Value In Gastric Cancer Research Articles

Clinicopathological significance and prognostic value of polypyrimidine tract binding protein 1 (PTBP1) in gastric cancer.

BackgroundPolypyrimidine tract binding protein 1 (PTBP1) is a member of heterogeneous nuclear ribonucleoprotein (hnRNP) family and has recently been reported to contribute to development and progression of various tumors. However, the clinicopathological significance and prognostic value of PTBP1 in gastric cancer have not been sufficiently elucidated.MethodsBioinformatic analysis of The Cancer Genome Atlas (TCGA) data were employed to analyze the expression of PTBP1 mRNA and its prognostic value in gastric cancer. The expression type of PTBP1 in gastric cancer cells was further confirmed through reverse transcription polymerase chain reaction (RT-PCR) and western blot assay. Then, the association between PTBP1 protein expression and clinicopathological features was analyzed based on immunohistochemical staining results in gastric cancer tissue microarray including 311 cases. The prognostic value of PTBP1 protein was explored through univariate and multivariate analyses. Additionally, cell count and transwell assay were performed to detect the biological role of PTBP1 in gastric cancer cells in vitro.ResultsPTBP1 was highly expressed in gastric cancer cells and tissues at mRNA and protein level. High expression of PTBP1 was closely related to several clinicopathological features, including gender, age at surgery, histological type, TNM stage and lymph node metastasis. Moreover, high expression PTBP1 predicts poor prognosis, and may be an independent prognostic factor for overall survival in gastric cancer patients. Knockdown of PTBP1 substantially suppressed the proliferation, migration and invasion of gastric cancer cells in vitro.ConclusionsPTBP1 is up-regulated and predicts poor prognosis in gastric cancer. PTBP1 may serve as a biomarker of poor prognosis and a novel target in treating gastric cancer.

Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis.

Background: Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods. Methods: DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein–protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted. Results: Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1. Conclusion: ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.

In silico development and validation of a novel glucose and lipid metabolism-related gene signature in gastric cancer.

BackgroundAbnormal glucose and lipid metabolism plays a critical role in gastric carcinogenesis and development. Hence, we presented a systematic analysis of glucose and lipid metabolism-related genes to explore their function and prognostic value in gastric cancer (GC).MethodsThe consensus clustering algorithm was used to identify the molecular subtypes based on glucose and lipid metabolism-related genes. Subsequently, cox regression analysis and lasso regression analysis were utilized to establish a risk prediction model. A clinical nomogram was constructed to assist prognosis assessment. In addition, ESTIMATE and single-sample gene set enrichment analysis (ssGSEA) algorithms were performed to evaluate the immune infiltration of the metabolic model, and GSEA was used for enrichment analysis of the metabolic signature. Finally, we explored the association between the risk model and anti-cancer therapy for the purpose of clinical application for GC treatment.ResultsGC samples were divided into 2 subtypes based on glucose and lipid metabolism-related genes, patients in cluster 2 had a better overall survival (OS) than those in cluster 1. Fifty-two genes were identified by univariable regression analysis. Finally, a 13-gene metabolic signature (CACNA1H, CHST1, IGFBP3, NASP, STC1, VCAN, NUP205, NUP43, PGM2L1, CAV1, ELOVL4, PRKAA2, TNFAIP8L3) was successfully constructed that demonstrated good performance in different datasets, as well as an independent hazardous factor for prognosis. In addition, the nomogram constructed with the clinical variables showed higher predictive efficacy for predicting the 1-, 3-, and 5-year OS. The 13-gene metabolic signature was significantly associated with immune scores and immune cell infiltration in high-risk group. Moreover, GSEA analysis revealed that cancer- and immune-related pathways were enriched in the high-risk group. Finally, our results indicated that there might exist an immunosuppressive status in the high-risk groups.ConclusionsThis study demonstrated that glucose and lipid metabolism-related genes were significantly associated with prognosis. Meanwhile, it will provide novel insights into exploring the immunoregulation roles of these genes.

High Prolyl 4-Hydroxylase Subunit Alpha 3 Expression as an Independent Prognostic Biomarker and Correlated With Immune Infiltration in Gastric Cancer.

Background: Gastric cancer (GC) has a high mortality rate and is particularly prevalent in China. The extracellular matrix protein, prolyl 4-hydroxylase subunit alpha 3 (P4HA3), has been implicated in various cancers. We aimed to assess the diagnostic and prognostic value of P4HA3 in GC and investigate its correlation with immune cell infiltration. Methods: The present study used microarray data from the Cancer Genome Atlas (TCGA) to analyze the association of P4HA3 expression with clinicopathological features. Data from the Gene Expression Omnibus (GEO) were used for validation. Receiver operating characteristic (ROC) and Kaplan–Meier curves were constructed to determine the diagnostic and prognostic value of P4HA3 in GC. Univariate and multivariate regression analyses were performed to assess the impact of P4HA3 on overall survival (OS) rates. A protein–protein interaction (PPI) network was generated and functional enrichment evaluated. Single-sample gene set enrichment analysis (ssGSEA) was conducted to correlate P4HA3 expression with immune cell infiltration. The correlation between P4HA3 and immune check point genes was studied. Results: P4HA3 was over-expressed in GC, along with 15 other types of cancer, including breast invasive carcinoma and cholangiocarcinoma. P4HA3 showed high diagnostic and prognostic value in GC and was an independent prognostic factor. P4HA3, TNM (tumor, node, metastases) stage, pathological stage and age all correlated with OS rates. Genes related to P4HA3 were enriched in the lumen of the endoplasmic reticulum and included procollagen-proline 3-dioxygenase activity. P4HA3 expression correlated with numbers of macrophages, natural killer (NK) cells, immature dendritic cells (iDC), mast cells, eosinophils, effective memory T cells (Tem), T-helper 1 (Th1) cells and dendritic cells (DC). P4HA3 was positively correlated with hepatitis A virus cellular receptor 2 (HAVCR2) and programmed cell death 1 ligand 2 (PDCD1LG2). Conclusion: P4HA3 is a potential independent biomarker for prognosis of GC and may be an immunotherapy target in the treatment of GC.

Clinicopathological and Prognostic Value of USP22 Expression in Gastric Cancer: A Systematic Review and Meta-Analysis and Database Validation.

BackgroundIt has been reported that there is a correlation between the level of ubiquitin-specific protease 22 (USP22) and the clinicopathological parameters and prognosis of gastric cancer (GC) patients, but the conclusions are inconsistent. Hence, a meta-analysis must be conducted to clarify the relationship between USP22 expression and clinicopathological and prognostic value of GC patients to provide more accurate evidence.MethodsAccording to the predetermined selection criteria, systematic file retrieval was performed. The hazard ratio (HR) or odds ratio (OR) and its 95% confidence interval (CI) were used to evaluate the relationship between USP22 expression and clinicopathological and prognostic value of GC patients.ResultsIn a total of 802 patients, those with GC were finally included in 6 studies. The pooled results demonstrated that the expression of USP22 was significantly increased in GC tissues compared with control tissues (OR = 9.947, 95% CI, 6.074–16.291, P = 0.000), and USP22 expression was related to lymph node metastasis (OR = 2.415, 95% CI, 1.082, P = 0.031), distant metastasis (OR = 3.956, 95% CI, 1.365–11.464, P = 0.011) and TNM stage (OR = 2.973, 95% CI, 1.153–7.666, P = 0.024). Nevertheless, the expression of USP22 was not correlated with gender (OR = 1.202, 95% CI, 0.877–1.648, P = 0.253), age (OR = 1.090, 95% CI, 0.811–1.466, P = 0.568), tumor size (OR = 0.693,95% CI, 0.348–1.380, P = 0.297), tumor differentiation (OR = 1.830, 95%CI, 0.948–3.531, P = 0.072) and depth of invasion (OR = 2.320, 95% CI, 0.684–7.871, P = 0.177). Moreover, a high expression of USP22 predicted a poor overall survival (OS) in GC patients (HR = 2.012, 95% CI, 1.522–2.658, P = 0.000). The database of Kaplan–Meier plotter confirmed that a high expression of USP22 was correlated with poor prognostics in GC patients (HR = 1.41, 95% CI, 1.18–1.68, P < 0.01).ConclusionUSP22 overexpression in GC tissues is positively related to lymph node metastasis, distant metastasis and TNM stage and indicates a poor clinical outcome of GC patients, but it is not associated with age, gender, depth of invasion, tumor differentiation and tumor size of GC patients.Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: 338361.

Abstract 5844: A comprehensive pan-cancer analysis of MDM2/MDM4 gene amplification in Chinese solid cancer patients

Abstract Background: Many patients with cancer have benefited from immunotherapy represented by the blockade of immune checkpoint PD-1/PD-L1. However, about 4-29% of cancer patients treated with immunotherapy developed hyper-progressive diseases(HPD) with accelerated tumor growth. MDM2/MDM4 amplification was suggested as genomic correlates for elevated risk hyperprogression. The objective of this study was to evaluate the frequency of amplification of MDM2/MDM4 in the Chinese solid tumor patients and to provide advice on the selecting of optimal treatment decisions. Methods: Tumor or blood samples were collected from 2,937 patients with solid cancer, genetic mutations and amplification was detected using the next-generation sequencing(NGS). Results: A total 112 patients with MDM2/MDM4 amplification were identified, including lung cancer 50.9% (57/112), colorectal cancer 14.3% (16/112), gastric cancer 8.0% (9/112), liver cancer 5.4% (6/112), Biliary tract cancers 4.5% (5/112), breast cancer 2.7% (3/112), and pancreatic ductal adenocarcinoma 2.7% (3/112). TMB value was identified, The median TMB for lung cancer was 9.13 mutations/Mb, median TMB for colorectal cancer was 13.8 mutations/Mb, a high TMB value in gastric cancer (median TMB=20.22 mutations/Mb), and median TMB for liver cancer was 17.9 mutations/Mb. Meanwhile, MSI was detected in 8% of patients with MDM2/MDM4 amplification, of which 3 in lung cancer, 5 in colorectal cancer, and 1in gastric cancer. Conclusions: Although amplification of MDM2/MDM4 was observed only in a small proportion of patients, it demonstrated an association with high TMB in several common cancer types. In addition, our data indicate that amplification of MDM2/MDM4 in different types of cancer is heterogeneous and that an appropriate immunotherapy strategy for patients with solid cancer should be noted. Citation Format: xiangyu sun, Zhichao Fu. A comprehensive pan-cancer analysis of MDM2/MDM4 gene amplification in Chinese solid cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5844.

Expression of miR-4739 in Gastric cancer and its Relationship with Clinical Pathological Features of Patients.

ObjectiveTo investigate the expression level of miR-4739 in gastric cancer (GC), analyze its diagnostic value in GC and the relationship with clinical pathological characteristics, and analyze its impact on the prognosis of patients.MethodsA total of 96 patients with GC who underwent radical gastrectomy in our hospital from March 2017 to June 2021 were selected. GC tissues from all patients were collected, and normal tissues adjacent to cancer were collected as controls. The expression level of miR-4739 in tissues was detected, the relationship between miR-4739 and different pathological features was analyzed, and the diagnostic value of miR-4739 in GC was analyzed. All patients were followed up after the operation, and the survival time of the patients was set as from the day of the first operation to 1 d when the patients died or the follow-up ended.ResultsThe relative expression level of miR-4739 in the GC tissue was (0.39 ± 0.06), lower than that in the paracancerous tissue (1.18 ± 0.19) (P < 0.05). The AUC of miR-4739 in the diagnosis of GC was 0.705. When the Youden index was 0.320 and the optimal cutoff value was 0.37, the sensitivity was 95.30% and the specificity was 36.70%. The expression level of miR-4739 in our patient was related to the differentiation degree, lymph node metastasis, tumor diameter, and TNM stage (P < 0.05). During the follow-up period, 26 of 96 patients died, and the survival rate was 72.92% (26/96). The median survival time was 29 months in the miR-4739 LE group, which was shorter than 39 months in the miR-4739 HE group (P < 0.05). Univariate analysis showed that age, degree of differentiation, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all related to the prognosis of the patient (P < 0.05). Multivariate analysis showed that differentiation degree, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all independent factors affecting the prognosis of the patients (P < 0.05).ConclusionThe expression of miR-4739 in GC tissue was down-regulated, and its level was related to the degree of differentiation, lymph node metastasis, tumor diameter, and TNM stage. The expression level of miR-4739 has certain diagnostic value for patients with GC, and the prognosis of patients in LE group was worse than that in HE group.

Differential expression of metallothionein and p21 in gastric cancer and some precursor lesions.

Gastric cancer (GC) is a heterogeneous disease with molecular diversity between and within tumors; therefore, searching for altered genes within this cancer is mandatory to reach the proper individualized targeted therapy. Expressions of Metallothionein (MT) and p21 are not uniform in various types of cancers and their predictive value in GC is controversial. This study aimed to assess the role of MT and p21 in intestinal-type GC and some of its precursor lesions. Immunohistochemical staining for MT and p21 was applied on paraffin blocks belonging to 30 GCs and 51 benign gastric lesions/precancerous lesions [33 chronic gastritis and 18 chronic gastritis with gastric intestinal metaplasia (GIM)]; 27 of them were associated with H. pylori infection. MT expression was dramatically increased while p21 expression was dramatically decreased from chronic gastritis to GIM to GC. In precancerous lesions, H. pylori-positive cases had significantly higher MT expression and lower p21 expression compared to H. pylori-negative cases. In GCs, decreased expression of both MT and p21 was associated with high-grade and advanced-stage cancers. Both MT and p21 may have a role in the development and progression of GC, and both proteins may be useful for selecting targeted therapy for GC patients.

The dynamic alteration of transcriptional regulation by crucial TFs during tumorigenesis of gastric cancer

BackgroundThe mechanisms of Gastric cancer (GC) initiation and progression are complicated, at least partly owing to the dynamic changes of gene regulation during carcinogenesis. Thus, investigations on the changes in regulatory networks can improve the understanding of cancer development and provide novel insights into the molecular mechanisms of cancer.MethodsDifferential co-expression analysis (DCEA), differential gene regulation network (GRN) modeling and differential regulation analysis (DRA) were integrated to detect differential transcriptional regulation events between gastric normal mucosa and cancer samples based on GSE54129 dataset. Cytological experiments and IHC staining assays were used to validate the dynamic changes of CREB1 regulated targets in different stages.ResultsA total of 1955 differentially regulated genes (DRGs) were identified and prioritized in a quantitative way. Among the top 1% DRGs, 14 out of 19 genes have been reported to be GC relevant. The four transcription factors (TFs) among the top 1% DRGs, including CREB1, BPTF, GATA6 and CEBPA, were regarded as crucial TFs relevant to GC progression. The differentially regulated links (DRLs) around the four crucial TFs were then prioritized to generate testable hypotheses on the differential regulation mechanisms of gastric carcinogenesis. To validate the dynamic alterations of gene regulation patterns of crucial TFs during GC progression, we took CREB1 as an example to screen its differentially regulated targets by using cytological and IHC staining assays. Eventually, TCEAL2 and MBNL1 were proved to be differentially regulated by CREB1 during tumorigenesis of gastric cancer.ConclusionsBy combining differential networking information and molecular cell experiments verification, testable hypotheses on the regulation mechanisms of GC around the core TFs and their top ranked DRLs were generated. Since TCEAL2 and MBNL1 have been reported to be potential therapeutic targets in SCLC and breast cancer respectively, their translation values in GC are worthy of further investigation.

Two New 3D Supramolecular Complexes: Photocatalytic Properties and Treatment Activity for Gastric Cancer.

Two new coordination polymers, [Cu₂(5-MeO-Hip)₄(py)₄]n (1) and [Co(5-EtO-ip)(4,4'-bipy)]n·n(MeOH) (2) (5-MeO-H₂ip is 5-methoxyisophthalic acid, 5-EtO-H₂ip is 5-ethoxyisophthalic acid, py is pyridine, and 4,4'-bipy is 4,4'-bipyridine), were created via solvothermal self-assembly. The thermal steadiness and photocatalytic functions of 1 and 2 were detected, and their application values in gastric cancer and the related mechanism were discussed. CCK-8 assay was used to determine the inhibitory activity toward gastric cancer cells' viability, and real-time RT-PCR was employed to examine the gastric cancer cells' Notch signaling pathway activity.

Biological and clinical implications of hsa_circ_0086720 in gastric cancer and its clinical application.

BackgroundCircular RNAs (circRNAs) are thought to be vital participants in carcinogenesis and have the characteristics of being stable, specific, and well conserved. However, their clinical significance and application value in gastric cancer (GC) are still poorly understood. Hsa_circ_0086720 was found to be a dysregulated circRNA in GC by microarray screening and was further explored for its clinical significance and application.MethodsHsa_circ_0086720 was detected in GC cell lines, tissues, and plasma, and the clinicopathological correlations were investigated. The existence, stability, origin, and change in the plasma hsa_circ_0086720 level were verified in early GC patients. Moreover, receiver operating characteristic and Kaplan–Meier survival curves were constructed to analyze the diagnostic and prognostic values, and bioinformatics analysis was used to identify the potential functions. Finally, risk factors and nomogram predicting were established.ResultsHsa_circ_0086720 was found to be downregulated in gastric carcinogenesis, and tissue hsa_circ_0086720 was negatively associated with perineural invasion, Borrmann type, disease‐free survival, and overall survival. Hsa_circ_0086720 was stable in circulating plasma and was actively secreted by cells in gastric carcinogenesis. As a biomarker for early GC screening, plasma hsa_circ_0086720 had good sensitivity and specificity, and its stability met the clinical application requirements. Bioinformatics analysis suggested that dysregulated hsa_circ_0086720 has important functions in gastric carcinogenesis. Univariate Cox regression analysis identified factors associated with overall survival time and disease‐free survival time. The nomograms showed good accuracy of predicting survival time.ConclusionHsa_circ_0086720 is a novel biomarker for screening early GC and predicting the prognosis of advanced‐stage patients.

CD44v6 high membranous expression as a predictive marker of therapy response in patients with gastric cancer.

342 Background: In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Methods: Two GC surgical cohorts, from Portugal and South Korea (n = 964), were characterized for the extension of CD44v6 membranous immunoexpression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting response to treatment and its impact on prognosis was determined. Results: High CD44v6 expression was associated with invasive features (perineural invasion and depth of invasion) in both cohorts and with worse survival in the Portuguese GC cohort (HR 1.461; 95% confidence interval 1.002–2.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p &lt; 0.05), particularly those with heterogeneous CD44v6- positive and -negative populations (CD44v6_3+) (p &lt; 0.007 and p &lt; 0.009). Conclusions: Our study is the first to identify CD44v6 high membranous expression as a potential predictive marker of response to conventional treatment, but it does not clarify CD44v6 prognostic value in GC. Importantly, our data support selection of GC patients with high CD44v6-expressing tumors for conventional chemotherapy in addition to surgery. These findings will allow better stratification of GC patients for treatment, potentially improving their overall survival.

Functional genetic variants in complement component 7 confer susceptibility to gastric cancer.

BackgroundComplement system plays an important role in innate immunity which involved in the changes tumor immune microenvironment by mediating the inflammatory response. This study aims to explore the relationship between complement component 7 (C7) polymorphisms and the risk of gastric cancer (GC).Materials and MethodsAll selected SNPs of C7 were genotyped in 471 patients and 471 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional Logistic regression to analyze the relationship between each genotype and the genetic susceptibility to gastric cancer. The level of C7 expression in GC was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) and detected by Enzyme Linked Immunosorbent Assay. Kaplan–Meier plotter were used to reveal C7 of prognostic value in GC. We examined SNPs associated with the expression of C7 using the GTEx database. The effect of C7 polymorphisms on the regulatory activity of C7 was detected by luciferase reporter assay.ResultsUnconditional logistic regression showed that individuals with C7 rs1376178 AA or CA genotype had a higher risk of GC with OR (95% CI) of 2.09 (1.43–3.03) and 1.88 (1.35–2.63), respectively. For C7 rs1061429 C > A polymorphism, AA genotype was associated with the elevated risk for developing gastric cancer (OR = 2.16, 95% CI [1.37–3.38]). In stratified analysis, C7 rs1376178 AA genotype increased the risk of GC among males (OR = 2.88, 95% CI [1.81–4.58]), but not among females (OR = 1.06, 95% CI [0.55–2.06]). Individuals carrying rs1061429 AA significantly increased the risk of gastric cancer among youngers (OR = 2.84, 95% CI [1.39–5.80]) and non-smokers (OR = 2.79, 95% CI [1.63–4.77]). C7 was overexpressed in gastric cancer tissues and serum of cancer patients and was significantly associated with the prognosis. C7 rs1061429 C > A variant contributed to reduced protein level of C7 (P = 0.029), but rs1376178 didn’t. Luciferase reporter assay showed that rs1376178C-containing plasmid exhibited 2.86-fold higher luciferase activity than rs1376178 A-containing plasmid (P < 0.001). We also found that rs1061429A allele contributed 1.34-fold increased luciferase activity than rs1061429C allele when co-transfected with miR-591 (P = 0.0012).ConclusionsThese findings highlight the role of C7 in the development of gastric cancer.

Predictive value of nomogram based on Kyoto classification of gastritis to diagnosis of gastric cancer

Background and Aim It is important to predict the risk of gastric cancer (GC) for endoscopists because early detection of GC determines the selection of the best treatment strategy and the prognosis of patients. The study aimed to evaluate the utility of a predictive nomogram based on the Kyoto classification of gastritis for GC. Methods It was a retrospective study that included 2639 patients who received esophagogastroduodenoscopy and serum pepsinogen (PG) assay from January 2019 to November 2019 at the Endoscopy Center of the Department of Gastroenterology, Wenzhou Central Hospital. Routine biopsy was conducted to determine the benign and malignant lesions pathologically. All cases were randomly divided into the training set (70%) and the validation set (30%) by using the bootstrap method. A nomogram was formulated according to multivariate analysis of the training set. The predictive accuracy and discriminative ability of the nomogram were assessed by concordance index (C-index), area under the curve (AUC) of receiver operating characteristic curve (ROC) as well as calibration curve and were validated by the validation set. Results Among all patients enrolled, 102 of 2636 cases showed LGIN, HGIN and gastric cancer pathology results, whereas the rest cases showed benign pathological results. Multivariate analysis indicated that age, sex, PG I/II ratio and Kyoto classification scores were independent predictive variables for GC. The C-index of the nomogram of the training set was 0.79 (95% CI: 0.74 to 0.84) and the AUC of ROC is 0.79. The calibration curve of the nomogram demonstrated an optimal agreement between predicted probability and observed probability of the risk of GC. The C-index was 0.86 (95% CI: 0.79 to 0.94) with a calibration curve of better concurrence in the validation set. Conclusion The nomogram formulated was proven to be of high predictive value for GC.

Prognostic Value of the Combination of HB (hemoglobin) and CEA in Resectable Gastric Cancer.

Objective: In order to investigate the prognostic value of a novel biomarker combining serum carcinoembryonic antigen (CEA) and hemoglobin (HB) levels in patients with resectable gastric cancer.Introduction: This retrospective study assessed the relationship between CEA, hemoglobin levels, a novel combined prognostic biomarker (HB-CEA) and clinicopathological features of gastric cancer. Their prognostic values in gastric cancer were also analyzed.Materials and Methods: This retrospective study evaluated the CEA, hemoglobin levels and clinicopathological features of patients with resectable gastric cancer. Kaplan-Meier curves, univariate and multivariate Cox proportional models were used to determine the prognostic significance of these factors for overall survival (OS) in the training and validation sets (n=353 and n=388, respectively). Based on optimal cutoff values of CEA and hemoglobin (3.395 ng/mL and 125.5 g/L, respectively), patients were stratified into three groups: HB-CEA=0, 1, and 2 (CEA <3.395 ng/mL and HB ≥125.5 g/L; CEA ≥3.395 ng/mL or HB <125.5 g/L; and CEA ≥3.395 ng/mL and HB <125.5 g/L, respectively).Results: The area under the curve was larger for HB-CEA than for either HB or CEA alone (training set: 0.677, 0.650, and 0.629; validation set: 0.670, 0.605, and 0.605, respectively). HB-CEA was strongly associated with age, tumor size, differentiation, pathological TNM stage (pTNM), depth of tumor invasion, lymph node metastasis, and survival status (all p<0.05). A higher HB-CEA score correlated with poor survival (Kaplan-Meier curves, all p<0.05). Multivariate analysis showed that HB-CEA was an independent prognostic factor for OS (p<0.05).Conclusion: Preoperative HB-CEA, as a potential novel hematological biomarker, can predict the progression of gastric cancer and the prognosis of patients, and is of great value in guiding clinical practice. Therefore, patients with a higher HB-CEA score should receive more extensive follow-up for early detection and intervention of tumor progression.

Identification and Validation of a Potent Multi-lncRNA Molecular Model for Predicting Gastric Cancer Prognosis.

Gastric cancer (GC) remains the third deadliest malignancy in China. Despite the current understanding that the long noncoding RNAs (lncRNAs) play a pivotal function in the growth and progression of cancer, their prognostic value in GC remains unclear. Therefore, we aimed to construct a polymolecular prediction model by employing a competing endogenous RNA (ceRNA) network signature obtained by integrated bioinformatics analysis to evaluate patient prognosis in GC. Overall, 1,464 mRNAs, 14,376 lncRNAs, and 73 microRNAs (miRNAs) were found to be differentially expressed in GC. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these differentially expressed RNAs were mostly enriched in neuroactive ligand–receptor interaction, chemical carcinogenesis, epidermis development, and digestion, which were correlated with GC. A ceRNA network consisting of four lncRNAs, 21 miRNAs, and 12 mRNAs were constructed. We identified four lncRNAs (lnc00473, H19, AC079160.1, and AC093866.1) as prognostic biomarkers, and their levels were quantified by qRT-PCR in cancer and adjacent noncancerous tissue specimens. Univariable and multivariable Cox regression analyses suggested statistically significant differences in age, stage, radiotherapy, and risk score groups, which were independent predictors of prognosis. A risk prediction model was created to test whether lncRNAs could be used as an independent risk predictor of GC or not. These novel lncRNAs’ signature independently predicted overall survival in GC (p < 0.001). Taken together, this study identified a ceRNA and protein–protein interaction networks that significantly affect GC, which could be valuable for GC diagnosis and therapy.

Combinatorial Analysis of AT-Rich Interaction Domain 1A and CD47 in Gastric Cancer Patients Reveals Markers of Prognosis.

Background: The AT-rich interaction domain 1A (ARID1A) is thought to be a tumor suppressive gene, and most of its mutations result in loss of expression of ARID1A protein. Combined with SIRPα on the surface of macrophages, CD47 on the surface of cancer cells can send an antiphagocytic “Don’t eat me” signal to the immune system that helps to avoid immune surveillance. However, the relationship between ARID1A and CD47 expression and their prognostic value in gastric cancer (GC) are still unknown.Methods: In this study, we evaluated ARID1A and CD47 expression in 154 GC patients’ tissues using tissue microarray. Expressions of ARID1A and CD47 in GC cell lines were determined by western blot and quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) techniques, and cell membranous CD47 expression was quantified by flow cytometry. In addition, chromatin immunoprecipitation (ChIP)–qPCR was used to determine the aspects of regulation of CD47 by ARID1A. The proportions of tumor-infiltrating immune cells were estimated on The Cancer Genome Atlas (TCGA) data set by using quanTIseq and EPIC algorithms. The infiltration of M1-polarized macrophages, M2-polarized macrophages, and regulatory T cells (Tregs) in GC tissues was determined by multispectral immunofluorescence.Results: A significant correlation was found between loss of ARID1A and high expression of CD47 at protein level in GC. By integrating 375 bulk RNA sequencing samples from TCGA data set, we found that mutated ARID1A correlated with high CD47 expression. In GC cell lines, knockdown of ARID1A significantly increased CD47 expression both at protein and mRNA levels as measured by western blot, qRT-PCR, and flow cytometry. Moreover, ChIP-qPCR revealed that CD47 was a direct downstream target gene of ARID1A in GC. Utilizing univariate and multivariate survival analyses, we found that patients with ARID1AlossCD47high expression had a worse prognosis. Estimation of infiltrating immune cells on TCGA data set showed that a higher infiltration proportion of M2 macrophages and Tregs was found in ARID1AmutatedCD47high expression subgroup. Furthermore, application of multispectral immunofluorescence revealed a higher infiltration proportion of M2 macrophages and Tregs in ARID1AlossCD47high GC tissues.Conclusion: Loss of ARID1A is strongly correlated with high CD47 expression in GC, and combination of ARID1A and CD47 is a promising prognosis factor in GC.

Gastrin-17 Combined with CEA, CA12-5 and CA19-9 Improves the Sensitivity for the Diagnosis of Gastric Cancer.

BackgroundPrevious studies reported the utility of serum tumor markers (such as CEA, CA12-5 and CA19-9) and gastrin-17 in the diagnosis of gastric cancer (GC). However, the value of these serum markers for diagnosing GC is still under debate. In this study, we aimed to evaluate the effect of gastrin-17, CEA, CA12-5 and CA19-9 in the diagnosis of GC.MethodsThe level of CEA, CA12-5, CA19-9 and gastrin-17 was tested in 230 GC patients and 99 healthy people. The value of the four markers for diagnosing GC was analyzed.ResultsThe positive rate of Gastrin-17, CEA, CA19-9 and CA12-5 was much higher in GC group (22.61%, 22.61%, 20.00% and 8.26%, respectively) than that of healthy control group (5.05%, 2.02%, 1.01% and 2.02%, respectively). The sensitivity of Gastrin-17, CEA, CA12-5 and CA19-9 in the diagnosis of GC was 22.61%, 22.61%, 6.96% and 20.00%, respectively, and the corresponding specificity was 94.95%, 97.98%, 98.99% and 98.99%, respectively. By using the optimal cut-off value derived from the area under curve (AUC) of receiver operating characteristic curve, the AUC of gastrin-17, CEA, CA12-5, CA19-9 increased to 0.72, 0.64, 0.61 and 0.65, respectively. After combining the four markers, the AUC increased to 0.79 (95% CI: 0.75–0.84), and the corresponding sensitivity and specificity were 65.22% (95% CI: 58.70–71.40%) and 84.85% (95% CI: 76.20–91.30%), respectively, which were significantly higher than those of separate markers (P < 0.05).ConclusionCEA, CA12-5, CA19-9 and gastrin-17 were all valuable in the diagnosis of GC, and gastrin-17 had the best diagnostic value among the four markers. Gastrin-17 combined with CEA, CA12-5 and CA19-9 could improve the diagnostic value of GC significantly. Prospective, multi-center studies are needed to validate our findings.

Clinical Value of Combined Detection of Serum sTim-3 and Pepsinogen for Gastric Cancer Diagnosis.

PurposeThe present study aimed to evaluate the clinical value of the combined detection of soluble T cell immunoglobulinand mucin domain molecule 3 (sTim-3) and pepsinogen (PG) in sera for gastric cancer (GC) diagnosis.Patients and MethodsThe double antibody sandwich method was used to establish a highly sensitive time-resolved fluorescence immunoassay for the detection of sTim-3. Serum sTim-3, PGI, and PGII levels in 149 GC patients (123 first-diagnosis GC patients and 26 post-GC patients), 81 patients with benign gastric disease (BGD), and 73 healthy controls were quantitatively detected. The clinical diagnostic value of the combined detection of sTim-3 and PG in GC was analyzed.ResultsSerum sTim-3 levels in GC (20.41 ± 9.55 ng/mL) and BGD (16.50 ± 9.76 ng/mL) patients were significantly higher (P < 0.001) than those in healthy controls (9.22 ± 3.40 ng/mL). Combined detection of sTim-3 and PGI/PGII (AUC: 0.9330, sensitivity: 86.44%, and specificity: 91.78%) showed a high diagnostic value for GC. When the level of PGI/PGII was less than 12.11 and that of sTim-3 was greater than 14.30 ng/mL, the positive rate of the control group was reduced to 0%, and the positive detection rate of GC was 54.47%. In addition, in post-operative patients, serum sTim-3 levels in the recurrence group (33.56 ± 4.91 ng/mL) were significantly higher than those in the no recurrence group (11.95 ± 5.16 ng/mL).ConclusionsTim-3 levels in BGD and GC sera were significantly higher than those in the control group sera. Additionally, sTim-3 serum levels can predict recurrence in post-operative patients. Compared with PG alone, the combined detection of serum PG and sTim-3 can significantly improve the detection sensitivity and specificity of BGD and GC.

Fragmentation Analysis of Plasma DNA Reveals Its Prognostic Value in Gastric Cancer.

Gastric cancer (GC) is a common cause of cancer-related deaths. The poor clinical outcome in GC patients is partially associated with a lack of appropriate diagnostic and prognostic biomarkers. In the present study, we evaluated the diagnostic and prognostic values of cell-free DNA (cfDNA) integrity and the concentration of circulating nucleosomes (cNUCs). In the study, 40 GC patients and 55 GC-free individuals were enrolled. Cell-free DNA integrity was calculated as the ratio of concentration of the longer ACTB (beta-actin) gene fragment to that of the shorter ACTB fragment, measured using quantitative PCR. Circulating nucleosomes were measured by an ELISA-based approach. We found that cfDNA integrity is higher in GC patients than in the control subjects (relative median values 0.51 vs. 0.38, respectively, P = .56) indicating prominent abundance of longer fragments in the patients. The patients with larger tumors (T3-4) had significantly higher cfDNA integrity than those with T1-T2 tumors. We also found GC patients to have higher concentrations of cNUCs in their plasma (relative median values 3.64 vs. 3.1). Importantly, the patients with high cfDNA integrity (i.e., lower fragmentation) had longer overall survival rates at 3 years than those with lower cfDNA integrity (76.5% vs. 38.9%, P = .02). Cell-free DNA fragmentation has a prognostic value. However, it has no diagnostic value in GC.