Value In Gastric Cancer Research Articles

LncRNA DRAIR is a novel prognostic and diagnostic biomarker for gastric cancer.

LncRNA diabetes regulated anti-inflammatory RNA (DRAIR) has been reported to be involved in diabetes-induced injury. However, its role in other human diseases is unclear. Our preliminary sequencing analysis showed its expression was altered in gastric cancer (GC). Thus, this study aimed to explore its diagnostic and prognostic values in GC. DRAIR expression in paired tumor and non-tumor tissues and plasma of GC patients and control samples was determined by RT-qPCR. The diagnostic value of DRAIR for early-stage GC was analyzed using ROC curve analysis. The prognostic value of DRAIR was explored by performing a follow-up (5-year) study. DRAIR expression was downregulated in GC tissues than in non-tumor tissues and in plasma of GC patients than in plasma of healthy controls. DRAIR expression in tumor tissues was closely and positively correlated with its expression in plasma. Plasma DRAIR effectively separated GC patients from controls. High DRAIR levels in tumor tissues and plasma samples were closely correlated with poor survival of GC patients. DRAIR is overexpressed in GC and may serve as an early diagnostic and prognostic biomarker for GC.

Clinical Value of Pepsinogen in the Screening, Prevention, and Diagnosis of Gastric Cancer

To compare the levels of serum pepsinogen (PG) in patients with gastric cancer (GC), patients with atrophic gastritis (AG), and healthy donors. Also, we explored the clinical value of PG detection for the diagnosis and treatment of GC. The PG level in peripheral blood from patients and heathy donors was determined using an Abbott automatic chemiluminescence instrument. The study included 117 patients with GC confirmed by gastroscopy and histopathology, of whom 13 patients had cancer at stage I, 47 at stage II, 41 at stage III, and 16 at stage IV. The AG group included 122 patients, and the control group had 120 healthy donors. The relationship between serum PG levels and the occurrence and development of GC, as well as the evaluation of the clinical value of diagnostic tests based on serum PG detection, were investigated by receiver operating characteristic (ROC) curve analyses. Pepsinogen I (PGI) levels gradually decreased from the control group, the AG group, and the GC group. PGI exhibited high diagnostic value for GC (area under the curve [AUC], 0.834; cutoff, 51.2 ng/mL, sensitivity, 81.7%; specificity, 68.4%), PGII (AUC, 0.587; cutoff value, 13.05 ng/mL; sensitivity, 65.8%; specificity, 53.8%), and PGR (AUC, 0.752; cutoff, 5.65; sensitivity, 54.2%; specificity, 87.2%). The occurrence of GC was negatively correlated with serum levels of PGI (B = -0.054; OR = 0.947; 95% confidence interval [CI], 0.925-0.970; P <.001) and PGR (B = -0.420; OR = 0.657; 95% CI, 0.499-0.864; P = .003). The combined detection of PGI, PGII, and PGR has important clinical value for the screening, prevention, and diagnosis of GC and could allow for earlier detection, diagnosis, and treatment of GC.

A Four-Gene-Based Risk Score With High Prognostic Value in Gastric Cancer.

BackgroundGastric adenocarcinoma is an important contributor to cancer mortality and morbidity. This study aimed to explore the prognostic value of mutation patterns in gastric adenocarcinoma.Materials and MethodsWe extracted somatic mutation data for 437 gastric adenocarcinoma samples from The Cancer Genome Atlas (TCGA) Stomach Adenocarcinoma (STAD) cohort. Kaplan–Meier survival in the R package maftools was used to analyze associations between mutations and survival. Multivariate Cox proportional model was used to establish risk formula. A four-gene-based risk score was developed to predict the overall survival of patients with gastric adenocarcinoma. We used the Tianjin cohort dataset with survival information to further evaluate the clinical value of this mutation signature.ResultsForty-five survival-related mutated genes were identified and verified, most of which were co-occurring in their mutation pattern and co-occurring with MLH3 and polymerase ϵ (POLE) mutations. Gastric adenocarcinoma samples with the 45 mutated genes had a significantly higher mutation count. Four-gene [UTRN, MUC16, coiled-coil domain-containing protein 178 (CCDC178), and HYDIN] mutation status was used to build a prognostic risk score that could be translated into the clinical setting. The association between the four-gene-based signature and overall survival remained statistically significant after controlling for age, sex, TNM stage, and POLE mutation status in the multivariate model [hazard ratio (HR), 1.88; 95% CI, 1.33–2.7; p < 0.001]. The prognostic significance of the four-gene-based risk score identified in TCGA cohort was validated in the Tianjin cohort.ConclusionA four-mutated gene risk formula was developed that correlated with the overall survival of patients with gastric adenocarcinoma using a multivariable Cox regression model. In two independent genomic datasets from TCGA and Tianjin cohorts, low risk scores were associated with higher tumor mutation loads and improved outcome in patients with gastric adenocarcinoma. This finding may have implications for prognostic prediction and therapeutic guidance for gastric adenocarcinoma.

The relationship of the tertiary lymphoid structures with the tumor-infiltrating lymphocytes and its prognostic value in gastric cancer.

To explore the relationship between the tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs), and their distribution characteristics as well as the prognostic value in gastric cancer (GC). The TLSs and four subtypes of TILs were assessed by immunohistochemical (IHC) staining. The presence of MECA-79 positive high endothelial venules (HEVs) identified among the ectopic lymphocyte aggregation area in the GC tissue was defined as valid TLSs. The number of labeled TILs was observed in 5 fields of the most positive cells in the tumor center, invasive edge and within the TLSs, at a field of vision ×40. The TLS distribution was significantly higher in the tumor invasive edge than the tumor center (p < 0.001). Similarly, the infiltrating density of CD8+ T cells and GrB+ T cells was statistically significantly higher in the tumor infiltrating edge than the tumor center. The total number of TILs and FOXP3+ T cells showed a contrary distribution. There was a positive correlation of the density of TLSs and TILs with both the location and the immune phenotype. A higher frequency of TILs and TLSs is often associated with favorable clinicopathologic parameters. Higher numbers of peri-TLSs (p = 0.007), peri-CD8+ (p = 0.019) and peri-GrB+TILs (p = 0.032) were significantly correlated with the favorable overall survival. Multivariate analysis revealed that the densities of TILs (p = 0.019) and TLSs (p = 0.037) were independent prognostic predictor for GC patients. We provide evidence that TLSs were positively associated with lymphocyte infiltration in GC. Thus, the formation of TLSs predicts advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients.

CircTMC5 promotes gastric cancer progression and metastasis by targeting miR-361-3p/RABL6.

Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC. CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC). CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC. CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.

Controlling Nutritional Status (CONUT) Score Is a Prognostic Factor for Patients with Gastric Cancer Treated by Perioperative FLOT.

The aim of this study was to show that the Controlling Nutritional Status (CONUT) score has predictive value in gastric cancer (GC) patients treated with perioperative fluorouracil, leucovorin, oxaliplatin, or docetaxel (FLOT). A total of 161 GC patients treated with perioperative FLOT in our center were included in the study. The ideal cutoff values for the CONUT score were obtained using the receiver operating characteristic (ROC) curve analysis, and the patients were divided into low (≤3) and high (> 3) CONUT groups. The associations of CONUT with clinicopathological factors and survival were evaluated retrospectively. The median follow-up time was 11.2 months (2.3-32.3 months). The median overall survival (OS) for the entire population was 14.7 months (95% CI 13.5-15.9 months). Median OS was not reached in the low-CONUT group, but it was 14.2 months (95% CI 12.6-15.9) in the high-CONUT group and the difference was statistically significant (p = 0.002). The univariate Cox proportional hazards model revealed that OS was significantly associated with Eastern Cooperative Oncology Group (ECOG) status (p < 0.001), T4b stage (p 0.03), modified Glasgow Prognostic Scores (mGPS) (p 0.005), prognostic index (PI) (p 0.011), prognostic nutritional index (PNI) (p < 0.001), CONUT score (p 0.003), and mucinous histology (p 0.004). In multivariate analysis, ECOG performance status (p 0.029), PNI (p 0.001), CONUT score (p 0.040), and mucinous histology (p 0.001) were still identified as independent prognostic factors for OS. Our study demonstrated the prognostic significance of the CONUT score in GC patients treated with perioperative FLOT.

Vitamin D modulation and microRNAs in gastric cancer: prognostic and therapeutic role.

Gastric adenocarcinoma arises after a complex interaction between the host and environmental factors. Tumor location and TNM are the tools that currently guide treatment decisions. Surgery is the only curative treatment, but relapse is common. After relapse or advanced staged disease survival is poor and systemic treatment has modestly improved survival. An association between sun exposure, vitamin D status and gastric cancer (GC) incidence and mortality has been reported. The molecular differences of the histological subtypes and the new molecular classifications account for the great heterogeneity of this disease and are the basis for the discovery of new therapeutic targets. New prognostic and predictive factors are essential and microRNAs (miRNAs) are endogenous small non-coding RNA molecules with a great potential for diagnosis, prognosis and treatment of cancer. There are hundreds of miRNAs with altered expression in tumor gastric tissue when compared to normal gastric tissue. Many of these miRNAs are associated with clinicopathological variables and survival in patients with GC. Furthermore, the expression of some of these miRNAs with prognostic importance in CG is influenced by vitamin D and others are mediators of some of the actions of this vitamin. This review aims to update the evidence on several miRNAs with prognostic value and therapeutic potential in GC, whose expression may be influenced by vitamin D or may regulate vitamin D signaling.

The Poor Prognosis of Patients with Stage III Gastric Cancer after D2 Dissection Is Mainly due to Lymphatic Metastasis, Especially the Metastasis of No.12a LN: A Nested Case-Control Study

Background: The prognosis of stage III gastric cancer (GC) patients based on the 8th edition TNM staging system after D2 dissection was still heterogeneous. We aimed to explore clinicopathological reasons that led to the poor prognosis of these patients, especially from a surgical aspect. Methods: We divided 320 stage III GC patients who underwent distal or total gastrectomy with D2 lymphadenectomy into group 1 and group 2, according to the disease-free survival (DFS), and compared the clinicopathological features between these 2 groups. Then, we divided group 1 into group 1D and group 1T and group 2 into group 2D and group 2T, according to distal or total gastrectomy. Finally, we compared the status of lymph node (LN) metastasis in each group of perigastric LN between the subgroups, respectively. Results: Univariate analyses revealed that patients’ LN metastasis was the only significant difference between group 1 and group 2 (p < 0.05). Compared with group 1D, the percentage of patients who had metastatic LN in all groups of the perigastric LN (included No.1, 3, 4sb, 4d, 5, 6, 7, 8a, 9, 11p and 12a) increased in group 2D. A similar tendency was found in group 2T (included No.1, 2, 3, 4sa, 4sb, 4d, 5, 6, 7, 8a, 9, 10, 11p, 11d and 12a) compared with group 1T. Further multivariate regression analyses revealed that the increases of group No.12a and 5 LN were significant (p < 0.05) in group 2D, the increases of group No.12a, 8a and 6 LN were significant (p < 0.05) in group 2T, respectively. Among these, the increases of group No.12a LNs were the most significant (p < 0.01). Conclusions: The poor prognosis of patients with stage III GC after D2 dissection is mainly due to lymphatic metastasis. The status of LN metastasis in the prognostic value of GC needs to be further enhanced in present staging systems. Maybe the metastasis of No.12a LN is the most significant poor prognostic factor of these patients. It points out that the dissection of No.12a LN should be carefully performed in radical gastrectomy.

Identification and Validation of SNP-Containing Genes With Prognostic Value in Gastric Cancer via Integrated Bioinformatics Analysis.

BackgroundGastric cancer is one of the most common malignancies worldwide. Although the diagnosis and treatment of this disease have substantially improved in recent years, the five-year survival rate of gastric cancer is still low due to local recurrence and distant metastasis. An in-depth study of the molecular pathogenesis of gastric cancer and related prognostic markers will help improve the quality of life and prognosis of patients with this disease. The purpose of this study was to identify and verify key SNPs in genes with prognostic value for gastric cancer.MethodsSNP-related data from gastric cancer patients were obtained from The Cancer Genome Atlas (TCGA) database, and the functions and pathways of the mutated genes were analyzed using DAVID software. A protein-protein interaction (PPI) network was constructed using the STRING database and visualized by Cytoscape software, and molecular complex detection (MCODE) was used to screen the PPI network to extract important mutated genes. Ten hub genes were identified using cytoHubba, and the expression levels and the prognostic value of the central genes were determined by UALCAN and Kaplan-Meier Plotter. Finally, quantitative PCR and Western blotting were used to verify the expression of the hub genes in gastric cancer cells.ResultsFrom the database, 945 genes with mutations in more than 25 samples were identified. The PPI network had 360 nodes and 1616 edges. Finally, cytoHubba identified six key genes (TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4), and their expression levels were closely related to the survival rate of gastric cancer patients.ConclusionOur results indicate that TP53, HRAS, BRCA1, PIK3CA, AKT1, and SMARCA4 may be key genes for the development and prognosis of gastric cancer. Our research provides an important bioinformatics foundation and related theoretical foundation for further exploring the molecular pathogenesis of gastric cancer and evaluating the prognosis of patients.

Comprehensive analysis of the prognostic value of the chemokine-like factor-like MARVEL transmembrane domain-containing family in gastric cancer.

The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family refers to a family of transcriptional repressor genes. CMTMs are closely associated with the epigenetic regulatory mechanisms and development of multiple malignancies, including gastric cancer. However, their specific biological functions and prognostic values in gastric cancer have yet to be elucidated. Tumor sample datasets were retrieved and analyzed using databases including Oncomine, STRING, GEPIA2, cBioportal, and Kaplan-Meier plotter. To investigate the prognostic role of CMTMs in gastric cancer, we applied unsupervised hierarchical clustering analysis of CMTM gene expression patterns. While the mRNA levels of CMTM1/3/6/7/8 were upregulated in gastric cancer, CMTM2/4/5 showed no statistically significant difference at the mRNA level in patients with gastric cancer. Moreover, the mRNA expressions of different CMTMs exhibited strong correlations with various clinical parameters of patients with gastric cancer, including tumor stage, metastatic lymph node status, H. pylori status, and tumor grade. Also, the results suggested that elevated levels of CMTM3/5 mRNA had a significant association (P<0.05) with poor overall survival, progression-free survival, and post-progression survival. Conversely, elevated expression of CMTM2/4/6 mRNA had a significant association with better overall survival, progression-free survival, and post-progression survival. Unsupervised hierarchical clustering analysis successfully identified 2 major clusters of patients as follows: signature #1: CMTM4/6/8 and signature #2: CMTM1/2/3/5/7. Signature #2 was closely correlated with poorer overall survival, which indicated that the expression pattern of the CMTM family could be a novel prognostic factor for patients with gastric cancer. These results suggest that the expression levels of CMTM genes possibly have prognostic value as a biomarker of gastric cancer.

Cholinesterase is Associated With Prognosis and Response to Chemotherapy in Advanced Gastric Cancer.

Background: Cholinesterase (CHE) is a routine serum biomarker in gastric cancer (GC). However, little research has been done on its clinical value in advanced GC. In addition, it is not clear whether it can be used as biomarker for the response and prognosis of advanced GC patients. Methods: Between Jan. 2013 and Dec. 2016, a total of 150 patients with advanced GC treated with first-line chemotherapy were admitted to Changzhou Tumor Hospital Affiliated to Soochow University. We retrospectively identified serum CHE level on the day before chemotherapy and at the end of chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between serum CHE levels and progression-free survival (PFS) and overall survival (OS). Results: A total of 150 advanced GC patients were included and divided into serum level ≥5,000 IU/L and serum level <5,000 IU/L. CHE level lower than 5,000 IU/L was associated with poorer PFS (HR, 1.60; 95% CI, 1.141–2.243; p = 0.006), poorer OS (HR, 1.76; 95% CI, 1.228–2.515; p = 0.002) and trend of poorer response (HR, 0.56; 95% CI, 0.272–1.129; p = 0.104). In univariate and multivariate logistic regression analysis, only liver metastasis and PS score were significantly associated with objective response (p < 0.05). The medium PFS was 8.0 months in patients with post-treatment CHE increased vs. 3.8 months in patients with CHE decreased after chemotherapy (HR, 1.82; 95% CI 1.28–2.57; p = 0.0002). The medium OS was 13.1 months in patients with increased post-treatment CHE vs. 8.1 months in patients with decreased post-treatment CHE (HR, 1.87; 95% CI 1.29–2.71; p = 0.0002). Conclusion: Advanced GC with CHE levels below 5,000 IU/L was significantly associated with poor PFS and OS. The results suggested that CHE analysis before chemotherapy was a promising prognostic marker for advanced GC.

High Expression of Interleukin-2 Receptor Subunit Gamma Reveals Poor Prognosis in Human Gastric Cancer.

Precision medicine for gastric cancer (GC) is still an unsolved issue, because most available target drugs are not specifically designed for GC. Exploring novel signaling molecules with target value for GC is in urgent need. This study aimed to reveal that interleukin-2 receptor subunit gamma (IL2RG) is such a key molecule in human GC progression. GC tissues and paracancerous gastric tissues were collected from 7 patients (5 males and 2 females) during tumor radical excision surgery. These tissues were used to identify the differentially expressed genes (DEGs) with RNA-seq and serial bioinformatics analyses including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene expression profiling interactive analysis (GEPIA), and survival analysis. RT-qPCR and western blotting were performed to compare the mRNA and protein expression levels of IL2RG between GC tissues and adjacent normal gastric tissues as well as between GC cell line SGC-7901 and normal gastric epithelial cell line GES-1. Results showed striking elevations of IL2RG both in the mRNA and protein levels in GC tissues and human gastric cancer SGC-7901 cell line compared, respectively, with the adjacent normal gastric tissues and normal GES-1 cells, and higher IL2RG expression was associated with lower survival. Analyses on the GSE29272 and GSE15459 datasets from Gene Expression Omnibus verified that IL2RG was highly expressed in GC patients and was associated with poor overall survival. In addition, molecular docking showed that a small molecule, resatorvid (TAK 242), might be an inhibitor of IL2RG. We conclude that IL2RG is overexpressed in advanced GC and is associated with low survival. IL2RG may serve as a biomarker of GC progression and poor prognosis.

Immune Cell Landscape in Gastric Cancer.

Background The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t-test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients' clinical characteristics was assessed by univariate analysis. Results In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients' prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients' gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

Clinical significance and prognostic value of C-reactive protein/albumin ratio in gastric cancer.

PurposeThis study was aimed to evaluate the clinical significance and prognostic value of CRP/albumin ratio (CAR) in patients with gastric cancer.MethodsThe data of 205 gastric cancer patients who underwent surgery was analyzed retrospectively. The association of CAR with the clinical features and prognostic value in gastric cancer was analyzed. The data of this study was combined with previous studies to further determine the prognostic value of CAR in patients with gastric cancer using a meta-analysis method.ResultsCox analysis revealed that preoperative CAR was an independent prognosis indicator in patients with gastric cancer. High expression of CAR indicated a shorter survival time than in those with lower expression. CAR has a higher prognostic value in the 1-, 3-, and 5-year overall survival in patients with gastric cancer. CAR showed significant difference regarding the gastric cancer patients' age, M stage, and clinical stage. The discriminate value of CAR in M stage of gastric cancer was high (area under the curve, 0.809). A meta-analysis combining previous data and our data showed that preoperative CAR demonstrated a significant association with the overall survival of patients with gastric cancer.ConclusionThis study demonstrated that preoperative CAR could serve as an important prognostic indicator in patients with gastric cancer.

Comprehensive Analysis of Ferroptosis-Related Markers for the Clinical and Biological Value in Gastric Cancer.

Gastric cancer is a highly malignant tumor with poor survival rate. Ferroptosis, a newly defined regulated cell death, is closely related to several tumors. Introduction of ferroptosis is promising for cancer treatments. However, the predictive role of ferroptosis in GC remains elusive. In this study, we screened the ferroptosis-related genes which were differentially expressed between normal and GC tissues. Then, based on these differentially expressed genes (DEGs), the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were applied to construct the 10-gene prognostic signature (SP1, MYB, ALDH3A2, KEAP1, AIFM2, ITGB4, TGFBR1, MAP1LC3B, NOX4, and ZFP36) in TCGA training dataset. Based on the median risk score, all GC patients in TCGA training dataset and GSE84437 testing dataset were classified into a high- or low-risk group. GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001). Combined with the clinical characteristics, the risk score was proven as an independent factor for predicting the OS of GC patients. Besides, the GC patients in the high- or low-risk group showed significantly different GO and KEGG functional enrichments, somatic mutation, fractions of immune cells, and immunotherapy response. Then, the expression levels of these genes in signature were further verified in the GC cell lines and our own GC samples (30-paired tumor/normal tissues). Furthermore, the effects of ferroptosis inducer Erastin on these 10 ferroptosis-related genes in GC cell lines were also explored in our study. In conclusion, our study constructed a prognostic signature of 10 ferroptosis-related genes, which could well predict the prognosis and immunotherapy for GC patients.

Prognostic Role of Red Distribution Width (RDW) Value in Gastric Cancer

To investigate the prognostic effect of red distribution width (RDW) in patients with gastric cancer. Observational study. Department of Surgical Oncology, Ankara University School of Medicine, between November 2010 and January 2020. Patients diagnosed with adenocarcinoma by biopsy, who underwent radical surgery and lymph node dissection, and had preoperative RDW value, were inducted. Patients who had history of active inflammation in the past three months, received treatment for hematology disorder, blood transfusion, malignancy other than gastric cancer, autoimmune disease, venous thrombosis, or under 18 years of age, and those having cardiac and cerebrovascular diseases and distant metastases were excluded from the study. Apart from diagnosis, preoperative blood values, clinicopathologial, demographic features, and follow-up data were included in the study. RDW average value was 15.11 ± 2.87 and median value was 14.3%. For RDW cut off value, 13.4% was accepted as reference from previous studies was divided into two groups as <13.4% and ≥13.4%. While it was <13.4% in 119 patients; in 292 patients, it was "≥13.4%". High RDW value showed poor survival (p<0.001). RDW, the current hematological marker, can be used as an important indicator for monitoring the progression and prognosis of gastric cancer. Key Words: Gastrectomy, Gastric cancer, Laparoscopy, Surgical oncology, Red distribution width, survival.

Highly expressed IFITM10 is associated with early diagnosis and T stage of gastric cancer.

BackgroundInterferon-induced transmembrane proteins (IFITMs) are a family of proteins which functions mainly include controlling cell proliferation, promoting homotypic cell adhesion, and preventing viral infection. This research study attempts to elucidate the association between IFITM10 expression level and gastric cancer (GC).MethodsTranscriptome sequencing and clinical information on GC and normal tissues was obtained from the Cancer Genome Atlas (TCGA) database. R and related statistical packages were used to analyze the relationship between IFITM10 and survival in GC patients based on available clinical information. Receiver operating characteristic curves (ROC) were constructed using the SPSS software package. IFITM10 expression levels in patients tissue samples were examined by qPCR and association between IFITM10 expression and clinic characteristics was analyzed using SPSS. The signaling pathway associated with IFITM10 was analyzed using gene set enrichment analysis (GSEA).ResultsIn the TCGA database, IFITM10 was highly expressed in GC tissues (P<0.001). Area under the curve (AUC) value for IFITM10 in all samples was 0.813, while AUC value in the paired GC and adjacent tissues was 0.955. In the sample of surgical patients, IFITM10 was highly expressed in GC tissues (P<0.001). IFITM10 expression was higher in T1 and T2 tissues (P=0.042), male patients (P=0.031), and tissues without neuro infiltration (P=0.008).ConclusionsIFITM10 is highly expressed in GC and can serve as an early diagnostic indicator. High expression of IFITM10 was related to a low T stage in GC.

Screening of Potential Biomarkers for Gastric Cancer with Diagnostic Value Using Label-free Global Proteome Analysis

Gastric cancer (GC) is known as a top malignant type of tumors worldwide. Despite the recent decrease in mortality rates, the prognosis remains poor. Therefore, it is necessary to find novel biomarkers with early diagnostic value for GC. In this study, we present a large-scale proteomic analysis of 30 GC tissues and 30 matched healthy tissues using label-free global proteome profiling. Our results identified 537 differentially expressed proteins, including 280 upregulated and 257 downregulated proteins. The ingenuity pathway analysis (IPA) results indicated that the sirtuin signaling pathway was the most activated pathway in GC tissues whereas oxidative phosphorylation was the most inhibited. Moreover, the most activated molecular function was cellular movement, including tissue invasion by tumor cell lines. Based on IPA results, 15 hub proteins were screened. Using the receiver operating characteristic curve, most of hub proteins showed a high diagnostic power in distinguishing between tumors and healthy controls. A four-protein (ATP5B-ATP5O-NDUFB4-NDUFB8) diagnostic signature was built using a random forest model. The area under the curve (AUC) values of this model were 0.996 and 0.886 for the training and testing sets, respectively, suggesting that the four-protein signature has a high diagnostic power. This signature was further tested with independent datasets using plasma enzyme-linked immune sorbent assays, resulting in an AUC value of 0.778 for distinguishing GC tissues from healthy controls, and using immunohistochemical tissue microarray analysis, resulting in an AUC value of 0.805. In conclusion, this study identifies potential biomarkers and improves our understanding of the pathogenesis, providing novel therapeutic targets for GC.

H19 Rises in Gastric Cancer and Exerts a Tumor-Promoting Function via miR-138/E2F2 Axis.

PurposeThe aim of this paper was to investigate H19 expression in gastric cancer (GC) and its effects on the biological behavior of gastric cancer cells (GCCs), and at exploring its potential mechanism.MethodsH19 expression in the patients’ tissues and serum was detected, and the correlation of the expression with the patients’ pathological data and survival rate was analyzed. Overexpression or inhibitory vectors of H19, microRNA-138 (miR-138) and E2F2 were constructed and transfected into GCCs to observe their effects on the cells’ proliferation, invasion and apoptosis.ResultsH19 rose in GC and was higher in GC patients with a tumor size ≥5 cm, high stages (III+IV) and lymph node metastasis. High H19 expression was associated with the poorer survival rate of the patients, so serum H19 had a certain diagnostic value for GC. H19 knockdown could inhibit GCCs to proliferate and invade and induce their apoptosis. miR-138 can be used as the target gene of H19, and E2F2 can be negatively regulated by this miR, so miR-138 knockdown or E2F2 upregulation can weaken GCCs’ biological behavior changes that were caused by H19 knockdown.ConclusionH19 can be used as a biological indicator for diagnosing GC and predicting patients’ poor prognosis. Additionally, it promotes GCCs to proliferate and invade through miR-138/E2F2 axis.

Diagnostic and prognostic value of plasma heat shock protein 90alpha in gastric cancer

BackgroundThe role of plasma heat shock protein 90alpha (Hsp90α) in gastric cancers remains unclear. This study aimed to clarify the diagnostic and prognostic value of plasma Hsp90α in gastric cancer. MethodsData regarding 976 gastric cancer, 50 gastric inflammatory diseases, and 100 healthy controls were collected. Plasma Hsp90α levels in gastric cancer were compared to those in controls. Its correlation with tumor biomarkers and immune cells was examined. The association of plasma Hsp90α with clinical features and the diagnostic and prognostic value in gastric cancer were also determined. ResultsPlasma Hsp90α levels were remarkably increased in gastric cancer, compared to those in gastric inflammatory diseases and healthy controls. Moreover, plasma Hsp90α was correlated with CEA, CA125, CA153, CA199, T cells, Th/Ts ratio, and B cells. Plasma Hsp90α was also associated with the metastasis stage. Multivariate logistic regression analysis revealed that Hsp90α, B cells, and T cells were significantly associated with gastric cancer. Plasma Hsp90α has a moderate diagnostic value, which increased when combined with B cell, T cells. Finally, plasma Hsp90α was not associated with the survival of gastric cancer patients. ConclusionPlasma Hsp90α was elevated in gastric cancer and correlated with tumor biomarkers and immune cells. Plasma Hsp90α was associated with the metastasis stage and had moderate diagnostic performance but little prognostic value in gastric cancer.