Survival Time Of Gastric Cancer Patients Research Articles

Screening of differentially expressed genes in gastric cancer based on GEO database and function and pathway enrichment analysis

To explore the core genes related to the diagnosis and prognosis of gastric cancer (GC) based on Gene Expression Omnibus (GEO) database and screen the molecular targets involved in the occurrence and development of GC. GC microarray data GSE118916, GSE54129 and GSE79973 were downloaded from GEO database, and the differentially expressed genes (DEGs) were screened. Enrichment analysis of the signaling pathways and molecular functions were preformed and protein-protein interaction networks (PPI) were constructed to identify the hub genes, whose expression levels and diagnostic and prognostic values were verifies based on gastric adenocarcinoma data from TCGA. The expression levels of these core genes were also detected in different GC cell lines using qRT- PCR. Seventy-seven DEGs were identified, which encodes proteins located mainly in the extracellular matrix and basement membrane with activities of oxidoreductase and extracellular matrix receptor and ligand, involving the biological processes of digestion and hormone metabolism and the signaling pathways in retinol metabolism and gastric acid secretion. Nine hub genes were obtained, among which SPARC, TIMP1, THBS2, COL6A3 and THY1 were significantly up- regulated and TFF1, GKN1, TFF2 and PGC were significantly down-regulated in GC. The abnormal expressions of SPARC, TIMP1, THBS2, COL6A3, TFF2 and THY1 were significantly correlated with the survival time of GC patients. ROC curve analysis showed that aberrant expression of TIMP1 SPARC, THY1 and THBS2 had high diagnostic value for GC. High expressions of SPARC, TIMP1, THBS2 and COL6A3 were detected in GC tissues. In the GC cell lines, qRT- PCR revealed different expression patterns of these hub genes, but their expressions were largely consistent with those found in bioinformatics analyses. SPARC, TIMP1, THBS2 and other DEGs are probably involved in GC occurrence and progression and may serve as potential candidate molecular markers for early diagnosis and prognostic evaluation of GC.

Changing trends in gastric and colorectal cancer among surgical patients over 85 years old: A multicenter retrospective study, 2001-2021.

Whether patients over 85 years old with gastrointestinal cancer should undergo surgery remains controversial. We aimed to describe the changing trends of characteristics to provide more information to decision makers, and strive to find appropriate surgical plan. To describe the changing trends of characteristics to provide more information to decision makers, and strive to find appropriate surgical plan. A total of 218 gastric cancer (GC) patients and 563 colorectal cancer (CRC) patients who underwent surgery between 2001 and 2021 were enrolled in this retrospective analysis. Changes in clinicopathological features, surgical treatments, and survival status were analyzed longitudinally at 5-year intervals. Only 14 GC patients underwent laparoscopic surgery where 219 CRC patients had this procedure. Cardia and esophagogastric junction cancer increased in GC patients, and the proportion of sigmoid colon cancer decreased in CRC patients. Pulmonary infection gradually became the most common postoperative complication, its incidence in period 4 reached 48.79%. However, the incidence of anastomotic leakage decreased from 26.79% to 9.38% (P < 0.01). Additionally, 30-d mortality significantly decreased from 32.14% to 9.01%. Increases were observed in 5-year overall survival (OS) in GC patients from period 1 to period 4 (18.18% vs 33.32%, respectively) and CRC patients (0 vs 36.32%, respectively). Disease-free survival (DFS) also increased in GC and CRC patients (7.14% vs 27.74% and 0 to 36.03%, respectively). The average survival time of GC patients following radial lymphadenectomy was higher than in patients that underwent limited lymphadenectomy (26 vs 22 mo, respectively), the same was seen in CRC patients (44 vs 33 mo, respectively). This advantage was particularly evident in patients with TNM I, but not in patients with TNM II/III period cancer. The safety as well as effectiveness of surgery in ultra-elderly patients is increasing. Radical lymphadenectomy has advantages in patients with TNM I gastrointestinal cancer, but not TNM II/III.

A comprehensive evaluation of serum tRF-29-R9J8909NF5JP as a novel diagnostic and prognostic biomarker for gastric cancer.

Gastric cancer (GC) is a common malignant digestive system tumor. Since the early symptoms of GC are usually vague and the positive rate of common biomarkers of GC is low, it is of urgent need to find new biomarkers with good sensitivity and specificity to screen and diagnose GC patients. The tRNA-derived small RNAs (tsRNAs) are emerging small noncoding RNAs that play an essential role in cancer progression. In this study, we explored whether novel tsRNAs have the potential to serve as biomarkers for GC. Three tsRNAs significantly upregulated in GC were screened by the tsRFun database. The expression level of tRF-29-R9J8909NF5JP was detected by real-time fluorescence quantitative polymerase chain reaction. Agarose gel electrophoresis and Sanger sequencing were used to verify the characteristics of tRF-29-R9J8909NF5JP. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of tRF-29-R9J8909NF5JP. The χ2 test was used to analyze the correlation between tRF-29-R9J8909NF5JP expression level and clinicopathological parameters. Kaplan-Meier survival curves were used to analyze the correlation between tRF-29-R9J8909NF5JP expression levels and survival time of GC patients. In this study, the expression level of tRF-29-R9J8909NF5JP was significantly increased in GC tissues. The expression level of tRF-29-R9J8909NF5JP was considerably higher in the serum of GC patients than in the serum of gastritis patients and in the serum of healthy donors, and the expression level of tRF-29-R9J8909NF5JP was significantly decreased in the serum of GC patients after surgery. In addition, the χ2 test showed that the expression level of tRF-29-R9J8909NF5JP in GC serum was correlated with differentiation grade, T-stage, lymph node metastasis, tumor node metastasis stage, and neurological/vascular invasion. The results of the survival curve showed that the high expression of serum tRF-29-R9J8909NF5JP was associated with a low survival rate. ROC analysis showed that serum tRF-29-R9J8909NF5JP had higher diagnostic efficiency than common GC biomarkers, and the diagnostic efficiency was further improved by combining them. At the end of the study, we predicted the downstream of tRF-29-R9J8909NF5JP. The expression level of tRF-29-R9J8909NF5JP in the serum of GC patients can effectively identify GC patients and has higher efficacy than conventional biomarkers. In addition, serum tRF-29-R9J8909NF5JP can monitor the postoperative condition of GC patients, suggesting that it has the potential to become a biomarker for GC.

Novel m7G-related lncRNA signature for predicting overall survival in patients with gastric cancer

Presenting with a poor prognosis, gastric cancer (GC) remains one of the leading causes of disease and death worldwide. Long non-coding RNAs (lncRNAs) regulate tumor formation and have been long used to predict tumor prognosis. N7-methylguanosine (m7G) is the most prevalent RNA modification. m7G-lncRNAs regulate GC onset and progression, but their precise mechanism in GC is unclear. The objective of this research was the development of a new m7G-related lncRNA signature as a biomarker for predicting GC survival rate and guiding treatment. The Cancer Genome Atlas database helped extract gene expression data and clinical information for GC. Pearson correlation analysis helped point out m7G-related lncRNAs. Univariate Cox analysis helped in identifying m7G-related lncRNA with predictive capability. The Lasso-Cox method helped point out seven lncRNAs for the purpose of establishing an m7G-related lncRNA prognostic signature (m7G-LPS), followed by the construction of a nomogram. Kaplan–Meier analysis, univariate and multivariate Cox regression analysis, calibration plot of the nomogram model, receiver operating characteristic curve and principal component analysis were utilized for the verification of the risk model’s reliability. Furthermore, q-PCR helped verify the lncRNAs expression of m7G-LPS in-vitro. The study subjects were classified into high and low-risk groups based on the median value of the risk score. Gene enrichment analysis confirmed the constructed m7G-LPS’ correlation with RNA transcription and translation and multiple immune-related pathways. Analysis of the clinicopathological features revealed more progressive features in the high-risk group. CIBERSORT analysis showed the involvement of m7G-LPS in immune cell infiltration. The risk score was correlated with immune checkpoint gene expression, immune cell and immune function score, immune cell infiltration, and chemotherapy drug sensitivity. Therefore, our study shows that m7G-LPS constructed using seven m7G-related lncRNAs can predict the survival time of GC patients and guide chemotherapy and immunotherapy regimens as biomarker.

Inhibition of androgen receptor enhanced the anticancer effects of everolimus through targeting glucose transporter 12.

Everolimus was designed as a mammalian target of rapamycin (mTOR) inhibitor. It has been proven as a targeted drug for gastric cancer (GC) therapy. However, long-term treatment with everolimus may cause severe side effects for recipients. Decreasing the dosage and attenuating the associated risks are feasible to promote clinical translation of everolimus. This study aimed to identify the underlying mechanisms of responses to everolimus and develop novel regimens for GC treatment. Our findings proved that there was a significant dose-dependent relationship of everolimus-induced GC cell apoptosis and glycolysis inhibition. Then, we found that a member of glucose transporter (GLUT12) family, GLUT12, was actively upregulated to counteract the anticancer effects of everolimus. GLUT12 might be overexpressed in GC. High expression of GLUT12 might be correlated with tumor progression and short survival time of GC patients. Bioinformatic analysis suggested that GLUT12 might be involved in regulating cancer development and metabolism. The experiments proved that GLUT12 significantly promoted GC growth, glycolysis and impaired the anticancer effects of everolimus. Androgen receptor (AR) is a classical oncogenic factor in many types of cancer. Everolimus elevated GLUT12 expression in an AR-dependent manner. Inhibition of AR activity abrogated the promotive effects on GLUT12 expression. Both in-vitro and in-vivo experiments demonstrated that GLUT12 knockdown augmented anticancer effects of everolimus. Enzalutamide, an AR inhibitor, or AR knockdown was comparable to GLUT12 suppression. This study identified the role of the AR/GLUT12 pathway in the development of poor responses to everolimus. Interference with AR/GLUT12 pathway may serve as a promising approach to promoting the translational application of everolimus in GC therapy.

The phosphorylation level of Cofilin-1 is related to the pathological subtypes of gastric cancer.

The purpose of the study was to explore the relationship between multiple proteins belonging to the LIMK/Cofilin pathway, including LIMK1, LIMK2, Cofilin-1, and p-Cofilin-1 and clinical features of gastric cancer (GC) patients, including overall survival, TNM stages, and pathological subtypes. The expression of LIMK1, LIMK2, Cofilin-1 and p-Cofilin-1 in the GC tissues and adjacent normal stomach tissues from 141 patients were detected using immunohistochemistry (IHC) staining. Wilcoxon rank-sum test and Spearman rank correlation coefficients were used to measure the relationship between different TNM stages, pathological types, and selected parameters. OS was estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test. Our results showed that, compared to those in the adjacent normal stomach tissues, LIMK1, LIMK2 and Cofilin-1 were up-regulated while p-Cofilin-1 was down-regulated in the GC tissues. LIMK1 level was positively correlated to the TNM stages of GC. According to the published dataset, the expression levels of both LIMK1 and LIMK2 were correlated to the overall survival time of GC patients. The level of Cofilin-1 was significantly different between GCs of different TNM stages. Moreover, most importantly, this is the first study to reveal that the level of Cofilin-1 is higher, and the level of p-Cofilin-1 is lower in the diffuse type of GC compared to that in intestinal type. Taken together, our study demonstrated that multiple factors in LIMK/Cofilin pathway including LIMK1, LIMK2, Cofilin-1, and p-Cofilin-1 were associated with the clinical and pathological features of GC, which is potentially helpful for the diagnosis and treatment of GC.

CircDNMT1 Promotes Malignant Progression of Gastric Cancer Through Targeting miR-576-3p/Hypoxia Inducible Factor-1 Alpha Axis.

BackgroundCircular RNAs (circRNAs) regulate multiple malignant behaviors of various types of cancer. The role of circDNMT1, a newly identified circRNA, remains unknown in gastric cancer (GC). This study aimed to elucidate the underlying mechanisms of circDNMT1 in regulating GC progression.MethodsmicroRNA (miRNA) and circRNA expression was detected by quantitative real-time PCR. Western blotting was performed to measure hypoxia inducible factor-1 alpha (HIF-1α) protein expression. Sanger sequencing, gel electrophoresis and fluorescence in situ hybridization were performed to identify the presence of circDNMT1. The clinicopathological features and overall survival of patients were analyzed based on circDNMT1 expression. The proliferation, migration and invasion of GC cells were determined by cell counting kit-8, 5-ethynyl-2’-deoxyuridine, wound healing and transwell assays. Glycolysis of GC cells was detected based on the levels of glucose uptake, the lactate acid, ATP and pyruvic acid production and the extracellular acidification and oxygen consumption rates. The binding sites between miR-576-3p and circDNMT1 or HIF-1α were predicted by online bioinformatic tools and were validated using RNA pull-down and luciferase reporter assays. Xenograft models were established to determine the effects of the circDNMT1/miR-576-3p/HIF-1α axis on GC growth and metastasis in vivo.ResultscircDNMT1 was successfully identified and shown to be overexpressed in GC tissues and cell lines. The expression levels of circDNMT1 were correlated with pathological T stage, pathological TNM stage and shorter survival time of GC patients. circDNMT1 knockdown inhibited the proliferation, migration, invasion and glycolysis of GC cells. circDNMT1 functioned as an oncogenic factor by sponging miR-576-3p. HIF-1α was negatively regulated by miR-576-3p via binding its mRNA 3’ untranslated region. circDNMT1 promoted malignant behaviors and metabolic reprogramming of GC by targeting the miR-576-3p/HIF-1α axis both in vitro and in vivo.ConclusionThese findings demonstrated that circDNMT1 knockdown inhibited GC proliferation, migration, invasion and glycolysis through sponging miR-576-3p/HIF-1α axis. circDNMT1 may be a novel target for GC treatment.

Circular RNA circ_0006089 regulates the IGF1R expression by targeting miR-143-3p to promote gastric cancer proliferation, migration and invasion

ABSTRACT Circular RNAs (circRNAs) figure prominently in regulating the progression of a variety of human malignancies. This study was performed to probe how circ_0006089 functioned in gastric cancer (GC). CircRNA expression profile GSE83521 was downloaded from Gene Expression Omnibus (GEO) database, and circRNAs and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure circ_0006089, microRNA-143-3p (miR-143-3p) and insulin-like growth factor 1 receptor (IGF1R) mRNA expressions in GC tissues and cell lines. Kaplan-Meier curves were used to detect the relationship between circ_0006089 expression and overall survival time of GC patients. Cell counting kit-8 (CCK-8) and 5-bromo-2-deoxyuridine (BrdU) assays were employed to detect the proliferative ability of GC cells after circ_0006089 was overexpressed or knocked down. Wound healing assay and Transwell assay were executed to examine the migration and invasion ability of GC cells. Western blot was adopted to detect IGF1R protein expressions. Circ_0006089 expression was up-regulated in GC samples and cell lines. And high circ_0006089 expression was associated with shorter survival time in GC patients. Circ_0006089 overexpression in GC cells significantly accelerated GC cell proliferation, migration and invasion, whereas circ_0006089 knockdown resulted in the opposite effects. Additionally, miR-143-3p was validated as a downstream target of circ_0006089, and circ_0006089 could positively regulate IGF1R expression via repressing miR-143-3p. Circ_0006089 is highly expressed in GC, and it promotes the malignancy of GC cells via modulating miR-143-3p/IGF1R axis, suggesting that circ_0006089 may serve as a promising therapeutic target for GC.

Identification of 14 Differentially-Expressed Metabolism-Related Genes as Potential Targets of Gastric Cancer by Integrated Proteomics and Transcriptomics.

Although research on the metabolism related to gastric cancer (GC) is gradually gaining increasing interest, there are few studies regarding metabolism-related genes in GC. Understanding the characteristic changes of metabolism-related genes at the transcriptional and protein levels in GC will help us to identify new biomarkers and novel therapeutic targets. We harvested six pairs of samples from GC patients and evaluated the differentially expressed proteins using mass spectrometry-based proteomics. RNA sequencing was conducted simultaneously to detect the corresponding expression of mRNAs, and bioinformatics analysis was used to reveal the correlation of significant differentially expressed genes. A total of 57 genes were observed to be dysregulated both in proteomics and transcriptomics. Bioinformatics analysis showed that these differentially expressed genes were significantly associated with regulating metabolic activity. Further, 14 metabolic genes were identified as potential targets for GC patients and were related to immune cell infiltration. Moreover, we found that dysregulation of branched-chain amino acid transaminase 2 (BCAT2), one of the 14 differentially expressed metabolism-related genes, was associated with the overall survival time in GC patients. We believe that this study provides comprehensive information to better understand the mechanism underlying the progression of GC metastasis and explores the potential therapeutic and prognostic metabolism-related targets for GC.

Positive H. pylori status predicts better prognosis of non-cardiac gastric cancer patients: results from cohort study and meta-analysis

BackgroundPrevious researches have associated Helicobacter pylori (H. pylori) with a prognosis of gastric cancer (GC), however, without a concert conclusion. This study aimed to study this issue further by a prospective cohort study and a meta-analysis.MethodsHistologically diagnosed gastric cancer (GC) patients were recruited into the primary prospective cohort study between January 2009 to December 2013. All the patients were followed-up periodically to record information on post-surgery therapy and overall survival status. The pre-surgery status of H. pylori was measured by enzyme-linked immunosorbent assay. A meta-analysis was conducted after retrieving related researches in the databases of PubMed and Embase up to April 2020. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were summarized to validate the relationship between H. pylori infection and the survival time of GC patients. I2 statistics and Q test were used to assess the heterogeneity. Sensitivity analyses were performed using Galbraith’s plot, leave-one-out analysis, subgroup analyses and meta-regression to explore the sources of heterogeneity and the stability of the summary results.ResultsA total of 743 GC patients with radical tumorectomy were included prospectively and 516 (69.4%) were positive on H. pylori. H. pylori-positive patients tended to survive longer than -negative ones (HR 0.92, 95%CI: 0.74–1.15), though the tendency was not statistically significant. Cohort studies on the prognosis of GC were retrieved comprehensively by assessing the full-text and 59 published studies, together with the result of our study, were included in the further meta-analysis. The summarized results related the positive status of H. pylori to better overall survival (HR 0.81, 95%CI: 0.72–0.90) and disease-free survival (HR 0.83, 95%CI: 0.67–0.99). Results from subgroup analyses indicated that the pooled magnitude of this association was relatively lower in studies not referring to H. pylori in title and abstract.ConclusionsIn conclusion, gastric cancer patients with H. pylori have a better prognosis than patients of H. pylori negative. More stringent surveillance strategies may be necessary for patients with H. pylori negative at cancer diagnosis.

Prediction of distant metastasis and survival prediction of gastric cancer patients with metastasis to the liver, lung, bone, and brain: research based on the SEER database.

BackgroundGastric cancer (GC) is a globally important disease. It is the 5th most common malignancy and the 4th most common cause of death from cancer in the world. Patients with GC are often at an advanced stage when they are first diagnosed, and their overall prognosis is poor due to locally advanced and distant metastasis. This study sought to establish a predictive model of GC distant metastasis and survival that can be used to guide individualized treatment.MethodsPatients diagnosed with GC from the Surveillance, Epidemiology, and End Results database were enrolled in the study. Univariate and multivariate logistic regression analyses were used to identify risk and prognostic factors for GC patients with distant metastasis. The factors were then used to construct nomograms to predict the probability of distant metastasis and the survival time of GC patients. Receiver operating characteristic (ROC) curve and decision curve analyses were used to verify the prediction ability of the nomograms.ResultsWe established a comprehensive nomogram to predict the survival time of GC patients and 4 nomograms to predict distant metastasis. Nomograms could help oncologists to formulate treatment strategies and provide hospice care under an overall management model.ConclusionsEstablishing a prediction model for distant metastasis and the survival of GC patients is of great clinical significance. The prediction of distant metastasis could help clinicians to make individualized assessments of patients and formulate individualized examination measures. Survival prediction models could help oncologists to formulate good treatment strategies and provide hospice care.

Knockdown of PGM1 enhances anticancer effects of orlistat in gastric cancer under glucose deprivation

BackgroundPhosphoglucomutase 1 (PGM1) acts as an important regulator in glucose metabolism. However, the role of PGM1 in gastric cancer (GC) remains unclear. This study aims to investigate the role of PGM1 and develop novel regimens based on metabolic reprogramming in GC.MethodsCorrelation and enrichment analyses of PGM1 were conducted based on The Cancer Genome Atlas database. Data derived from the Kaplan–Meier Plotter database were analyzed to evaluate correlations between PGM1 expression and survival time of GC patients. Cell counting kit-8, 5-Ethynyl-2-deoxyuridine, flow cytometry assays, generation of subcutaneous tumor and lung metastasis mouse models were used to determine growth and metastasis in vitro and in vivo. Cell glycolysis was detected by a battery of glycolytic indicators, including lactate, pyruvic acid, ATP production and glucose uptake. Fatty Acid Synthase (FASN) activity and expression levels of lipid enzymes were determined to reflect on lipid metabolism.ResultsCorrelation and enrichment analyses suggested that PGM1 was closely associated with cell viability, proliferation and metabolism. PGM1 was overexpressed in GC tissues and cell lines. High PGM1 expression served as an indicator of shorter survival for specific subpopulation of GC patients. It was also correlated with pathological tumor stage and pathological tumor node metastasis stage of GC. Under the glucose deprivation condition, knockdown of PGM1 significantly suppressed cell viability, proliferation and glycolysis, whereas lipid metabolism was enhanced. Orlistat, as a drug that was designed to inhibit FASN activity, effectively induced apoptosis and suppressed lipid metabolism in GC. However, orlistat conversely increased glycolytic levels. Orlistat exhibited more significant inhibitive effects on GC progression after knockdown of PGM1 under glucose deprivation due to combination of glycolysis and lipid metabolism both in vitro and in vivo.ConclusionsDownregulation of PGM1 expression under glucose deprivation enhanced anti-cancer effects of orlistat. This combination application may serve as a novel strategy for GC treatment.

Aberrant Non-Coding RNA Expressed in Gastric Cancer and Its Diagnostic Value.

Gastric cancer (GC) is one of the digestive tract malignancies with high invasion and mortality rates. Recent studies have reported that non-coding RNAs (ncRNAs) seem to play a crucial part in many tumors. Due to their high stability, ncRNAs may used as novel biomarkers to predict the occurrence and prognosis of GC. Here, we measured miRNA, lncRNA and cirRNA expression profiles of GC patients by using microarray and RNA-sequencing data from tissue samples. The diagnosis prediction model based on the ncRNA signatures and clinical features was evaluated by circulating and tissue validation and ROC analysis. Nine miRNAs and eight lncRNAs were obtained from the microarray analysis. Six miRNAs (miR-550a-5p, miRNA-936, miR-1306-3p, miR-3185, miR-6083, miR-6792-3p) and three lncRNAs (lnc-MB21D1-3:5, lnc-PSCA-4:2 and lnc-ABCC5-2:1) were abnormally expressed in circulating and tissue samples compared with normal control (NC), which was closely related to clinical pathology and survival time of GC patients; circRNA sequencing and qRT-PCR revealed four circRNAs (circASHL2, circCCDC9, circNHSL1 and cirMLLT10) were abnormally expressed in GC tissues and parts of them were negative relationship with their predicted binding miRNAs. These ncRNAs might act as promising molecular markers for the diagnosis and prognosis of gastric cancer.

Downregulated CMTM8 Correlates with Poor Prognosis in Gastric Cancer Patients.

This study aimed to examine the expression and clinical significance of chemokine-like factor-like MARVEL transmembrane domain-containing family member 8 (CMTM8) in gastric cancer (GC). The mRNA and protein expression of CMTM8 were detected by bioinformatics analysis and immunohistochemistry (IHC), respectively. Bioinformatics analysis found that there was a high mRNA expression of CMTM8 in GC tissues, but failed to identify a significant relationship with the clinicopathological features or prognosis of GC patients. However, IHC results showed that the positive expression of CMTM8 protein in GC tissues was significantly lower than that of adjacent nontumor tissues and correlated with differentiation, tumor node metastasis stage, and distal metastasis of GC patients (p < 0.05). Moreover, the survival time of GC patients with negative CMTM8 protein expression group was shorter than that of positive CMTM8 protein expression group by Kaplan-Meier survival analysis (p < 0.05). Cox proportional hazards model (COX) regression analysis indicated that CMTM8 protein was an independent protective factor for the overall survival of GC patients. Further Gene Set Enrichment Analysis suggested that CMTM8 may be involved in regulating the calcium signaling pathway, cell adhesion molecules, and cytokine-cytokine receptor interaction in GC. Our study shows that CMTM8 protein is downregulated in GC tissues, and CMTM8 protein expression is related to GC metastasis and the prognosis of GC patients.

Protein interacting with C-kinase 1 is involved in epithelial-mesenchymal transformation and suppresses progress of gastric cancer.

Protein interacting with C-kinase 1 (PICK1) is a 415-aa multidomain scaffold protein encoded by the PICK1 gene. Accumulating evidence suggests that PICK1 is involved in the progression of cancer. However, the role of PICK1 in gastric cancer (GC) remains largely unknown. Using integrated analysis of publicly available GC transcriptome data from the Gene Expression Omnibus (GEO) database and immunohistochemistry analysis of samples obtained from clinical GC patients, we found that PICK1 expression was significantly down-regulated in gastric tumor tissues in comparison with adjacent normal tissues. Our analyses also revealed that decreased expression of PICK1 conferred a disadvantage on overall survival time in GC patients. Additionally, PICK1 expression showed a strong association with the epithelial-mesenchymal transition (EMT) pathway, and PICK1 might represent a functional bridge for EMT. Moreover, PICK1 expression was significantly decreased in the EMT subtype of GC and was negatively correlated with the expression of fibronectin 1 (FN1) and myosin light chain 9 (MYL9) mRNAs. Thus, our study provides evidence that PICK1 is a promising biomarker for the molecular etiology of GC.

Comprehensive Analysis of Survival-Related lncRNAs, miRNAs, and mRNAs Forming a Competing Endogenous RNA Network in Gastric Cancer.

To analyze and construct a survival-related endogenous RNA (ceRNA) network in gastric cancer (GC) with lymph node metastasis, we obtained expression profiles of long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs) in GC from The Cancer Genome Atlas database. The edgeR package was used to screen differentially expressed lncRNAs, mRNAs, and miRNAs between GC patients with lymphatic metastasis and those without lymphatic metastasis. Then, we used univariate Cox regression analysis to identify survival-related differentially expressed RNAs. In addition, we used multivariate Cox regression analysis to screen lncRNAs, miRNAs, and mRNAs for use in the prognostic prediction models. The results showed that 2,247 lncRNAs, 155 miRNAs, and 1,253 mRNAs were differentially expressed between the two patient groups. Using univariate Cox regression analysis, we found that 395 lncRNAs, eight miRNAs, and 180 mRNAs were significantly related to the survival time of GC patients. We next created a survival-related network consisting of 59 lncRNAs, seven miRNAs, and 36 mRNAs. In addition, we identified eight RNAs associated with prognosis by multivariate Cox regression analysis, comprising three lncRNAs (AC094104.2, AC010457.1, and AC091832.1), two miRNAs (miR-653-5p and miR-3923), and three mRNAs (C5orf46, EPHA8, and HPR); these were used to construct the prognostic prediction models, and their risk scores could be used to assess GC patients’ prognosis. In conclusion, this study provides new insights into ceRNA networks in GC and the screening of prognostic biomarkers for GC.

Circulating circRNA Has_Circ_0141633 Serves as a Potential Biomarker for Gastric Cancer

The current study aims to investigate the expression of circRNA has_circ_0141633 in the tissues and serum of patients with gastric cancer (GC). RT-qPCR was used to detect the expression of has_circ_0141633 in the tissues and serum of patients with GC. Pearson's correlation was used to analyze the relationship between the level of serum and tissue has_circ_0141633 in GC patients. Receiver characteristic curve (ROC) was used to evaluate the diagnostic value of the expression of serum has_circ_0141633 in GC patients. The relationship between serum has_circ_0141633 and the clinicopathological characteristic was analyzed in GC patients. Kaplan-Meier method was used to analyze the survival rate. The level of serum and tissue has_circ_0141633 in GC patients was significantly higher than that in controls. Pearson's correlation analysis showed a positive correlation between serum and tissue has_circ_0141633 levels (r = 0.846, p < 0.05). ROC curve analysis showed that the AUC of serum has_circ_0141633 was 0.835 (95% CI: 0.753 - 0.916), with the sensitivity and specificity of 84.5% and 93.6%. The level of serum has_circ_0141633 was significantly increased according to the malignant characteristics of tumor diameter, differentiation, lymph node metastasis, and TNM stage. The median survival time of GC patients with low expression of has_circ_0141633 was longer than that of GC patients with high expression of has_circ_0141633. In summary, upregulation of serum has_circ_0141633 may be expected to be a specific molecular marker for the diagnosis and evaluation of malignant GC.

SMADs binding site polymorphisms rs9911630 is associated with susceptibility but not prognosis of gastric cancer: a case control study.

Background: Single nucleotide polymorphisms (SNPs) in transcription factor binding sites (TFBS) can change their binding strength, affecting the function of transcription factors (TFs). Small mother against decapentaplegic (SMAD) proteins are known as a family of TFs involved in tumorigenesis. We performed this study to investigate whether SNPs in SMADs binding sites affect the susceptibility or prognosis of gastric cancer (GC).Methods: Using bioinformatics tools, we focused on the association between rs9911630 polymorphism and GC. We performed this case-control study in 1275 GC patients and 1426 cancer-free subjects using TaqMan allelic discrimination method.Results: We found that rs9911630 A>G polymorphism was associate to an increased risk of gastric cancer (adjusted OR for additive model = 1.16; 95% CI = 1.03-1.30). Furthermore, we assess whether rs9911630 polymorphism affected the prognosis of GC. However, no significant association was discovered between rs9911630 A>G polymorphism and overall survival time of GC patients (HR for addictive model = 1.01; 95%CI = 0.88-1.15).Conclusions: Our results suggested that rs9911630 polymorphism in SMADs target site might influence susceptibility but not prognosis of gastric cancer.

Development and Validation of a Prognostic Nomogram for Gastric Cancer Based on DNA Methylation-Driven Differentially Expressed Genes.

Background/Aims: The incidence of gastric cancer (GC) ranks fifth among common tumors and GC is the third leading cause of cancer-related death worldwide. The aim of this study was to develop and validate a nomogram for predicting the overall survival (OS) of patients with GC.Methods: DNA methylation (DNAm)-driven genes were identified by integrating DNAm and gene expression profiling analyses from The Cancer Genome Atlas (TCGA) GC cohort. Then, a risk score model was built based on Kaplan-Meier (K-M), least absolute shrinkage and selector operation (LASSO), and multivariate Cox regression analyses. After analyzing the clinical parameters, a nomogram was constructed and assessed. Another cohort (GSE62254) was used for external validation.Results: Thirteen differentially expressed DNAm-driven genes were narrowed down to a six-gene signature (PODN, NPY, MICU3, TUBB6 and RHOJ were hypermethylated, and MYO1A was hypomethylated), which was associated with OS (P < 0.05) after survival and LASSO regression analyses. These differentially expressed genes (DEGs) with altered DNAm statuses were included in the prognostic risk score model. The univariate Cox regression analysis indicated that risk score, age, and number of positive lymph nodes were significantly associated with survival time in GC patients. The multivariate Cox regression analysis also indicated that these variables were significant prognostic factors for GC. A nomogram including these variables was constructed, and its performance in predicting the 1-, 3- and 5-year survival outcomes of GC patients was estimated through time-dependent receiver operating characteristic (ROC) curves. In addition, the clinical benefit of this model was revealed by decision curve analysis (DCA). Pathway enrichment analysis suggested that these DNAm-driven genes might impact tumor progression by affecting signaling pathways such as the “ECM RECEPTOR INTERACTION” and “DNA REPLICATION” pathways.Conclusions: The altered status of the DNAm-driven gene signature (PODN, MYO1A, NPY, MICU3, TUBB6 and RHOJ) was significantly associated with the OS of GC patients. A nomogram incorporating risk score, age and number of positive lymph nodes can be conveniently used to facilitate the individualized prediction of OS in patients with GC.

Comprehensive analysis of the regulatory network of differentially expressed mRNAs, lncRNAs and circRNAs in gastric cancer

Gastric cancer (GC) is one of the most common types of human cancers. However, the mechanisms underlying GC remained largely unclear. To determine whether the differentially expressed mRNAs, lncRNAs and circRNAs in GC, we screened conducted SBC-ceRNA microarray analysis in 3 pairs of GC and normal tissues. Furthermore, differentially expressed mRNAs mediated protein protein interaction (PPI) networks, lncRNAs mediated cis-regulatory network, and circRNA mediated ceRNA network were for the first time constructed to reveal their potential functions and mechanisms in GC. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was conducted to validate the microarray analysis. A total of 922 mRNAs, 2112 lncRNAs and 2896 circRNAs were observed to be dysregulated in GC samples. Bioinformatics analysis showed these differentially expressed genes (DEGs) were significantly associated with regulating branched − chain amino acid catabolic process, Glycolysis/Gluconeogenesis and ARF protein signal transduction. Moreover, we found the dysregulation of key mRNAs and lncRNAs were associated with the overall survival time in GC patients. We believe this study provides useful information for understanding the mechanism underlying GC progression and exploring potential therapeutic and prognostic targets for GC.