Expression In Gastric Carcinoma Research Articles

Spectrum of Gastric Carcinoma in a Tertiary Care Centre with Special Reference to PDL1 and Cyciln D1

Introduction: Gastric carcinoma is the fifth most frequently diagnosed tumor and the fourth leading cause of death. They represent a heterogenous group of tumors with multifactorial etiologies, both environmental and genetic. PD-L1 is a transmembrane protein, and a positive PD-L1 expression in gastric carcinoma may be a predictive biomarker of the response to PD-1/PD-L1 immune checkpoint inhibitors. Cyclin D1 is an important cell cycle regulatory protein and involved in the carcinogenesis of various cancers including gastric cancer. Aims: The aim of this study is to find out the clinicopathological spectrum of gastric carcinoma and to show the immunohistochemical expression of Cyclin D1 and PD-L1 to evaluate their prognostic importance and their therapeutic impact. Study Design: It is an observational cross-sectional study conducted in the Department of Pathology in collaboration with the Department of Surgery, in a tertiary care hospital. Partial and total gastrectomies were selected from January 2021 to July 2022 in a tertiary care hospital. Clinical history was collected in the study proforma. Immunohistochemical staining for Cyclin D1 and PD-L1 was performed. Material and Methods: The clinicopathological parameters like age, gender, histological type, regional lymph node status, lymphovascular invasion, perineural invasion, and pathological stage were compared and correlated with Cyclin D1 and PD-L1 expression. Results: Positive Cyclin D1 and PDL1 expression were found in 50% and 70% cases of gastric carcinoma, respectively. Cyclin D1 expression showed statistically significant correlation with anemia, regional lymph node status, and lymphovascular invasion. PD-L1 and Cyclin D1 expression showed statistically significant association between them (p value-0.0006). Conclusion: Cyclin D1 and PDL1 are important biomarkers in gastric carcinoma. Their contribution towards prediction of progression and prognosis, along with newer therapeutic modalities, is of immense importace in these patients. A statistically significant correlation was found between these two markers.

Clinicopathological Correlation of P53 Protein Expression in different Histological Subtypes of Gastric Carcinoma

Introduction: Gastric cancer is one of the common cancers after lung cancer worldwide, especially in the developing countries. p53 immunohistochemical expression has been proposed as a potential tool to evaluate the biological behavior of gastric cancer. However, its practical implication in gastric cancer prognosis or treatment by restoration of mutated p53 function is yet to be fully exploited. Hence, this study with the aim of assessing the yield of p53 expression in gastric carcinoma and its relationship with various clinicopathological parameters was formulated. Objectives: To assess immunohistochemical expression of p53 protein in different histological subtypes of gastric carcinoma cases and to study correlation between p53 protein expression and different clinicopathological parameters like age, gender, tumour location, gross pattern, histological types, degree of tumor differentiation and pathological staging in the above said cases. Materials and Methods: This was a hospital based cross-sectional study done over a period of 18 months on 60 cases of gastrectomies with proven histological diagnosis of gastric carcinoma. Observation and Results: Strong p53 expression was frequent among elderly male patients (>60 years) who had ulceroproliferative tumors, located at pyloric antrum belonging to pTNM stage IIIA. In 87% cases, it was expressed, predominantly in moderately differentiated intestinal type with serosal invasion. Also, cases even with no lymph node metastasis showed p53 expression. Conclusion: Few findings were contradictory to other similar studies e.g. lymph node negative cases showing P53 expression does not support the hypothesis of predicting lymph node status by p53 expression. No significant correlation between p53 expression and different clinicopathological parameters in gastric carcinoma cases was seen. Keywords: P53, immunohistochemical, clinicopathological, histological subtypes, metastasis

MiR-122-IGF-1R signaling allied through the dysregulated lncRNA MALAT-1 expression in gastric carcinoma

MALAT-1 is extremely elevated in human malignancies thus functions as a prognostic biomarker. Nevertheless, limited data has been discovered concerning MALAT's contribution in stomach cancer. MALAT-1 expression appeared considerably greater in gastric cancer (GC) rats with remote miR-122-IGF-1R impact. MALAT-1 depletion inhibited cell cycle development, cell division and invasion, thus boosting death of GC cells. Likewise, miR-122-IGF-1R expression was linked to MALAT-1 deregulations in GC. Biological markers discovery based on biochemical data alongside detailed genome study might enhance prognosis, diagnosis and therapeutic compliance. This article summed up the most recent developments and techniques in GC biomarkers and may have applications for early detection, precise estimation of treatment strategies, and future perspectives according to molecular classification and profiling. In rats, GC was induced by 20-MCA, followed by DOX, Liposomal DOX, and PEGylated-Dox treatment. In addition to histopathological examinations, GC tumor biomarkers such as CEA, CA12–5, KRAS, AKT, PTEN, TP53, JAK-2, lnc- MALAT-1 and miR-122-IGF-1R were tracked. These findings reveal that MALAT-1 may be oncogenic in GC. Prominent MALAT-1 levels may assist as an indicator of metastasis in GC, and that miR-122-IGF-1R expression is associated via reduced MALAT-1 signaling. Finally, PEG-DOX may be an excellent option for GC therapy.

The association and clinicopathological significance of Integrin alphavbeta6 and Rac1 expression in gastric carcinoma.

The present study investigate the expression and correlation of ITGB6 and Rac1 proteins in gastric cancer tissues. By exploring the clinical significance and functions of these proteins, we aimed to gain further insights into the mechanisms underlying gastric cancer development. In this study, a total of 198 patients diagnosed with gastric cancer and who underwent gastrectomy between July 2010 to October 2012 were included. The median follow-up time was 52.00 months. To evaluate the factors influencing overall survival, Kaplan-Meier survival curve analysis and Cox regression analysis were conducted. Furthermore, an independent prognostic factor-based nomogram was constructed and validated to predict survival outcomes in gastric cancer patients. In addition, in vitro experiments including CCK8 and Transwell assays were conducted to explore the roles of ITGB6 and Rac1 in gastric cancer. The expression levels of ITGB6 and Rac1 in gastric cancerous and paraneoplastic tissues were detected by immunohistochemistry. The correlation and clinical significance of the two proteins were also investigated. ITGB6 expression showed significant associations with tumor size (P=0.030), pathological grading (P=0.013), location (P=0.031), N stage (P=0.002), and clinical stage (P=0.002). Additionally, we found that tumor size (P=0.013), tumor's anatomical location (P=0.031), N stage (P=0.002), clinical stage (P=0.035), and survival status (P<0.001) were significantly associated with the expression of Rac1. ITGB6 was moderately correlated with Rac1 (r=0.285, P<0.001). Both the Kaplan-Meier survival analysis and Cox regression model analysis demonstrated that the presence of positive expression of ITGB6 and Rac1 proteins served as independent prognostic factors for gastric cancer. These findings highlight the potential of ITGB6 and Rac1 as valuable markers for predicting the prognosis of gastric cancer patients (HR=2.212 P<0.001 and HR=2.073 P=0.001), with a significant poorer trend for 5-year survival (P<0.0001, respectively, the log-rank test). Additionally, subsequent in vitro experiments preliminarily demonstrated that ITGB6 and Rac1 promoted the proliferation, migration and invasion of gastric cancer cells, and ITGB6 may functions via targeting Rac1. ITGB6 and Rac1 are indicators of poor prognosis and tumor progression in gastric cancer patients. The potential signaling pathways associated with both may provide useful targets for the prevention and treatment of gastric cancer.

Comparative analysis of ARID1A mutations with mRNA levels and protein expression in gastric carcinoma

The ARID1A gene is pivotal in chromatin remodeling and genomic integrity and is frequently mutated in various cancer types. ARID1A mutation is the second most frequently mutated tumor suppressor gene and has been suggested as a predictor of immunotherapeutic responsiveness in gastric carcinoma (GC). Despite its significance, the relationship among ARID1A somatic mutations, RNA expression levels, and protein expression remains unclear, particularly in GC. For this purpose, we performed comparative study in two cohorts. Cohort 1 used next-generation sequencing (NGS) to identify 112 GC cases with ARID1A mutations. These cases were compared with ARID1A immunohistochemistry (IHC) results. Cohort 2 employed microarray gene expression data to assess ARID1A RNA levels and compare them with ARID1A IHC results. In Cohort 1, 38.4% of ARID1A-mutated GC exhibited a complete loss of ARID1A protein when assessed by IHC, whereas the remaining 61.6% displayed intact ARID1A. Discordance between NGS and IHC results was not associated with specific mutation sites, variant classifications, or variant allele frequencies. In Cohort 2, 24.1% of the patients demonstrated a loss of ARID1A protein, and there was no significant difference in mRNA levels between the ARID1A protein-intact and -loss groups. Our study revealed a substantial discrepancy between ARID1A mutations detected using NGS and protein expression assessed using IHC in GC. Moreover, ARID1A mRNA expression levels did not correlate well with protein expression. These findings highlighted the complexity of ARID1A expression in GC.

Elevated expression of Axin2 in intestinal metaplasia and gastric cancers.

The Wnt signaling pathway regulates crucial cellular processes, including stem cell development and tissue repair. Dysregulation of this pathway, particularly β-catenin stabilization, is linked to colorectal carcinoma and other tumors. Axin2, a critical component in the pathway, plays a role in β-catenin regulation. This study examines Axin2 expression in normal gastric mucosa and various gastric pathologies. Formalin-fixed and paraffin-embedded tissue samples from normal stomach, gastritis, intestinal metaplasia (IM), and gastric carcinoma were collected. Axin2 and β-catenin expression were evaluated using RNA in situ hybridization and immunohistochemistry, respectively. Histo-scores (H-scores) were calculated to quantify expression levels of Axin2. Associations between Axin2 expression and clinicopathological variables were examined. Axin2 expression was examined in normal stomach, gastritis, and IM tissues. Axin2 expression was mainly observed in the surface and isthmus areas in the normal stomach and gastritis, whereas Axin2 expression was markedly higher at the bases of IM. Axin2 H-scores were significantly elevated in IM (mean ± standard deviation [SD], 87.0 ± 38.9) compared to normal (mean ± SD, 18.0 ± 4.5) and gastritis tissues (mean ± SD, 33.0 ± 18.6). In total, 30% of gastric carcinomas showed higher Axin2 expression. Axin2 expression did not have significant associations with age, sex, Lauren classification, histological differentiation, invasion depth, and lymph node metastasis. However, a strong positive correlation was observed between Axin2 and nuclear β-catenin in gastric carcinomas (p < .001). Axin2 expression was significantly increased in IM compared to normal and gastritis cases. In addition, Axin2 showed a strong positive association with nuclear β-catenin expression in gastric carcinomas, demonstrating a close relationship with abnormal Wnt/β-catenin signaling pathway.

E-cadherin expression – Significance in gastric carcinoma

Gastric carcinoma is aggressive cancer with poor prognosis. E-cadherin is 120 kD calcium mediated transmembrane glycoprotein that forms the cell adhesion molecule which maintains the integrity of epithelial cells by keeping it cohesive. E-cadherin down regulation in gastric cancer is of great significance in the dissociation of epithelial cells, alteration of tumor microenvironment, invasion, tumor genesis and metastasis. To study the E-cadherin expression in gastric carcinoma and to correlate with the existing clinical and pathological parameters.The study included 100 confirmed cases of adenocarcinoma from gastrectomy specimens. Immunostaining was done with E-cadherin mouse monoclonal antibody and expression studied based on the staining pattern and correlated with various clinico-pathological parameters. Data was statistically analysed by chi square test with calculation of p-value.E-cadherin expression showed aberrant staining in 87% cases. E-cadherin expression showed significant correlation with histological types, tumor grade, tumor depth of invasion, lymphovascular invasion and lymphnode involvement. The expression E-cadherin in gastric cancer was aberrant in 100 % of diffuse type and poorly differentiated tumors. 96.61% of lymph node positive cases showed aberrant expression. The cases with aberrant expression were comparatively more in T3 (100%) and T4 (93.75%) tumors.The study highlights the significance of E-cadherin expression in gastric carcinoma that can be utilised as a potent bio marker for aggressiveness, metastasis and prognosis.

Transcriptomic analysis reveals the promotion of lymph node metastasis by Helicobacter pylori infection via upregulating chemokine (C-X-C motif) receptor 2 expression in gastric carcinoma

Gastric carcinoma (GC) progression is mainly caused by local aggression and lymph node metastasis. However, some patients with early T-stage disease have lymph node metastasis, whereas some patients with late T-stage disease do not have lymph node metastasis, which indicates that invasion and metastasis are not always sequential in some GC patients. In the present study, the data of 101 GC cases were acquired from TCGA and divided into T-late-N-negative and T-early-N-positive groups according to pathological stages. A total of 338 genes were identified as differential genes between the T-late-N-negative and T-early-N-positive groups. GSEA showed that epithelial cell signaling in the Helicobacter pylori (HP) infection pathway was enriched in the T-early-N-positive group. MB staining indicated that the HP infection rate was 63% (39/62) in N-positive patients compared to 42% (16/38) in N-negative patients. To investigate the potential mechanism, we focused on the gene chemokine (C-X-C motif) receptor 2 (CXCR2), which was not only clustered in the gene set of epithelial cells signaling in the HP infection pathway but also significantly upregulated in T-early-N-positive GC by the analysis of the different genes based on the TCGA dataset. A meta-analysis showed that CXCR2 expression was positively correlated with N-stage but not with T-stage in GC. This study indicated that invasion and metastasis could be independent processes driven by different molecular mechanisms in some GC patients. HP infection was a potential factor that promoted lymph node metastasis by upregulating CXCR2 expression.

CDX2 and Ki-67 Expression in Gastric Carcinoma and Its Association with Clinocopathological Parameters

Background: CDX2 has been established as a good prognostic marker for colorectal carcinomas. Differentiated adenocarcinomas are characterized by higher CDX2 expression than undifferentiated tumors with stronger reactivity in intestinal phenotypes. There is a close correlation between the degree of tumor differentiation and the Ki-67 score. It was also observed that strong CDX2 expression was associated with low Ki-67 index whereas negative or dim CDX2 expression was associated with high Ki-67 index. Methods: Gastric biopsies and gastrectomy specimens with gastric carcinoma were evaluated clinicopathologically and processed for immunohistochemistry (IHC) staining to assess CDX2 and Ki-67 expression. The relationship between 2 markers and each clinicopathological parameter was evaluated. Data was statistically analysed. P&lt;0.05 were taken for statistical significance. Results: The study was done on 57 gastric adenocarcinoma cases with mean age 56.12 years. No significant correlation was found between CDX2 &amp; Ki-67 with clinical, gross &amp; microscopic parameters except for tumor location and depth of invasion. Significant correlation was detected between CDX2 (p=0.04) &amp; Ki-67 (p=0.03) with tumor location. Depth of tumor invasion was significantly associated with Ki-67 (p=0.013). No significant association between CDX2 and Ki-67 was observed. Conclusion: The statistical correlation between CDX2 &amp; Ki-67 with clinicopathological parameters proves that CDX2 &amp; Ki-67 to be the independent markers with respect to tumor site and depth of invasion (in case of Ki-67). But due to lack of association of CDX2 with Ki-67 further studies need to be done with higher sample size.

HER2 protein expression correlates with Lauren classification and P53 in gastric cancer patients.

Human epidermal growth factor receptor 2 (HER2) is a key pathological characteristic of gastric cancer (GC). However, the clinical significance of HER2 expression in gastric carcinoma remains controversial. The purpose of this study was to analyze the clinicopathological characteristics of HER2 protein expression, Lauren classification and tumor protein p53 (P53) expression and to evaluate the clinical significance of HER2 protein expression. A total of 176 consecutive patients were prospectively recruited between January 2014 and December 2016 at the Second Affiliated Hospital of Zhejiang University School of Medicine. Histological analysis of the resected tissue was performed for HER2 protein expression using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Additionally, the expression status of HER2 protein and clinicopathological features were analyzed using the chi-squared (χ2) test. Survival analysis was performed using the Kaplan–Meier method, and differences between the survival curves were determined using the log-rank test. All statistical analyses were conducted using SPSS 22.0 statistical software program (IBM Corp., Armonk, NY). A total of 176 patients with GC were enrolled in this study. Intratumoral heterogeneity of HER2 protein overexpression was observed in 42 of 176 cases with IHC grade 2+, accompanied by FISH positivity and IHC grade 3+. HER2 protein expression was correlated with tumor differentiation (P < .001), Lauren classification (P = .001), Borrmann type (P = .003) and P53 expression (P < .001). HER2 protein positivity was associated with significantly higher overall survival (OS) (P = .038). Overexpression of HER2 protein was observed in 23.9% of the cases and was significantly related to the Lauren intestinal subtype and P53 negative expression. HER2 protein overexpression was independently associated with higher OS.

PD-L1 expression in gastric carcinoma – a biomarker for immunotherapy

Introduction and Aim: Immunotherapy is now being widely used for targeted therapy in several cancers. The PD-1/ PD-L1 (programmed cell death receptor/programmed cell death ligand) axis inhibits the expansion of tumour specific T cells and prevents the immune response against tumours. PD-L1 expression is seen in many cancers including gastric carcinomas and anti PDL1 antibodies are being used to produce tumour regression. This study was done to evaluate PD-L1 expression in gastric carcinomas and correlate this with the different histological types, grades and stages of these tumours Materials and Methods: In this study, 50 cases of gastric adenocarcinoma were analysed for PD-L1 expression using immunohistochemistry. PD-L1 expression was correlated with histopathological factors including histological type, differentiation, grade and stage using statistical methods. Results: A positive PD-L1 expression was observed in 52% of the cases. A positive correlation between PD-L1 positivity and tumour depth to which the tumour was invading the stomach was observed. No correlation was noted with expression of PD-L1 and histological type, differentiation, histological grade and presence/absence of nodal metastasis. Conclusion: PD-L1 expression was seen in more than half of the patients in our study. Hence it is suggested that anti PD-L1 inhibitors can be used as an adjunct in the treatment of gastric cancers, especially those with a greater depth of invasion.

Silencing of Nudix type 5 represses proliferation and invasion and enhances chemosensitivity of gastric carcinoma cells by affecting the AKT/GSK-3β/β-catenin pathway

Nudix type 5 (NUDT5) has been recently identified as a new cancer-associated protein that is involved in numerous cancers. To date, the relationship between NUDT5 and gastric carcinoma has not been addressed. In the current research, we focused on exploring the potential relevance of NUDT5 in gastric carcinoma. The initial analysis of NUDT5 expression in gastric carcinoma by TCGA data revealed a clear increase in NUDT5 expression in tumor versus normal tissue. The increased expression of NUDT5 was also validated in the clinical specimens of gastric carcinoma by immunoblotting detection. Moreover, high NUDT5 levels predicted a poorer overall survival in gastric carcinoma patients. A series of cellular functional assays demonstrated that gastric carcinoma cells with silenced NUDT5 exhibited decreased proliferative and invasive ability, increased cell cycle arrest at the G0/G1 phase, and enhanced chemosensitivity. In-depth research showed that the silencing of NUDT5 led to a reduction in the activation of AKT and β-catenin. The reactivation of AKT blocked the repressive effect of NUDT5 silencing on β-catenin activation. The forced expression of β-catenin also reversed NUDT5-silencing-mediated anticancer effects. A Xenograft tumor assay confirmed the anticancer role of NUDT5 in gastric carcinoma in vivo. In short, these findings reveal elevated NUDT5 levels in gastric carcinoma and demonstrate that the inhibition of NUDT5 displays promising anticancer effects by affecting the AKT/β-catenin pathway. Thus, our work unveils a vital role of NUDT5 in gastric carcinoma and indicates it as a viable candidate target for anticancer drug discovery.

Slug, CD44 and Her-2/neu Immunohistochemical Expression in Gastric Carcinoma

Slug, CD44 and Her-2/neu Immunohistochemical Expression in Gastric Carcinoma

Expression of tight junction transmembrane protein Claudin-1 in gastric carcinoma and effects on tumor cell proliferation, invasion and migration

Abstract Background: Claudin-1 is involved in various cancers, but its expression and role in gastric carcinoma remain unclear. Materials and Methods: Gastric carcinoma and adjacent normal tissues were harvested from 60 patients. Claudin-1 expression was detected by RT-qPCR. The expressions in human gastric carcinoma MKN45, SGC7901 and MKN28 cells and immortalized human gastric epithelium GES-1 cells were determined by RT-qPCR and Western blotting. Claudin-1 was overexpressed in SGC7901 cells by lentiviral transfection, and they were divided into Control (untransfected), normal control (NC) (transfected with lentiviral vector) and Claudin-1 (transfected with Claudin-1 overexpression lentivirus) groups. The proliferation, invasion and migration of gastric carcinoma cells were detected through cell counting kit-8, Transwell and wound healing assays, respectively. The effects of Claudin-1 on the expressions of epithelial-mesenchymal transition (EMT) marker proteins E-cadherin and N-cadherin were detected by Western blotting. Ten 4-week-old male BALB/c nude mice were subcutaneously injected with lentivirus-treated SGC7901 cells to establish the transplanted tumor model, and the effect of overexpression of Claudin-1 was explored. Results: The expression of Claudin-1 in gastric carcinoma tissues was significantly lower than that in adjacent tissues (P&lt;0.05). Overexpression of Claudin-1 significantly inhibited the proliferation, invasion and migration of SGC7901 cells, increased the expression of E-cadherin, and decreased that of N-cadherin (P&lt;0.05). Overexpression of Claudin-1 in the mouse model significantly inhibited the growth of subcutaneous transplanted tumors (P&lt;0.05). Conclusion: Claudin-1 has low expression in gastric carcinoma tissues. Overexpression of Claudin-1 inhibits the proliferation, invasion, migration, and EMT of gastric carcinoma cells, and subcutaneous tumorigenesis in nude mice.

Immunohistochemical expression of FOXP3 in gastric carcinoma; its relation to Ki-67 proliferation marker, HER2/neu expression, and other clinicopathological parameters

ABSTRACT Gastric cancer is common cancer in the world. Contradictory results regarding FOXP3 expression in gastric carcinoma were detected and the role of Ki-67 in prognosis is not completely understood. Furthermore, due to increasing use of anti-HER2 drug trastuzumab for gastric cancer, assessment of HER2 expression becomes important. This study tried to assess the FOXP3 expression in gastric carcinoma and to study the relation between its expression and Ki-67 and HER2/neu expression and relation between their expression and other clinicopathological variables. This retrospective study was carried out on 60 gastric adenocarcinoma cases. Tissue microarrays and immunohistochemical staining for FOXP3, Ki-67 and HER2/neu were done and then assessed and scored. HER2/neu expression showed significant relation to Lauren histological type and lymph node status. High Ki-67 index was related significantly to patients’ age, lympho-vascular tumor emboli, peri-neural invasion, tumor grade, lymph node status, and cancer stage. There was significant relation between high FOXP3 expression and patients’ age, lympho-vascular tumor emboli, peri-neural invasion, tumor grade, lymph node status, and cancer stage. Direct positive significant relationships between HER2/neu, Ki-67, and FOXP3 expression were noticed. Finally, high FOXP3 expression, positive HER2/neu, and high Ki-67 nuclear proliferation index may be an indication of the aggressiveness of gastric carcinoma.

CD10 expression in gastric adenocarcinoma and its correlation with histopathological features and lymph node metastasis

Background: Gastric cancer is one of the most common cancers worldwide. Invasion and metastasis are known prognostic factors. Previous studies have suggested CD10 expression in the epithelium and stroma of various carcinomas is associated with more aggressive behavior of the tumor. Aims and Objective: To study the immunohistochemical expression of CD10 in stromal cells of gastric adenocarcinoma and to correlate the expression with various clinicopathological features and lymph node metastasis. Materials and Methods: A cross sectional study of CD10 expression in 40 cases of gastric carcinoma in gastrectomy specimens was done. CD10 expression was correlated with age, gender, tumor site, tumor grade, histologic sub type, depth of invasion and lymph node status. Results: Out of 40 cases, 72.5% were males and 27.5% were females. Majority of cases were seen in 6th and 7th decades. Antrum was the most common location (70%) and intestinal morphology was the commonest histologic subtype (47.5%). Tumor size ranged from 2.5 to 11cms. 40% tumors were well differentiated. Majority (62.5%) of the tumors were in T3 stage. 25 (62.5%) cases showed a positive CD10 expression in stromal cells. Stromal CD10 expression in gastric carcinoma did not correlate with the age and gender of the cases as well as the location and size of the tumor, histologic subtype and lymph node involvement but correlated with depth of invasion (T stage) (p &lt;0.05). Conclusion: CD10 expression in gastric adenocarcinoma shows a significant correlation with depth of invasion. CD10 may be used as an immunohistochemical surrogate of tumor behavior.

Diagnostic and prognostic value of MATN3 expression in gastric carcinoma: TCGA database mining.

Globally, the high morbidity and mortality of gastric carcinoma (GC) have been one of the great challenges facing humanity. However, the early diagnosis of GC is still unknown. Matrilin-3 (MATN3) is a member of the extracellular matrix (ECM) protein family. Previous studies have reported a correlation between the expression of MATN3 and bone disease. However, the role of MATN3 in GC has not been reported in depth, which can have a possible far-reaching implication for GC. We explored the diagnostic and prognostic value and pathway enrichment of MATN3 expression in GC. Limma package conducted by R was used to analysis the difference expression data of MATN3 from The Cancer Genome Atlas (TCGA). The receiver operating characteristic (ROC) curve analysis was used to estimate the diagnostic value of MATN3 expression. univariate and multivariate analysis were used to assess the prognostic value of MATN3, and gene set enrichment analysis (GSEA) to identify the enriched signaling pathways. MATN3 was found to be significantly higher in GC tissue samples. GC patients with high MATN3 expression had poor prognosis. Then, GSEA showed that the gene sets were correlated with signaling pathways including ECM receptor interaction, hypertrophic cardiomyopathy (HCM), and glycosaminoglycan biosynthesis chondroitin sulfate, among others. The study suggests that MATN3 can serve as a potential diagnostic and prognostic biomarker for GC.

The Analysis of Human Epidermal Growth Receptor-2 (HER-2) in Gastric Cancer in a Tertiary Hospital in Sub-Saharan Africa.

In Ghana, gastric cancer contributes significantly to cancer morbidity and mortality. However, the recent usage of HER-2 monoclonal antibody in combination with chemotherapy has greatly improved the overall survival of patients. This study, therefore, aims at evaluating the pattern of HER-2 over expression in gastric carcinomas in Kumasi, Ghana. Demographic data and histological diagnosis were retrieved from the surgical daybook of the Department of Pathology, Komfo Anokye Teaching Hospital, Kumasi. The slides were retrieved and reviewed to confirm the diagnosis, grading and classification of gastric cancer and immunohistochemistry was done with anti-HER-2 antibody to confirm HER-2 over-expression. Results: Of the 99 cases of gastric cancer seen over the 8 years, there were 57 males and 42 females. There were 91 adenocarcinomas, 5 GIST and 3 Non-Hodgkin Lymphoma. The age range of the study population was 8-90 years with a modal age group in the 6th decade. Of the adenocarcinomas, 45 were poorly differentiated, 38 moderately differentiated and 8 well differentiated. The diffuse type was most common with 47 cases followed by intestinal-type with 41cases and mixed type with 3 cases. Three of the 4 patients under the age of 30 years had lymphoma. HER-2 over expression was seen in 14 out of the 47 tested and all were intestinal type. HER -2 over-expression was seen in 30% of patients with gastric carcinoma especially those with intestinal-type.

Gastrik Karsinomlarda PD-L1 ve FOXP3 Ekspresyonlarının Klinikopatolojik Parametrelerle İlişkisinin Değerlendirilmesi

Objective: At the time of diagnosis, gastric cancers are generally at an advanced stage and the survival rates are very low. The aim of this study is to determine the prognostic values of PD-L1 expression in gastric carcinomas and to detect the presence of FOXP3- positive Treg cells in tumor microenviroment. Method: In this study, PD-L1 and FOXP3 expressions were evaluated in 125 patients with gastric carcinoma who had undergone gastrectomy between 2011, and 2015. Results: The mean age of the patients was 64.18±12.3 years and the patients were followed up for a mean period of 29.6±26.4 months. In only 2 (1.6%) cases there were weak membranous expressions of PD-L1 in tumor cells. PD-L1- positive inflammatory cells were also seen in tumors of 2 (1.6%) cases. There was no significant relationship between PD-L1 expression and survival times (p= 0.690). In 57(45.6%) cases, FOXP3- positive lymphocytes were detected. The number of FOXP3-positive cells ranged between 1 and 55/HPF. There was no statistically significant correlation between the survival times and presence of Tregs (p=0.793). Twenty-two cases (17.6%) were evaluated as HER2-positive. There was a statistical relationship between HER2-positivity and perineural invasion (p=0.006). Statistical significance between survival and some prognostic factors such as nodal metastasis (p=0.004), pT stage (p&lt;0.01) and presence of perineural invasion (p=0.010) was determined. Conclusion: This study has demonstrated that the PD-L1 positivity was not effective on gastric tumorigenesis. We have found a positive correlation between the presence of Treg inflammatory cells and PD-L1 expression. But this relationship could not be proved by statistical analyses. However since PD-L1 expression was detected in only 4 cases, these findings should be confirmed in larger series.

Association of MALAT1 expression in gastric carcinoma and the significance of its clinicopathologic features in an Iranian patient.

The aim of this study was to evaluate the expression of MALAT1 and the relationship between its expression with clinical characteristics in an Iranian gastric cancer patient. Long non-coding RNAs (LncRNAs) play critical roles in the initiation and development of gastric cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly conserved lncRNA and plays key roles in various types of human cancer. However, our understanding of the role of lncRNAs in the occurrence and development of gastric cancer is not fully clear. This cross-sectional study was performed on 41 gastric tumor tissue samples with matched normal adjacent tumor tissues. The RNA level of lncRNA MALAT1 gene was assessed using quantitative Real-time polymerase chain reaction. B2M was used as an internal control. The 2 -ΔΔCq method was adopted to determine expression fold changes. A significant association was observed between the levels of MALAT1 in gastric tumor tissues compared with normal adjacent tissues (mean= 1.558, p= 0.014). In addition, clinicopathologic data on MALAT1 RNA expression levels in gastric cancer tissues was evaluated. No significant association was observed between the relative expression of MALAT1 and the stage, grade, H. pylori infection, and tumor size groups among gastric cancer patients (p= 0.82, p= 0.904, p= 0.407, and p= 0.701, respectively). The current results showed that MALAT1 has a significant association in gastric cancer. The expression of MALAT1 may be used as a diagnostic biomarker for monitoring gastric cancer patients.