Prognostic Factor In Gastric Cancer Research Articles

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.

Over-expression of Anterior Gradient 3 Is Associated With Tumor Progression and Poor Survival in Gastric Cancer.

Anterior gradient (AGR) proteins, including AGR1, AGR2, and AGR3, which are members of the protein disulfide isomerase family, have been reported as biomarkers for various carcinogenesis processes. Although AGR2 and AGR1 have been demonstrated to be associated with gastric cancer (GC) progression and poor survival, the effect of AGR3 on the progression and prognosis of GC remains unknown. Therefore, our study aimed to examine the expression and prognostic significance of AGR3 in patients with GC. We investigated 271 GC patients receiving curative surgery. Formalin-fixed and paraffin-embedded tissue blocks were obtained, and long-term survival analysis was performed. The expression of AGR3 in GC tissues was investigated by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. AGR3 was over-expressed in GC tissue compared with paired normal tissue at the mRNA and protein levels. AGR3 over-expression was significantly associated with larger tumor size, deeper tumor invasion, lymph node metastasis, and advanced tumor stage. The overall survival of patients with positive AGR3 expression was significantly lower than that of patients without positive AGR3 expression. Multivariate analysis demonstrated that AGR3 and age were independent prognostic factors associated with overall survival. Over-expression of AGR3 was significantly associated with tumor progression and poor survival of GC patients. Therefore, AGR3 may be a novel biomarker and prognostic factor for GC.

Clinical value of regional lymph node sorting in gastric cancer.

Increasing evidence have shown that regional lymph node metastasis is a critical prognostic factor in gastric cancer (GC). In addition, lymph node dissection is a key factor in determining the appropriate treatment for GC. However, the association between the number of positive lymph nodes and area of lymph node metastasis in GC remains unclear. To investigate the clinical value of regional lymph node sorting after radical gastrectomy for GC. This study included 661 patients with GC who underwent radical gastrectomy at Tianjin Medical University General Hospital between January 2012 and June 2020. The patients were divided into regional sorting and non-sorting groups. Clinicopathological data were collected and retrospectively reviewed to determine the differences in the total number of lymph nodes and number of positive lymph nodes between the groups. Independent sample t-tests were used for intergroup comparisons. Continuous variables that did not conform to a normal distribution were expressed as median (interquartile range), and the Mann-Whitney U test was used for inter-group comparisons. There were no significant differences between the groups in terms of the surgical method, tumor site, immersion depth, and degree of differentiation. The total number of lymph nodes was significantly higher in the regional sorting group (n = 324) than in the non-sorting group (n = 337) (32.5 vs 21.2, P < 0.001). There was no significant difference in the number of positive lymph nodes between the two groups. A total of 212 patients with GC had lymph node metastasis in the lymph node regional sorting group, including 89 (41.98%) cases in the first dissection station and 123 (58.02 %) cases in the second dissection station. Binary and multivariate logistic regression results showed that the number of positive lymph nodes (P < 0.001) was an independent risk factor for lymph node metastases at the second dissection station. Regional sorting of lymph nodes after radical gastrectomy may increase the number of detected lymph nodes, thereby improving the reliability and accuracy of lymph node staging in clinical practice.

DUSP5P1 promotes gastric cancer metastasis and platinum drug resistance

We elucidated the functional significance and molecular mechanisms of DUSP5P1 lncRNA (dual specificity phosphatase 5 pseudogene 1) in gastric carcinogenesis. We demonstrated that gastric cancer (GC) patients with high DUSP5P1 expression had shortened survival in two independent cohorts. DUSP5P1 promoted GC cell migration and invasion in vitro and metastasis in vivo. Mechanistically, DUSP5P1 activated ARHGAP5 transcription by directly binding to the promoter of ARHGAP5 with a binding motif of TATGTG. RNA-seq revealed that ARHGAP5 activated focal adhesion and MAPK signaling pathways to promote GC metastasis. DUSP5P1 also dysregulated platinum drug resistance pathway. Consistently, DUSP5P1 overexpression in GC cells antagonized cytotoxic effect of Oxaliplatin, and shDUSP5P1 plus Oxaliplatin exerted synergistic effect on inhibiting GC metastasis in vitro and in vivo. DUSP5P1 depletion also suppressed the growth of platinum drug-resistant PDO models. In conclusion, DUSP5P1 promoted GC metastasis by directly modulating ARHGAP5 expression to activate focal adhesion and MAPK pathways, serves as therapeutic target for platinum drug resistant GC, and is an independent prognostic factor in GC.

High Frequency of Microsatellite Instability among Non-Metastatic Gastric Cancer.

Background: Microsatellite instability (MSI) is considered a key factor in carcinogenesis and a genetic alteration pattern in many types of cancers such as gastric cancer (GC). Although the role of MSI in colorectal cancer (CRC) is well known, its prognostic impact on GC has not been clearly defined. The assessment of MSI in GC has notbeen documented in the Iranian population yet. Therefore, this study analyzed the association of MSI status with GC in Iranian patients. Materials and Methods: We compared the frequency of MSI at 5 loci from formalin-fixed paraffin-embedded (FFPE) gastrectomy specimens, between metastatic and non-metastatic cases of GC (N = 60). A panel of five quasi-monomorphic markers and a single dinucleotide marker with linker-based fluorescent primers was used. Results: MSI was observed in 46.6% of cases, including MSI-high (H) (33.3%) and MSI-Low (L) (13.3%). Moreover, the most unstable and stable markers in our study were NR-21 and BAT-26 accordingly. MSI-H and MSI were seen more frequently in non-metastatic tumors (p= 0.028 and p= 0.019, respectively). Conclusion: The current study showed MSI status more frequently in non-metastatic GC which may reflect a good prognostic factor in GC like CRC. Although, larger and more comprehensive studies are needed to confirm this statement. A panel consisting of NR-21, BAT-25, and NR-27 mononucleotide markers appears to be reliable and useful markers for detecting MSI in GC in Iranian patients.

Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer.

Background: Gastric cancer remains the most prevalent and highly lethal disease worldwide. MAP4K4, a member of Ste20, plays an important role in various pathologies, including cancer. However, its role in gastric cancer is not yet fully elucidated. Therefore, this study aims to determine the tumor-promoting role of MAP4K4 in gastric cancer and whether it can be used as a new and reliable biomarker to predict the prognosis of gastric cancer. For this purpose, we divide the samples into high- and low-expression groups according to the expression level of MAP4K4. The association of MAP4K4 expression with prognosis is assessed using the Kaplan–Meier survival analysis. Furthermore, immune infiltration analysis using ESTIMATE is conducted to evaluate the tumor immune scores of the samples. Results: The findings reveal a significantly higher expression of MAP4K4 in tumor samples than in adjacent samples. The high-expression group was significantly enriched in tumor-related pathways, such as the PI3K-Akt signaling pathway. In addition, immune infiltration analysis revealed a positive correlation between immune scores and MAP4K4 expression. We also observed that miRNAs, such as miR-192-3p (R = −0.317, p-value 3.111 × 10−9), miR-33b-5p (R= −0.238, p-value 1.166 × 10−5), and miR-582-3p (R = −0.214, p-value 8.430 × 10−5), had potential negative regulatory effects on MAP4K4. Moreover, we identified several transcription factors, ubiquitinated proteins, and interacting proteins that might regulate MAP4K4. The relationship between MAP4K4 and DNA methylation was also identified. Finally, we verified the high expression of MAP4K4 and its effect on promoting cancer. Conclusion: MAP4K4 might be closely related to gastric cancer’s progression, invasion, and metastasis. Its high expression negatively impacts the prognosis of gastric cancer patients. This suggests MAP4K4 as an important prognostic factor for gastric cancer and could be regarded as a new potential prognostic detection and therapeutic target.

A multi-task deep learning framework for perineural invasion recognition in gastric cancer whole slide images

Perineural invasion (PNI) is the process of neoplastic invasion of the nerves and is a prognostic factor in gastric cancer. However, such examination is a labor-intensive task in high-resolution digital pathological images. To alleviate this problem, we propose a multi-task deep learning-based framework to highlight diagnostically significant PNI regions in whole slide images (WSIs) of human gastric cancer tissue sections. The proposed framework includes a gastric cancer segmentation model, neural detection model, and PNI decision-making module, which realizes the segmentation of the gastric cancer region while completing the task of identifying PNI. Adequate comparative experiments were performed on our own gastric cancer PNI dataset called GC-PNI. Experiments have shown that our proposed model can effectively diagnose PNI with a high sensitivity of 0.972 and a specificity of 0.933, illustrating the potential of this practical application.