Types Of Gastric Tumors Research Articles

Gastric Perineurioma: A Rare Entity with Molecular Analysis and Literature Review.

Perineuriomas of the gastrointestinal tract are benign neoplasms that commonly develop in the distal colon and are identified during screening colonoscopy; however, perineuriomas of the stomach are exceedingly rare and less frequently identified. Differentiating gastric perineuriomas from other more serious gastric neoplasms is critical to avoid unnecessarily aggressive treatments. Thus far, only six patients with gastric perineurioma have been described, and the molecular characterization of this entity is still lacking. We report a 52-year-old woman who presented with abdominal pain and gastric acid reflux and was found to have a 1.5 cm subepithelial gastric neoplasm composed of bland spindle cells displacing the gastric glands with no cytologic atypia or mitotic activity, suggesting a benign spindle cell neoplasm. Immunohistochemical analysis showed reactivity for perineurial markers glucose transporter-1 and epithelial membrane antigen, consistent with benign gastric perineurioma. DNA extracted from the tissue was used for a capture-based target sequence enrichment panel followed by Illumina next-generation sequencing and targeted bioinformatic analysis for oncogenic alterations within defined disease-associated target regions. No sequence variants in the BRAF gene were identified. This rare case of gastric perineurioma helps solidify our understanding of how to discern various types of gastric neoplasms through traditional laboratory analysis alongside genetic sequencing approaches. Although extremely rare, gastric perineurioma should be kept in the differential diagnosis when assessing spindle cell gastric tumors to avoid unnecessary therapies, and physicians should understand the molecular characteristics of benign versus malignant tumors.

A nomogram for predicting lymph node metastasis in early gastric cancer

Objective: To explore the independent risk factors of lymph node metastasis (LNM) in early gastric cancer, and to use nomogram to construct a prediction model for above LNM. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) primary early gastric cancer as stage pT1 confirmed by postoperative pathology; (2) complete clinicopathological data. Exclusion criteria: (1) patients with advanced gastric cancer, stump gastric cancer or history of gastrectomy; (2) early gastric cancer patients confirmed by pathology after neoadjuvant chemotherapy; (3) other types of gastric tumors, such as lymphoma, neuroendocrine tumor, stromal tumor, etc.; (4) primary tumors of other organs with gastric metastasis. According to the above criteria, 1633 patients with early gastric cancer who underwent radical gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital First Medical Center from December 2005 to December 2020 were enrolled as training set, meanwhile 239 patients with early gastric cancer who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital Fourth Medical Center from December 2015 to December 2020 were enrolled as external validation set. Risk factors of LNM in early gastric cancer were identified by using univariate and multivariate logistic regression analyses. A nomogram prediction model was established with significant factors screened by multivariate analysis. Area under the receiver operating characteristic curve (AUC) was used for assessing the predictive value of the model. Calibration curve was drawn for external validation. Results: Among 1633 patients in training set, the mean number of retrieved lymph nodes was 20 (13-28), and 209 patients (12.8%) had lymph node metastasis. Univariate analysis showed that gender, resection range, tumor location, tumor morphology, lymph node clearance, vascular invasion, lymphatic cancer thrombus, tumor length, tumor differentiation, microscopic presence of signet ring cells and depth of tumor invasion were associated with LNM (all P<0.05). Multivariate analysis revealed that females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa, and poor differentiation were independent risk factors for LNM in early gastric cancers (all P<0.05). Receiver operating characteristic curve indicated that AUC of training set was 0.818 (95%CI: 0.790-0.847) and AUC of external validation set was 0.765 (95%CI: 0.688-0.843). The calibration curve showed that the LNM probability predicted by nomogram was consistent with the actual situation (C-index: 0.818 in training set and 0.765 in external validation set). Conclusions: Females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa and poor differentiation are independent risk factors for LNM of early gastric cancer. The establishment of a nomogram prediction model for LNM in early gastric cancer has great diagnostic value and can provide reference for treatment selection.

Endoscopic Findings and Treatment of Gastric Neoplasms in Familial Adenomatous Polyposis.

Gastric neoplasia is a common manifestation of familial adenomatous polyposis (FAP). This study aimed to elucidate the clinical characteristics, endoscopic features including fundic gland polyposis (FGPsis), and treatment outcomes of gastric neoplasms (GNs) in patients with FAP. A total of 35 patients diagnosed with FAP, including nine patients from four pedigrees who underwent esophagogastroduodenoscopy (EGD), were investigated regarding patient characteristics, GN morphology, and treatment outcomes. Twenty-one patients (60.0%) had 38 GNs; 33 (86.8%) and 5 (13.2%) were histologically diagnosed with adenocarcinoma and adenoma, respectively. There were no specific patient characteristics related to GNs. Nodule-type GNs were more prevalent in patients with FGP than without (52.2% vs. 0.0%, P=0.002) in the upper body of the stomach. Conversely, depressed-type GNs were fewer in patients with FGPsis than in those without (13.0% vs. 73.3%, P<0.001). Slightly elevated-type GNs were observed in both groups (34.8% vs. 20.0%, P=0.538). Even within pedigrees, the background gastric mucosa and types of GNs varied. In total, 24 GNs were treated with endoscopic submucosal dissection (ESD) and eight with endoscopic mucosal resection (EMR). EMR was selected for GNs with FGPsis because of the technical difficulty of ESD, resulting in a lower en bloc resection rate (62.5% vs. 100%, P=0.014). Our study indicates the necessity of routine EGD surveillance in patients diagnosed with FAP. Notably, the morphology and location of GNs differed between patients with and without FGPsis. Endoscopic treatment and outcomes require more attention in cases of FGPsis.

Identification of kinases and kinase inhibitors for the differential targeting of Wnt/β-catenin signaling in gastric cancer subtypes.

The oncogenic signaling pathway Wnt is often activated in many cancers including gastric cancer. Wnt signaling pathway is considered as a potential target for developing new targeted therapeutics. Kinase inhibitors are the promising class of drugs for many diseases including cancers. Toward identifying the potent inhibitors targeting Wnt signaling pathway, a kinase inhibitor library with 82 inhibitors were screened using Wnt pathway reporter assay in gastric cancer cells. Notably, 34 kinase inhibitors were identified to inhibit Wnt mediated reporter activity to the extent of more than 50%. The corresponding kinase genes, which are known targets of these kinase inhibitors, were investigated for their expression in the available mRNA profiles of gastric tumors. A major group of the kinase genes showed higher expression in intestinal subtype gastric tumors. Another group of kinase genes were found expressed in diffuse type gastric tumors. The kinase genes expressed in intestinal type gastric tumors were found associated with varying survival of gastric cancer patients whereas those expressed in diffuse type tumors were found associated with the poor survival. Thus, the kinase genes specifically expressed in intestinal and diffuse type gastric tumors and the kinase inhibitors to target Wnt signaling pathway in gastric cancer subtypes have been identified.

Gut microbiota of patients with different subtypes of gastric cancer and gastrointestinal stromal tumors

BackgroundGastric adenocarcinoma is associated with H. pylori infection and inflammation that can result in the dysbiosis of gastric microbiota. The association of intestinal microbiota with gastric adenocarcinoma subtypes or with gastric gastrointestinal stromal tumors (GIST) is however not well known. Therefore, we performed 16S rRNA gene sequencing on DNA isolated from stool samples of Finnish patients and controls to study differences in microbiota among different histological subtypes of gastric adenocarcinoma, gastric GIST and healthy controls.ResultsWe found that gut microbiota alpha diversity was lowest in diffuse adenocarcinoma patients, followed by intestinal type and GIST patients, although the differences were not significant compared to controls. Beta-diversity analysis however showed significant differences in microbiota composition for all subtypes compared to controls. Significantly higher abundance of Enterobacteriaceae was observed in both adenocarcinoma subtypes, whereas lower abundance of Bifidobacteriaceae was seen only in diffuse adenocarcinoma and of Oscillibacter in intestinal adenocarcinoma. Both GIST and adenocarcinoma patients had higher abundance of Enterobacteriaceae and lower abundance of Lactobacillaceae and Oscillibacter while lower abundance of Lachnoclostridium, Bifidobacterium, Parabacteroides and Barnesiella was seen only in the adenocarcinoma patients.ConclusionsOur analysis shows association of higher Enterobacteriaceae abundance with all types of gastric tumors. Therefore it could be potentially useful as a marker of gastric malignancies. Lower gut microbiota diversity might be indicative of poorly differentiated, invasive, advanced or aggressive tumors and could possibly be a prognostic marker for gastric tumors.

Proton pump inhibitors and stomach neoplasm

Abstract This study aimed to explore the relationship between proton pump inhibitors (PPIs) and gastric tumors and determine the reasons behind these connections. We reviewed studies on PPIs and stomach tumors. We explored the relationship between PPIs and different types of gastric neoplasms according to the classification of gastric neoplasms. Long-term use of PPIs is associated with stomach infection, high gastrin levels, and rebound acid hypersecretion, which are directly or indirectly related to the development of gastric neoplasms. PPIs can increase the risk of gastric fundal polyps. Further evidence is needed to prove that it can increase the risk of gastric cancer.

Contrast-enhanced computed tomography may be helpful for characterizing and staging canine gastric tumors.

In humans, computed tomography (CT) is a widely performed technique for the diagnosis and staging of gastric tumors. The purpose of this retrospective case series study was to describe CT findings in a group of dogs with confirmed gastric tumors. For each included dog, the following CT parameters were recorded: gastric tumor location, tumor shape, gastric involvement pattern, tumor enhancement pattern in early and late phases, presence and location of lymphadenopathy, gastric tumor attenuation values, attenuation values of enlarged lymph nodes, maximum short-axis diameter (mm) of enlarged lymph node, maximum long-axis diameter (mm) of enlarged lymph node, and short-axis diameter to long-axis diameter ratio (short axis/long axis). A total of 16 dogs met inclusion criteria and had the following final diagnoses: five lymphoma, six adenocarcinoma, three inflammatory polyps, and two leiomyoma. In the early- and delayed-phase postcontrast images, the mean CT attenuation value for lymphoma was lower than that of other gastric tumors. Lymphadenopathy was widespread in lymphomas and regional in adenocarcinomas. Lymphadenopathy was not detected in leiomyomas. Lymph node measurements in lymphoma were larger than lymph node measurements in adenocarcinoma. Although there were overlapping findings for the different types of gastric tumors, contrast-enhanced CT provided helpful information for characterizing gastric tumors based on the following criteria: early and late enhancement patterns, the site of origin of the mass lesion, and extent of local invasion and distant metastases. Lymphoma should be considered for canine gastric tumors with low mean attenuation values during early- and delayed-phase postcontrast images, and widespread, bulky, and rounded lymphadenopathy.

Autoimmunity and Gastric Cancer.

Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms.

Comparing intestinal versus diffuse gastric cancer using a PEFF-oriented proteomic pipeline

Gastric cancer is the fifth most common malignant neoplasia and the third leading cause of cancer death worldwide. Mac-Cormick et al. recently showed the importance of considering the anatomical region of the tumor in proteomic gastric cancer studies; more differences were found between distinct anatomical regions than when comparing healthy versus diseased tissue. Thus, failing to consider the anatomical region could lead to differential proteins that are not disease specific. With this as motivation, we compared the proteomic profiles of intestinal and diffuse adenocarcinoma from the same anatomical region, the corpus. To achieve this, we used isobaric labeling (iTRAQ) of peptides, a 10-step HILIC fractionation, and reversed-phase nano-chromatography coupled online with a Q-Exactive Plus mass spectrometer. We updated PatternLab to take advantage of the new Comet-PEFF search engine that enables identifying post-translational modifications and mutations included in neXtProt's PSI Extended FASTA Format (PEFF) metadata. Our pipeline then uses a text-mining tool that automatically extracts PubMed IDs from the proteomic result metadata and drills down keywords from manuscripts related with the biological processes at hand. Our results disclose important proteins such as apolipoprotein B-100, S100 and 14-3-3 proteins, among many others, highlighting the different pathways enriched by each cancer type. SignificanceGastric cancer is a heterogeneous and multifactorial disease responsible for a significant number of deaths every year. Despite the constant improvement of surgical techniques and multimodal treatments, survival rates are low, mostly due to limited diagnostic techniques and late symptoms. Intestinal and diffuse types of gastric cancer have distinct clinical and pathological characteristics; yet little is known about the molecular mechanisms regulating these two types of gastric tumors. Here we compared the proteomic profile of diffuse and intestinal types of gastric cancer from the same anatomical location, the corpus, from four male patients. This methodological design aimed to eliminate proteomic variations resulting from comparison of tumors from distinct anatomical regions. Our PEFF-tailored proteomic pipeline significantly increased the identifications as when compared to previous versions of PatternLab.

Glutathione system to characterize the biological aggressiveness of the gastric cancer.

e15512 Background: The aim was a comparative study of glutathione system of tumor and its peritumoral tissues at gastric signet ring cell carcinoma (SRCC) and gastric adenocarcinoma (AC) to identify pathogenetic features of malignancy. Methods: Content of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST) were determined in the samples of tumor and peritumoral tissues, obtained during the surgery in 21 primary patients: 13 patients with SRCC, 8 patients with AC (G2-G3) without preoperative therapy. Tissue of intact stomach was studied in 12 randomly bereaved. Results: In the AC tumor tissue the GSH level was decreased by 43% and the activity of GPx and the GST was increased by 121.7% and 44.3% (p &lt; 0.05–p &lt; 0.001) compared with intact stomach. In peritumoral tissue both the level of GSH and GPX activity were less than in the tumor tissue at 40-45% (p &lt; 0.05–p &lt; 0.01). In SRCC both the GSH level and the activity of GPx and GST were increased in tumor tissue by 78%, 93.6% and 49.5% (p &lt; 0.05–p &lt; 0.001) compared with the intact stomach. In peritumoral tissue the GSH level was lower than in the tumor tissue by 60.2% (p &lt; 0.01), the enzymes activity was unchanged remaining higher than in the intact stomach. The GSH level both in tumor and in peritumoral tissues was 2-3 folds higher in gastric SRCC than in AC. No significant differences in the activity of glutathione-dependent enzymes in tumors of different histotype were revealed. Conclusions: The results show the differences in the functioning of the glutathione system, depending on the histological type of gastric tumors. It is possible that greater activity of glutathione-dependent system in tissue of SRCC is needed to maintain its increased proliferative activity and determines the features of the biological behavior of this tumor histotype.

Amplified 7q21-22 gene MCM7 and its intronic miR-25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features.

Frequent amplification of 7q21-22 genomic region is known in gastric cancer. Multiple genes including SHFM1, MCM7, and COL1A2 were reported to be the potential cancer candidate genes of this 20 Mb amplicon. This amplicon has two polycistrionic miRNA clusters and in the present study, miR-106b-25 cluster located in intron-13 of MCM7 was identified to express in gastric tumors. Among the 7q21-22 candidate genes, SHFM1 and MCM7 are expressed in intestinal type gastric tumors, whereas COL1A2 is expressed in diffuse type gastric tumors. Across gastric tumors, miR-25 was identified to co-express with MCM7 and SHFM1. On the other hand, negative correlation was observed between miR-25 and COL1A2 expression. miR-25 originating from MCM7 was found capable of selectively targeting the adjacent gene COL1A2. Silencing of miR-25 was found capable of elevating the expression of COL1A2 and inhibiting E-cadherin expression, revealing the diffuse type gastric cancer suppressive role conferred by miR-25. miR-25 was also found to suppress p53, and activate c-Src revealing its intestinal type gastric cancer associated oncogenic functions. Genome-wide expression profiling upon miR-25 silencing reveals that miR-25 is capable of suppressing 40 genes which are co-expressed with COL1A2, involved in epithelial to mesenchymal transition and angiogenesis which are the typical diffuse type gastric cancer features. The results clearly demonstrate 7q21-22 amplification, MCM7, and its intronic miR-25 are the major molecular switches involved in the complex oncogenic circuits of gastric cancer.

Interleukins 17 and 23 in patients with gastric neoplasms.

Recently there has been heightened interest in the potential significance of interleukin (IL)-17 and IL-23 in the development/progression of human malignancies. Here, we analyzed the systemic levels of these cytokines in 75 patients with different types of gastric neoplasms (carcinoma, gastrointestinal stromal tumors, neuroendocrine neoplasms, and lymphomas) and 42 healthy volunteers. We found that patients with all types of gastric neoplasms have significantly lower IL-23 levels. However, in comparison to the levels in healthy individuals, IL-17 concentrations were lower only in patients with types of gastric neoplasms other than carcinoma. Interestingly, IL-17 levels significantly differed between patients with early and advanced gastric carcinoma. No significant associations were detected between the systemic levels of examined interleukins and TNM staging. However, peripheral levels of IL-23 were correlated with the absolute numbers of circulating populations of bone marrow-derived mesenchymal and very small embryonic/epiblast-like stem cells in patients with gastric carcinoma. ROC curve analyses demonstrated that systemic levels of IL-17 seem to meet basic criteria for consideration as a helpful diagnostic marker in the detection of gastric carcinoma. In conclusion, our study provides translational evidence confirming the clinical significance of IL-17 and IL-23 in the pathogenesis of different types of gastric neoplasms in humans.

Juxtaposed genes in 7q21-22 amplicon contribute for two major gastric cancer sub-Types by mutual exclusive expression.

Genomic Copy Number Variations (CNV) and the associated gene signatures are useful for cancer prognosis, diagnosis, and targeted therapeutics. Earlier, 7q21-22 region was reported for frequent amplification in gastric cancer and potential candidate genes were identified. An analysis of the expression pattern of the 159 genes located in this amplicon revealed the consistent elevated expression of 21 genes in gastric tumors. These genes are closely arranged within the 20 Mb region, and they showed a bimodal expression pattern. SHFM1 and 14 other genes are expressed in intestinal type gastric tumors. COL1A2 and PCOLCE genes of this region are expressed in diffuse type gastric tumors. Similarly, genome-wide expression neighbors of SHFM1 and COL1A2 also showed mutually exclusive expression pattern, and stratify intestinal and diffuse type gastric tumors. The expression of COL1A2 gene-set is associated with poor prognosis, whereas the SHFM1 gene-set is associated with better prognosis among the gastric cancer patients. Despite being physical neighbors, the SHFM1 and COL1A2 genes express differentially in the two major clinical sub-types of gastric cancer in a mutually exclusive manner. The tight gene regulations operating between these juxtaposed genes deserve investigation to understand the molecular regulatory switch defining the determinants of the gastric cancer sub-types. © 2016 Wiley Periodicals, Inc.

Peripheral trafficking of bone marrow-derived stem cells in patients with different types of gastric neoplasms: Significance of complement and interleukins.

49 Background: Increasing evidence suggests that gastric malignancy may be a stem cell disorder. Methods: Using FACS analysis supported by ImageStream technique verification, various populations of bone marrow-derived stem cells (BMSCs), such as Lin-CD45-CD133+CXCR4+ very small embryonic/epiblast-like stem cells (VSELs), CD45-STRO-1+CD105+ mesenchymal stem cells (MSCs), Lin-CD45+CD133+ hematopoietic stem/progenitor cells (HSPCs), and CD34 +/ KDR +/ CD31 +/ CD45- endothelial progenitor cells (EPCs) were enumerated and sorted from peripheral blood samples of patients with gastric cancer (n = 23) and other gastric tumors (GISTs, NENs, lymphomas; n = 15) and control patients (n = 15). RT-qPCR analysis for the expression of cancerous, embryonic, and tissue trans-differentiation markers (Oct-4, Nanog, TFF-1, TFF-2, Lgr-5, BMI-1) in circulating VSELs was employed. The plasma levels of stromal-derived factor-1 (SDF-1), complement-derived anaphylatoxins/molecules (C3a, C5a, C5b-9/MAC), and interleukins (IL-6, IL-8, IL-17 and IL-23) were measured. Results: Significantly lower numbers of circulating HSPCs, and intensified peripheral trafficking of both VSELs and MSCs was observed in patients with gastric cancer, but not in those with other types of gastric tumors. In gastric cancer patients, the circulating VSELs presented higher gene expression of Oct-4, Nanog, Lgr-5, BMI-1, and TFF-1/2. The abnormal balance in the peripheral trafficking of BMSCs in patients with gastric cancer was not associated with the clinical stage of the disease or with the systemic levels of stromal-derived factor-1 (SDF-1), but correlated with the levels of C5b-9/MAC, IL-6, IL-8 and IL-23. Conclusions: Abnormal peripheral trafficking of BMSCs occurs in patients with gastric cancer, but not in those with other types of gastric neoplasms. Selected interleukins and complement cascade-derived molecules, but not SDF-1, seem to be significant players associated with this phenomenon (POIG.01.01.02-00-109/09 and IP2014003273).

Clinicopathological Characteristics, Treatment, and Prognosis of 21 Patients with Primary Gastric Squamous Cell Carcinoma.

We performed a retrospective analysis of 21 patients with primary gastric squamous cell carcinoma (PGSCC) who were admitted to our hospital from October 2008 to October 2014. The median age was 67 years and male predominance was observed, the most common tumor locations were the upper third of the stomach, most of the clinical manifestations were identical to those of other types of gastric tumors, and the tumor cells had positive immunoreactivity for p63 and CK5/6. In terms of treatments, surgery (R0 resection) is the main treatment; the effect of other treatments is unclear. The median survival time for the surgery group and nonsurgery group was 46 and 4.5 months, respectively. Probably due to limited number of cases, no significant difference in median survival time was observed between the surgery alone group and the surgery plus adjuvant therapy group (46 versus 51 months, P = 0.310). A standard chemotherapy regimen for this disease has not yet been established; the choice of its chemotherapy regimens tends to follow the principle of the treatment of gastric adenocarcinoma or esophageal cancer. PGSCC generally had a poor prognosis, and early detection, early diagnosis, and early surgical treatment are beneficial to patients.

Peripheral trafficking of bone-marrow-derived stem cells in patients with different types of gastric neoplasms

ABSTRACTRecently, there has been a growing interest in the importance of stem cells (SCs) in the development/progression of gastric neoplasms. In this study, we performed a comprehensive analysis of different populations of bone-marrow-derived stem cells (BMSCs) in patients with various types of gastric malignancies, including gastric cancer, gastrointestinal stromal tumors (GISTs), neuroendocrine neoplasms (NENs), and lymphomas. We found significantly lower numbers of circulating Lin-/CD45 +/ CD133 + hematopoietic stem/progenitor cells (HSPCs), and intensified peripheral trafficking of both Lin−/CD45−/CXCR4+/CD34+/CD133+ very small embryonic/epiblast-like stem cells (VSELs) and CD105 + /STRO-1 +/ CD45- mesenchymal SCs (MSCs) in patients with gastric cancer, but not in those with other types of gastric neoplasms. No significant differences in the absolute numbers of circulating CD34 +/ KDR +/ CD31 +/ CD45- endothelial progenitor cells (EPCs) were observed between the groups. This abnormal balance in the peripheral trafficking of BMSCs in patients with gastric cancer was neither associated with clinical stage of the disease nor with systemic levels of stromal-derived factor-1 (SDF-1), as these were comparable to the values observed in control individuals. Interestingly, the absolute numbers of circulating BMSCs correlated with the concentrations of complement cascade-derived anaphylatoxins/molecules (mainly C5b-9/membrane attack complex-MAC) and sphingosine-1-phosphate (S1P). In summary, our translational study revealed that abnormal peripheral trafficking of BMSCs occurs in patients with gastric cancer, but not in those with other types of gastric neoplasms. Further, our findings indicate that highlighted complement cascade-derived molecules and S1P, but not SDF-1, are significant players associated with this phenomenon.

Evaluation of selected interleukins in patients with different gastric neoplasms: a preliminary report.

Abnormal interactions between cytokines may be an overlooked mechanism linking the development of different types of gastric neoplasms. In this study a comprehensive analysis of the systemic levels of interleukins (IL-1,IL-6, IL-8,IL-10 and IL-12) was performed in 75 patients with different gastric neoplasms (cancer, gastrointestinal stromal tumors, neuroendocrine neoplasms, lymphomas) and 40 healthy volunteers. Patients with gastric cancer (GC) have significantly higher IL-6 levels, and lower IL-8 and IL-10 concentrations, in comparison to controls and patients with other gastric neoplasms. Analogous results were observed in terms of IL-6/IL-8 and IL-6/IL-10 ratios, whose values were also higher in GC patients. In GC patients no associations were detected between the systemic levels/values of interleukins (ratios) and TNM staging. IL-6, IL-10, IL-6/IL-8 and IL-6/IL-10 ratios appeared to hold diagnostic potential in confirming/excluding the presence of GC. Their sensitivity/specificity in GC detection/exclusion was approximately 54–72%. In conclusion, disturbed systemic biochemical balance in multiple interleukins exists at the earliest stages of and appears to be specific to GC. The interleukin ratios proposed here seem to be more promising indicators of GC in humans than direct systemic levels of interleukins, and probably possess the potential to be applied as a supporting factor for techniques routinely used.

Transcriptional coexpression network reveals the involvement of varying stem cell features with different dysregulations in different gastric cancer subtypes

Despite the advancements in the cancer therapeutics, gastric cancer ranks as the second most common cancers with high global mortality rate. Integrative functional genomic investigation is a powerful approach to understand the major dysregulations and to identify the potential targets toward the development of targeted therapeutics for various cancers. Intestinal and diffuse type gastric tumors remain the major subtypes and the molecular determinants and drivers of these distinct subtypes remain unidentified. In this investigation, by exploring the network of gene coexpression association in gastric tumors, mRNA expressions of 20,318 genes across 200 gastric tumors were categorized into 21 modules. The genes and the hub genes of the modules show gastric cancer subtype specific expression. The expression patterns of the modules were correlated with intestinal and diffuse subtypes as well as with the differentiation status of gastric tumors. Among these, G1 module has been identified as a major driving force of diffuse type gastric tumors with the features of (i) enriched mesenchymal, mesenchymal stem cell like, and mesenchymal derived multiple lineages, (ii) elevated OCT1 mediated transcription, (iii) involvement of Notch activation, and (iv) reduced polycomb mediated epigenetic repression. G13 module has been identified as key factor in intestinal type gastric tumors and found to have the characteristic features of (i) involvement of embryonic stem cell like properties, (ii) Wnt, MYC and E2F mediated transcription programs, and (iii) involvement of polycomb mediated repression. Thus the differential transcription programs, differential epigenetic regulation and varying stem cell features involved in two major subtypes of gastric cancer were delineated by exploring the gene coexpression network. The identified subtype specific dysregulations could be optimally employed in developing subtype specific therapeutic targeting strategies for gastric cancer.

In silico analysis of expression pattern of a Wnt/β-catenin responsive gene ANLN in gastric cancer.

Actin-binding protein anillin (ANLN) is primarily involved in the cytokinesis and known to be dysregulated in many cancers including gastric cancer (GC). However, the regulation and clinical significance of ANLN in GC are far less clear. In the present study, we aimed to investigate the clinical significance and possible regulators of ANLN in GC. We have identified the Wnt/β-catenin associated regulation of ANLN by analyzing the in vitro perturbed β-catenin mRNA expression profiles. Investigating the gastric tumors from publicly available genome-wide mRNA expression profiles, we have identified the over expression of ANLN in gastric tumors. Association between ANLN expression and clinical characteristics of GC showed elevated expression in intestinal type GC. Performing a single sample prediction method across GC mRNA expression profiles, we have identified the over expression of ANLN in proliferative type gastric tumors compared to the invasive and metabolic type gastric tumors. In silico pathway prediction analysis revealed the association between Wnt/β-catenin signaling and ANLN expression in gastric tumors. Our results highlight that expression of a Wnt/β-catenin responsive gene ANLN in GC is a molecular predictor of intestinal and proliferative type gastric tumors.

Upper GI Tract Lesions in Familial Adenomatous Polyposis (FAP)

Patients with familial adenomatous polyposis (FAP), an autosomal dominant cancer predisposition syndrome caused by mutations in the APC gene, develop neoplasms in both the upper and lower gastrointestinal (GI) tract. To clarify the upper GI tract lesions in FAP patients in a tertiary care setting, we reviewed specimens from 321 endoscopies in 66 patients with FAP. Tubular adenomas in the small bowel were the most common neoplasms (present in 89% of patients), although only 1 patient developed invasive carcinoma of the small bowel. Several types of gastric neoplasms were identified--65% of patients had at least 1 fundic gland polyp, and 23% of patients had at least 1 gastric foveolar-type gastric adenoma. Pyloric gland adenomas were also enriched, occurring in 6% of patients--this is a novel finding in FAP patients. Despite the high frequency of gastric neoplasms, only 1 patient developed carcinoma in the stomach. The very low frequency of carcinoma in these patients suggests that current screening procedures prevent the vast majority of upper GI tract carcinomas in patients with FAP, at least in the tertiary care setting.