61.54% and 68.13%, respectively. Bioinformatics analysis showed that hsa_circ_0001874 harbors miR‐593‐5p, miR‐103a‐3p, and miR‐107 seed sequences to regulate these three miRNAs and downstream target genes and exert its various biological functions in the carcinogenesis and progression of GC.ConclusionIn summary, these data suggest that hsa_circ_0001874 is an indicator of GC and plays a significant role in gastric carcinogenesis and progression.

GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in gastric cancer

It is vital to identify effective therapeutic targets and explore the underlying mechanisms to curb the progression of Gastric cancer (GC) and improve the prognosis of GC patients. Guanine-rich RNA sequence binding factor 1 (GRSF1) is a member of the RNA-binding protein family. The present study showed that GRSF1 knockdown suppressed GC cells proliferation, migration and invasion in vitro, while GRSF1 overexpression enhanced the proliferation, migration and invasion of GC cells. Meanwhile, knockdown of GRSF1 inhibited tumor growth and tumor metastasis in vivo. Furthermore, we demonstrated that GRSF1 induced epithelial-mesenchymal transition (EMT) and activated PI3K/AKT pathway in vitro and in vivo through gain and loss of function. In conclusion, we demonstrated that GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in GC. Our study for the first time identified the functions of GRSF1 serving as an oncogene in GC, which may be a potential effective therapeutic target and malignant indicator in GC.

Serum CD4 Is Associated with the Infiltration of CD4+T Cells in the Tumor Microenvironment of Gastric Cancer.

Serum CD4, CD8, and CD19 are markers of systemic inflammation. However, there is little evidence on the influence of inflammation on the tumor microenvironment and the prognostic indicators of gastric cancer (GC). In this study, two hundred and eight patients who underwent radical gastrectomy for GC were included. Preoperative peripheral blood samples were used to analyze Serum CD4, CD8, and CD19. The optimal cutoff levels for CD4, CD8, and CD19 were defined by receiver operating characteristic curve analysis (CD4 = 38.85%, CD8 = 14.35%, and CD19 = 7.40%). The areas with specific CD4+T cells, CD8+T cells, and CD19+B cells within the tumor microenvironment were measured in paraffin sections by immunohistochemistry and analyzed by Image-Pro Plus. 94 patients had low CD4, and 124 patients had high CD4 levels. 31 patients had low CD8, and 187 patients had high CD8 levels. 64 patients had low CD19, and 154 patients had high CD19 levels. Infiltration of CD4+T cells was associated with serum CD4 (P < 0.001). Serum CD4 and CD19 and the infiltration of CD4+T cells, CD8+T cells, and CD19+B cells were significant in predicting the prognosis of GC. Low CD4 level, infiltration of CD8+T cells, and high infiltration of CD4+T cells and CD19+B cells were correlated with worse overall survival in multivariate analysis. Collectively, our results provide evidence that serum CD4 is associated with the infiltration of CD4+T cells in the tumor microenvironment, which indicates the prognostic value of systemic inflammation in GC.

S3305 Surgical Outcomes of Gastric Cancer Patients Seen at a Safety Net Hospital in an Urban Academic Setting

INTRODUCTION: Gastric cancer remains a significant public health concern, and it is the third leading cause of cancer related deaths worldwide. We evaluated surgical outcomes in gastric cancer patients seen at a safety-net hospital with a high immigrant patient population. METHODS: A retrospective study was conducted to identify patients diagnosed with gastric cancer between 2010 and 2019 (N = 111) at our institution. All cases were histologically confirmed. Data on demographics, pathology, type of gastric cancer, surgery, and chemotherapy were obtained. Kaplan Meier and Cox regression analyses were used to evaluate factors associated with survival. Hazard ratios (HR) and confidence intervals (CI) are reported. RESULTS: Of the 111 patients with gastric cancer included in this study, 41.2% of patients underwent surgery; of which 26.2% were proximal, 52.4% were distal, and 21.4% were total gastrectomies (Table 1). Also, 61.9% of the surgeries were radical, and 38.1% palliative. Likewise, 68.4% had chemotherapy, of which 27.3% was neoadjuvant, 9.1% was adjuvant, and 63.6% was palliative. Gastric adenocarcinoma types were diffuse-type (61%), intestinal-type (33%), and mixed-type (6%). Diffuse-type cancer was more common in the younger population (≤40 years) compared to the older population, >40 years (P = 0.01). Mortality was significantly lower in those who had surgery (HR 0.36 CI 0.18–0.78), chemotherapy (HR 0.43 CI 0.23–0.80) compared to those who did not (P < 0.001). furthermore, patients who had neoadjuvant chemotherapy had a lower mortality compared to those who received palliative chemotherapy (HR 0.37 CI 0.15–0.89). Although survival appeared to be higher in patients with intestinal-type cancer compared to those with diffuse-type cancer who underwent surgery, this difference was not statistically significant (P = 0.136) See Figure 1. CONCLUSION: Gastric cancer surgery was associated with a lower mortality in our patient population. Also, multimodal therapy including surgery, chemotherapy, and neoadjuvant chemotherapy all improved survival outcomes. There was no difference in survival between patients with intestinal-type cancer compared to those with diffuse-type cancer who underwent surgery. In addition, the fact that diffuse-type cancer was more common in the younger population suggest that genetics may play a major role in these gastric cancer subtype. Further research is needed to identify pertinent prognostic indicators in gastric cancer patients.Figure 1Table 1.: Gastric cancer percentages for surgery and chemotherapy

Upregulation of ECT2 is associated with transcriptional program of cancer stem cells and predicts poor clinical outcome in gastric cancer.

Gastric cancer remains the third leading cause of cancer-associated mortality worldwide. The identification of prognostic indicators that are associated with clinical characteristics is urgently required. The aim of the present study was to determine the involvement of epithelial cell transforming 2 (ECT2) in gastric cancer. The results of the present study demonstrated that ECT2 expression was upregulated in human gastric cancer samples. Furthermore, high ECT2 expression was associated with advanced Tumor-Node-Metastasis stage and deeper tumor invasion. ECT2 upregulation was further confirmed in several independent publicly available clinical cohorts from the Gene Expression Omnibus database. In addition, patients with gastric cancer, with high ECT2 expression exhibited a significantly shorter overall survival time than those with low ECT2 expression, and Cox regression analysis demonstrated that ECT2 expression was an independent prognostic marker for overall survival time. Characterization of the transcriptome profiles of ECT2 upregulated gastric tumors indicated that ECT2 upregulation may be associated with transcriptional features of cancer stem cells (CSCs). Additionally, BUB1 mitotic checkpoint serine/threonine kinase and E2F transcription factor 7, two genes previously reported to account for the functionality of CSCs, were strongly enriched in ECT2High gastric cancer samples. Taken together, the results of the present study suggest that ECT2 may serve as a novel marker for CSCs and may be a potential prognostic indicator in gastric cancer.

Investigation of the association between C-X-C motif chemokine receptor subunits and tumor infiltration levels and prognosis in patients with early-stage pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the malignancies with the highest morality rate due to postoperative local invasion and distant metastasis. Although C-X-C motif chemokine receptor (CXCR) subunits have been reported as prognostic indicators in gastric cancer, the prognostic value of CXCR subunits in PDAC remains poorly understood. In the present study, the expression levels and biological functions of CXCR subunits were investigated using multiple publicly accessible bioinformatic platforms and databases. Survival analysis was used to evaluate the prognostic value of CXCR subunits in 112 early-stage PDAC cases by setting the median expression levels as the cut-off values. A nomogram was constructed to combine CXCR subunit expression levels and clinical data for prognosis prediction. Moreover, the association between CXCR subunit expression levels and tumor infiltration levels were detected in PDAC. The expression levels of CXCR subunits were elevated in PDAC tumor tissues. In the multivariate Cox proportional risk regression model, high CXCR2, CXCR4 and CXCR6 expression levels in early-stage PDAC were associated with a more favorable prognosis. Further, it was demonstrated that the differential expression levels of CXCR subunits in PDAC for combined survival analysis could contribute to risk stratification. The nomogram model demonstrated the contribution of CXCR subunits and clinical features in the prognosis of PDAC. Gene Set Enrichment Analysis suggested that CXCR subunits serve a role in immunomodulatory functions. The expression levels and somatic copy number alterations of CXCR subunits were associated with tumor infiltration levels in PDAC. CXCR subunits were associated with prognosis in patients with early-stage PDAC and may be potential drug targets for the treatment of pancreatic cancer.

RETRACTED ARTICLE: The novel long non-coding RNA LATS2-AS1-001 inhibits gastric cancer progression by regulating the LATS2/YAP1 signaling pathway via binding to EZH2

BackgroundTo explore the expression pattern and role of the novel long non-coding RNA LATS2 antisense transcript 1 (LATS2-AS1-001) in gastric cancer (GC).MethodsqRT-PCR was applied to evaluate LATS2-AS1-001 expression and correlation with LATS2 in GC. In vitro experiments were performed to investigate the role of LATS2-AS1-001 in GC cells. RNA immunoprecipitation (RIP) was performed to assess the interaction between EZH2 and LATS2-AS1-001. LATS2/YAP1 signaling pathway proteins were detected by immunoblot. Oncomine and KMPLOT data analysis was conducted to assess the prognostic value of YAP1 in GC.ResultsDecreased expression levels of LATS2-AS1-001 and LATS2 were confirmed in 357 GC tissues compared with the normal mucosa. A strong positive correlation between LATS2-AS1-001 and LATS mRNA expression was found in Pearson Correlation analysis (r = 0.719, P < 0.001). Furthermore, ROC curve analysis revealed areas under the curves for LATS2-AS1-001 and LATS2 of 0.7274 and 0.6865, respectively (P < 0.001), which indicated that LATS2-AS1-001 and LATS could be used as diagnostic indicators in GC. Moreover, ectopic expression of LATS2-AS1-001 decreased cell viability, induced G0/G1 phase arrest, and inhibited cell migration and invasion in GC cells. Mechanistically, overexpressing LATS2-AS1-001 upregulated LATS2 and induced YAP1 phosphorylation via binding to EZH2. Oncomine and KMPLOT database analysis demonstrated YAP1 was highly expressed in human GC samples, and high YAP1 expression predicted poor patient prognosis in GC.ConclusionThis study revealed that lncRNA LATS2-AS1-001 might serve as a potential diagnostic index in GC and act as a suppressor of GC progression.

P2X7 receptor as an independent prognostic indicator in gastric cancer.

Gastric cancer (GC) is one of the foremost causes of cancer-related death around the world. The P2X7 receptor (P2X7R), a member of the P2X7R subfamily of P2 receptors, is a unique molecule that has been shown to affect tumor growth and progression as well as various inflammatory processes, including proliferation of T lymphocytes, release of cytokines, and production of free oxygen radicals. P2X7R has been established as a prognostic parameter in some cancers, and recently, it has been investigated in the development of new targeted therapies. In the present study, we aimed to investigate the prognostic value of P2X7R expression in GC. The expression profile of P2X7R was evaluated immunohistochemically in 156 paraffin-embedded human GC specimens. P2X7R expression was higher in patients with lymph node metastasis than in those without (p < 0.001). P2X7R overexpression was closely related with tumor-infiltrating lymphocytes (TILs) (p = 0.001), vascular invasion (p = 0.006), depth of invasion (p < 0.001), distant metastasis (p < 0.001), and advanced tumor, node, metastasis stage (p < 0.001). Moreover, univariate (hazard ratio [HR] 3.98; 95% confidence interval (CI) 1.89-11.82; p < 0.001) and multivariate (HR 2.24; 95% CI 3.53-12.50; p < 0.001) Cox regression analysis showed that upregulated P2X7R expression clearly correlated with worsened overall survival. In summary, our data revealed that P2X7R may serve as a reliable prognostic parameter and promising therapeutic target for GC.

Distinct expression and prognostic values of the replication protein A family in gastric cancer.

The replication protein A (RPA)1-4 family are single-stranded DNA-binding proteins that are essential components of DNA replication, repair and recombination, and cell cycle regulation. The present study aimed to evaluate the prognostic value of the RPA family members in patients with gastric cancer (GC), using datasets retrieved from the Oncomine public database. Datasets were retrieved for the purpose of comparing the RPA expression levels between GC and normal tissues. Additionally, Kaplan-Meier analysis was used to compare the overall survival (OS) times of GC patients that expressed different levels of RPA proteins. RPA1, 2, and 3 expression levels were all significantly upregulated in gastric intestinal-type, diffuse gastric, and gastric mixed adenocarcinomas, compared with those in normal mucosal tissues. Moreover, high mRNA expression levels of RPA3 and 4 predicted poorer OS times in all GCs, as well as patients with human epidermal growth factor receptor 2-negative and -positive GC. The high-risk group, separated by RPA signature, showed a poorer outcome than the low-risk group. RPA3 was the most strongly correlated with CD4+ T-cell levels. In conclusion, RPAs are novel prognostic indicators in GC, and can also predict the features of immunological diseases. Future experimental investigation into the roles of RPAs concerning the pathogenesis and development of GC may provide a novel biomarker or therapeutic target, improving the prognosis of patients with GC.