Gastric Adenocarcinoma Patients Research Articles

GINS Complex Subunit 2 Facilitates Gastric Adenocarcinoma Proliferation and Indicates Poor Prognosis.

Gastric cancer is the one of the most lethal malignancies of digestive system. Identifying molecular biomarkers is invaluable in help predicting clinical outcomes and developing targeted chemotherapies. GINS complex subunit 2 (GINS2) plays an essential role in the initiation and elongation of DNA replication. Although there have been studies revealing the prognostic significance of GINS2 in breast cancer and lung cancer, its involvement and function in gastric cancer need to be elucidated. We retrospectively enrolled a cohort of gastric adenocarcinoma patients after surgical resection (n = 123). By analyzing the mRNA and protein levels of GINS2 in tissue samples, we found that GINS2 presented a higher expression in tumor tissues than in adjacent normal stomach tissues. Besides, GINS2 level was positively correlated with tumor size and gastric adenocarcinoma tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower GINS2 showed a better overall survival compared to those with higher GINS2 expression. In addition, cellular and xenograft experiments confirmed the role of GINS2 in facilitating tumor proliferation both in vitro and in vivo. To our knowledge, this is the initial finding on GINS2 in promoting gastric adenocarcinoma progression. In conclusion, our study revealed a pro-oncogenic role of GINS2 in gastric cancer.

Gastric Cancer Treatments and Survival Trends in the United States.

Gastric cancer is the third most common cause of cancer deaths worldwide. Despite evidence-based recommendation for treatment, the current treatment patterns for all stages of gastric cancer remain largely unexplored. This study investigates trends in the treatments and survival of gastric cancer. The National Cancer Database was used to identify gastric adenocarcinoma patients from 2004–2016. Chi-square tests were used to examine subgroup differences between disease stages: Stage I, II/III and IV. Multivariate analyses identified factors associated with the receipt of guideline concordant care. The Kaplan–Meier method was used to assess three-year overall survival. The final cohort included 108,150 patients: 23,584 Stage I, 40,216 Stage II/III, and 44,350 Stage IV. Stage specific guideline concordant care was received in only 73% of patients with Stage I disease and 51% of patients with Stage II/III disease. Patients who received guideline consistent care had significantly improved survival compared to those who did not. Overall, we found only moderate improvement in guideline adherence and three-year overall survival during the 13-year study time period. This study showed underutilization of stage specific guideline concordant care for stage I and II/III disease.

TGFB1 polymorphisms and TGF‐β1 plasma levels identify gastric adenocarcinoma patients with lower survival rate and disseminated disease

TGF‐β1 is involved in tumour growth. Four TGFB1 SNPs and TGF‐β1 production by stimulated PBMC were determined in seventy‐eight gastric adenocarcinoma patients. In addition, TGF‐β1 levels were measured in the plasma of further thirty patients. rs1800471‐G/C genotype was prevalent in patients (20.7%) compared to controls (8.4%), as it also was the rs1800468 SNP‐G/A genotype in stage IV patients (20.7%) compared to stage I, II and III patients, combined (10.3%). Conversely, the T/T rs1800469 SNP‐T/T genotype was absent in the former group and present in 19.0% in the latter. Furthermore, the rs1800469‐C/rs1800470‐T (CT) haplotype was found in 15.0% of stage IV patients as compared to 3.0% of the remaining patients (3.0%) and also identifies patients with worse five‐year life expectancy (P = .03). TGF‐β1 synthesis by stimulated PBMCs was significantly lower in patients with the risk SNPs or haplotype, compared to the alternative genotype. Finally, TGF‐β1 plasma levels were lower in patients with worse life expectancy. Analysis of TGFB1 SNPs and measurement of plasma TGF‐β1 levels serves to identify patients at risk of developing a more aggressive disease.

Gastrointestinal adenocarcinoma analysis identifies promoter methylation-based cancer subtypes and signatures

Gastric adenocarcinoma (GAC) and colon adenocarcinoma (CAC) are the most common gastrointestinal cancer subtypes, with a high incidence and mortality. Numerous studies have shown that its occurrence and progression are significantly related to abnormal DNA methylation, especially CpG island methylation. However, little is known about the application of DNA methylation in GAC and CAC. The methylation profiles were accessed from the Cancer Genome Atlas database to identify promoter methylation-based cancer subtypes and signatures for GAC and CAC. Six hypo-methylated clusters for GAC and six hyper-methylated clusters for CAC were separately generated with different OS profiles, tumor progression became worse as the methylation level decreased in GAC or increased in CAC, and hypomethylation in GAC and hypermethylation in CAC were negatively correlated with microsatellite instability. Additionally, the hypo- and hyper-methylated site-based signatures with high accuracy, high efficiency and strong independence can separately predict the OS of GAC and CAC patients. By integrating the methylation-based signatures with prognosis-related clinicopathologic characteristics, two clinicopathologic-epigenetic nomograms were cautiously established with strong predictive performance and high accuracy. Our research indicates that methylation mechanisms differ between GAC and CAC, and provides novel clinical biomarkers for the diagnosis and treatment of GAC and CAC.

<p>The Preoperative Enhanced Degree of Contrast-enhanced CT Images: A Potential Independent Predictor in Gastric Adenocarcinoma Patients After Radical Gastrectomy</p>

AimTo discover the value of contrast-enhanced CT parameters in predicting the prognosis of gastric adenocarcinoma (GAC) patients after radical gastrectomy.MethodsThe patients with a clinical diagnosis of GAC were retrospectively enrolled. Two radiologists drew the regions of interest (ROIs) in CT images and measured the CT attenuate value (CAV) in each phase and the corrected CAV (cCAV) in each contrast-enhanced phase. Patients were divided into two groups (high/low-enhancement) according to receiver operating characteristic (ROC) curve. Kaplan–Meier curve and Cox proportional hazards regression analysis were performed to evaluate correlation between prognosis and variables. Subgroup analysis was used to further analyze the prognostic value of variables.ResultsIn total 435 patients were included. According to ROC curve, the cCAV in delayed phase (DP-cCAV) with maximum AUC and Youden index was chosen. A total of 312 patients (71.7%) entered DP-cCAVlow group and remaining 123 (28.3%) patients were in DP-cCAVhigh group. According to univariate (high vs low, HR=2.120, p<0.001) and multivariate (high vs low, HR=1.623, p<0.001) Cox regression analysis, the low-enhancement state was considered as an independent protective factor. Subgroup analysis was based on age, maximum diameter of tumor, differentiation, vascular invasion status, and TNM staging. In most subgroups, the overall survival (OS) of DP-cCAVlow group was overwhelmingly satisfactory (all HR >1, expect TNM stage I, IV and differentiated type subgroups).ConclusionThe prognostic effectiveness of CT parameters as biomarkers for OS in GAC patients treated with radical gastrectomy has potential value.

Comparative effectiveness of treatment modalities in non-metastatic gastric adenocarcinoma: a propensity score matching analysis of the National Cancer Database

BackgroundWhile addition of chemotherapy and radiation to surgery improves the outcomes of non-metastatic gastric adenocarcinoma (GAC), the best treatment strategy remains controversial.MethodsTo determine the effectiveness of different strategies in patients...

Association of Foxp3 rs3761548 polymorphism with cytokines concentration in gastric adenocarcinoma patients

T regulatory cells (Tregs) and related-cytokines are effectively engaged in the process of tumor immune escape and functionally inhibit immune response against the tumor. This study aimed to investigate the association of Foxp3 gene single nucleotide polymorphism (SNP) (rs3761548) with serum IL-35, IL-10, and TGF-β levels in gastric adenocarcinoma (GA) patients. The blood samples were obtained from 150 GA patients and 166 control subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was done to genotyping of Foxp3 gene polymorphism (rs3761548). The serum cytokines levels were measured using the ELISA method. According to genotyping, the AA, and AC genotypes and A allele demonstrated significantly greater risk of GA. Considering the Lauren classification, our results revealed a greater risk of GA progression in patients with AC + AA genotype compared to CC genotype. Moreover, significantly increased levels of IL-10, IL-35, and TGF-β were observed in GA patients compared to controls and also in diffuse-type compared to the intestinal type of GA patients. The IL-35, IL-10 concentrations in GA patients displayed significant differences between the participants with CC, AC and AA genotypes. Further analysis indicated the prognostic role of serum IL-35, IL-10, and TGF-β levels in GA patients. Our results confirmed that the Foxp3 polymorphism (rs3761548) could influence the predisposition to GA and the serum IL-10, IL-35, and TGF-β levels. Thus, this polymorphism might be involved in the GA progression through influencing Tregs function and the secretion of immunomodulatory cytokines.

The metastatic pattern of intestinal and diffuse type gastric carcinoma – A Dutch national cohort study

IntroductionThe Lauren classification of gastric adenocarcinoma describes three histological subtypes, the intestinal, the diffuse and the mixed type carcinoma. The metastatic pattern of gastric adenocarcinoma by histological subtype has not been studied. MethodsGastric adenocarcinoma patients with metastatic disease at the time of diagnosis between 1999 and 2017 were identified through the Netherlands Cancer Registry. The Lauren classification was determined based on pathology reports archived in the Dutch Pathology Registry and was linked to individual cases in the Netherlands Cancer Registry. ResultsAmong 8 231 newly diagnosed, metastatic and evaluable gastric adenocarcinoma patients, 57 % had an intestinal type carcinoma, 38 % patients had a diffuse type carcinoma and 5 % had a mixed type carcinoma. Intestinal type carcinomas more often metastasized to the liver (57 % versus 21 %, p < 0.0001) and lungs (13 % versus 7 %, p < 0.0001), whereas diffuse type carcinomas more often metastasized to the peritoneum (58 % versus 29 %, p < 0.0001) and bones (9 % versus 6 %, p < 0.0001). Patients with a diffuse type carcinoma had a worse survival perspective regardless of the number or the location of the metastases. ConclusionIn this national cohort study, metastatic gastric adenocarcinoma of the intestinal type had a predilection for the liver and that of the diffuse type for the peritoneum.

Prognostic factors for survival in patients with gastric adenocarcinoma.

BackgroundGastric cancer ranks as a leading cause of cancer deaths worldwide. Information of prognostic factors related to gastric cancer are limited.AimThis study aimed to gather clinical data and prevalence of prognostic factors related to gastric adenocarcinoma in Thailand.Methods and resultsThis retrospective cohort study was conducted at Thammasat University Hospital, Thailand between January 2010 and July 2018. Gastric adenocarcinoma patients were enrolled and followed up for at least 5 years. Total of 210 gastric tumor patients were enrolled. One hundred patients were diagnosed with gastric adenocarcinomas (57 men and 43 women, mean age = 61.1 years). The leading presenting symptoms were weight loss (65%), followed by dyspepsia (54%) and UGI bleeding. Common clinical manifestations were thrombocytosis (26%), followed by syndrome of inappropriate antidiuretic hormone (SIADH; 15%). Eosinophilia was present in early cancer (25.0% vs 6.5%, P = .123), while SIADH and thrombocytosis were more common in advanced stages (16.3% vs 0%, P = .602, and 28.3% vs 0%, P = .108, respectively). SIADH was significantly related to reduced 1‐year survival rate compared to normal serum sodium levels (21.4% vs 71.4%, OR 0.109, 95% CI 0.024‐0.497, P = .004). Five‐year survival rates were worse in patients with SIADH, but better in patients with eosinophilia compared to patients without these conditions (0% vs 27.8%, P = .058 and 20.0% vs 7.8%, P = .375, respectively).ConclusionThrombocytosis and SIADH were common in gastric cancer. SIADH was significantly correlated with poor 1‐year survival. These clinical manifestations might be useful for predicting gastric cancer prognosis.

LncRNA PVT1 Is a Poor Prognosticator and Can Be Targeted by PVT1 Antisense Oligos in Gastric Adenocarcinoma.

Simple SummaryLncRNA-PVT1 is upregulated in a variety of human cancers, to validate LncRNA-PVT1 expression in gastric adenocarcinoma (GAC), RNA-SCOPE of LncRNA-PVT1 was performed in a large cohort in GAC TMAs. LncRNA-PVT1 is upregulated in GAC tissues and correlated with larger tumor size, invasion depth and lymph node metastasis. In the peritoneal metastasis ascites cells of GAC, LncRNA-PVT1 level is also upregulated compared to normal adjacent tissues. LncRNA-PVT1 is a poor prognosticator as well as therapeutic target in GAC. Targeting PVT1 using PVT1 ASOs suppressed tumor proliferation and invasion in both vitro and vivo, thus provide a novel therapeutic strategy for GAC.Gastric adenocarcinoma (GAC) is inherently resistant or becomes resistant to therapy, leading to a poor prognosis. Mounting evidence suggests that lncRNAs can be used as predictive markers and therapeutic targets in the right context. In this study, we determined the role of lncRNA-PVT1 in GAC along with the value of inhibition of PVT1 using antisense oligos (ASOs). RNA scope in situ hybridization was used to analyze PVT1 expression in tumor tissue microarrays (TMAs) of GAC and paired normal tissues from 792 patients. Functional experiments, including colony formation and invasion assays, were performed to evaluate the effects of PVT1 ASO inhibition of PVT1 in vitro; patient-derived xenograft models were used to evaluate the anti-tumor effects of PVT1 ASOs in vivo. LncRNA-PVT1 was upregulated in GACs compared to the matched adjacent normal tissues in the TMA. LncRNA PVT1 expression was positively correlated with larger tumor size, deeper wall invasion, lymph node metastases, and short survival duration. Inhibition of PVT1 using PVT1 ASOs significantly suppressed tumor cell growth and invasion in vitro and in vivo. PVT1 expression was highly associated with poor prognosis in GAC patients and targeting PVT1 using PVT1 ASOs was effective at curtailing tumor cell growth in vitro and in vivo. Thus, PVT1 is a poor prognosticator as well as therapeutic target. Targeting PVT1 using PVT1 ASOs provides a novel therapeutic strategy for GAC.

A Prospective Study of Etiology and Clinical Presentation of Gastric Adenocarcinoma

Background: Dietary factors, Smoking, Alcohol, H. Pylori all have been linked to gastric carcinoma andmost of them are modifiable which can reduce the risk of cancer hence this study was undertaken to studythe etiology of gastric adenocarcinoma and its clinical presentation.Methodology: This was a prospective study in which 50 patients of gastric adenocarcinoma admitted in thesurgery department at a tertiary hospital were studied.Results: Out of 50 patients studied, 36 were males and 14 were females. The risk factors like H. pyloribiopsy, heredity, salt and preserved food were found less in the cancer patients while alcohol was found to bemore in them. Smoking was present equally in both the groups. Vomiting (100%) and loss of weight (100%)were the most common presenting feature. 46% had a Karnofsky score more than 80.Conclusion: Alcohol is a risk factor for gastric adenocarcinoma and loss of weight and vomiting are commonclinical presentation.

Surgery for Gastric Adenocarcinoma with Hospital Stay: A Prospective Study

Background: With the new changing lifestyles and the control if infectious diseases, cancer is soon emergingto be one of the leading causes of deaths in developing countries like India. Surgical procedure showsimprovement in survival period for a patient at stage II and III after correcting the nutritional status of thepatients. There is a decline in post-operative complication with patients who underwent surgery. Hence thisstudy was undertaken to study the curative and palliative surgeries in the patients of gastric adenocarcinomaand their hospital stay.Methodology: This was a prospective study in which 50 of gastric adenocarcinoma patients who wereadmitted in the surgery department at Datta Meghe Medical College, Shalinitai Meghe Hospital and ResearchCentre, Nagpur in collaboration with Jawaharlal Nehru Medical College, Datta Meghe Institute of MedicalSciences, Sawangi Meghe, Wardha, Maharashtra were studied.Results: Majority of patients presented with Stage II (88%) while 12% presented with stage III. 82% patientsunderwent curative surgeries while 18% underwent palliative surgeries. The duration of hospital stays forGastric Adenocarcinoma surgery for Stage II ranges from 6-8 days (median 7 days) whereas for Stage IIIit is 7-8 days (median 7.5 day). A total of 50 patients who underwent surgery for histologically provengastric adenocarcinoma. Out of 50 patients a majority i.e. 88% presented in stage II while 12% presented instage III.Conclusion: On the basis of our observations we concluded that the patients presenting earlier in stage IIundergo curative surgeries most often and mean hospital stay post-surgery around a week.

Circ_0000260 Regulates the Development and Deterioration of Gastric Adenocarcinoma with Cisplatin Resistance by Upregulating MMP11 via Targeting MiR-129-5p.

BackgroundCisplatin (CDDP) plays a vital role in the treatment of advanced gastric adenocarcinoma (GAC); however, the development of chemoresistance depletes the overall benefit of CDDP. This study harbored the aim to investigate the role of a novel circular RNA (circRNA), circ_0000260, in DDP-resistant GAC and provide a potential mechanism to explain its function.MethodsThe morphology of tumor tissues and normal tissues was observed by hematoxylin-eosin (HE) staining. The isolated exosomes were observed and examined using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The expression of circ_0000260, miR-129-5p and matrix metalloproteinase 11 (MMP11) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CD63, CD81, fibronectin, vitronectin and MMP11 were detected by Western blot. Cell viability, colony formation, cell apoptosis, migration, invasion and cell adhesion were monitored by cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry assay, scratch assay, transwell assay and cell adhesion assay, respectively. The interaction between miR-129-5p and circ_0000260 or MMP11 predicted by bioinformatics analysis was verified by dual-luciferase reporter assay. Animal experiments were performed in nude mice to explore the role of circ_0000260 in vivo.ResultsThe expression of circ_0000260 was promoted in tumor tissues and serum-derived exosomes of GAC patients, and circ_0000260 expression in CDDP-resistant tumor tissues was higher than that in CDDP-sensitive tumor tissues. Circ_0000260 knockdown lessened CDDP chemoresistance, suppressed cell proliferation, migration, invasion and adhesion, and induced apoptosis. In mechanism, circ_0000260 regulated the expression of MMP11 by targeting miR-129-5p. MiR-129-5p inhibition could reverse the functions of circ_0000260 knockdown, and MMP11 knockdown could also reverse the effects of miR-129-5p inhibition. Besides, circ_0000260 knockdown attenuated CDDP resistance during tumor growth in vivo by regulating the expression of miR-129-5p and MMP11.ConclusionCirc_0000260 regulated CDDP chemoresistance of GAC by promoting MMP11 expression via targeting miR-129-5p.

Oncogenes Orchestrate Immunosuppressive Stroma in Gastric Adenocarcinoma

Gastric adenocarcinoma (GAC) is among the three most common cancers in the world. The majority of GAC patients are diagnosed in an advanced stage and have a median survival of ~9 months. There are limited effective therapeutic strategies available in the clinic and currently U.S. Food and Drug Administration (FDA) approved immune therapy is programmed death-1 (PD-1) antibodies (e.g. pembrolizumab) but only a few patients seem to benefit. Transformation to cancer occurs when multiple genes and cellular pathways are dysregulated in multi-cellular organisms. Mounting evidence supports that oncogenes orchestrate tumor immune suppressive stroma to foster tumor favoring microenvironmental niche. Thus, deeper understanding of the immunosuppressive mechanisms in tumor stroma especially orchestrated by notable oncogenes can allow exploration of novel avenues that may have an impact on patient outcome. In this review, we summarize current progress of notable oncogenes and pathways including Ras/Myc, EGFR/HER2, PI3K/mTOR, Wnt/β-catenin, and Hippo/YAP pathways focusing on the interplay between these oncogenic pathways and immunosuppressive stroma. Future potential novel targets and immune checkpoint blockage are discussed.

Comparative Study of Clinico-Pathological Profiles of Patients with Proximal Versus Distal Gastric Adenocarcinoma

Background: Stomach adenocarcinoma has been a major source of malignant development through the greater part of the 20th century. In different parts of the world, the prevalence of this disease has decreased, mostly due to changes in diet and some other natural constituents.&#x0D; Aim: To examine the clinical pathology of patients with proximal and distal gastric adenocarcinomas.&#x0D; Methodology: This was the prospective work carried out with gastric adenocarcinoma patients treated at Sree Balaji Medical College and Hospital (SBMCH), Chennai, Tamilnadu, India. All patients were undergone upper gastrointestinal endoscopy and an imaging. In endoscopy, biopsies will be taken from the lesion and biopsies were subjected to histopathological examination.&#x0D; Results: The most striking epidemiologic perceptions were the increasing frequency of adenocarcinomas of the proximal stomach and distal throat. We found that the occurrence of proximal gastric adenocarcinomas isn't expanding in our populace when contrasted with the rising rate of such proximal tumors in the Western Hemisphere.&#x0D; Conclusion: In our investigation distal gastric adenocarcinomas were a more incessant finding than the proximal gastric adenocarcinomas.

Comparison of overall survival of gastric neoplasms containing neuroendocrine carcinoma components with gastric adenocarcinoma: a propensity score matching study

BackgroundGastric neoplasms containing neuroendocrine carcinoma (NEC) components are rare malignancies with highly aggressive behavior and a poor prognosis and include pure NEC and mixed tumors containing NEC components. We aimed to investigate whether there is a distinct difference in overall survival (OS) between gastric neoplasms containing NEC components and gastric adenocarcinoma.MethodsSurgically resected gastric neoplasms containing NEC components (n = 180) and gastric adenocarcinomas (n = 785) from January 2013 to December 2019 at Peking University Cancer Hospital were retrospectively analysed. Patients were categorized into a surgical group and a neoadjuvant group and adjusted using propensity score matching. In the two groups, gastric neoplasms containing NEC components were divided into pure NEC and mixed tumors with less than 30% (< 30% G-HMiNEN), between 30 and 70% (G-HMiNEN) and more than 70% (> 70% G-HMiNEN) neuroendocrine carcinoma components. OS was compared between these groups and the gastric adenocarcinoma group.ResultsThe OS of gastric neoplasms containing neuroendocrine NEC components was poorer than that of gastric adenocarcinomas in the surgical group, regardless of whether the percentage of neuroendocrine cancer components was less than 30%, between 30 and 70%, more than 70% or 100%. Cox multivariable regression analysis suggested that tumor category (neoplasms containing NEC components or gastric adenocarcinoma) was an independent risk factor for prognosis. Interestingly, among patients receiving neoadjuvant therapy, the difference was not significant.ConclusionsGastric neoplasms containing any proportion of NEC components had poorer overall survival than gastric adenocarcinoma in patients treated with surgery directly, indicating that these neoplasms are more malignant than gastric adenocarcinoma. Among the patients receiving neoadjuvant therapy, the difference in overall survival was not significant, which was in sharp contrast with the results of the surgery group, suggesting that neoadjuvant therapy may have a good effect in the treatment of these neoplasms.

Abstract 6481: Clinical Association of Siclec15 in gastric adenocarcinomas patients

Abstract The identification of novel biomarkers for diagnosis and prognosis of Gastric Cancer (GC) is pivotal to reduce disease-associated mortality. Previous studies have reported that Siglec-15 is overexpressed on human cancer, including colon, thyroid, lung, liver. The Siglecs are a group of sialic-acid-binding immunoglobulin-like lectins, involved in cell-cell and cell-pathogen interactions. Recently, it was reported that Siglec-15 could be a potential target for cancer immunotherapy, because it supresses T cell activity and its expression with PD-L1 are mutually exclusive. However, the relationship between the expression of Siglec-15 in GC pathological and outcome parameters were not investigated. Therefore, the purpose of this study was to evaluate the expression of SIGLEG15 in gastric adenocarcinomas patients and correlated the expression patterns with each other and with some clinicopathological variables. Surgical specimens of GC tissue and adjacent normal mucosa obtained from 67 patients were examined. The patients underwent gastrectomy at the Hospital do Cancer de Pernambuco, Brazil, between 2013 and 2016. Informed consent was obtained from each patient, with all protocols approved by the ethics committee's (CAAE: 39976214.90000.5205). Protein expression was examined by immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded (FFPE) specimens. The primary anti-SIGLEC15 antibody were used and positive control was performed on a tissue model indicated on the data sheet and reference sources (The Human Protein Atlas). Samples that demonstrated enzyme staining in more than 10% of the neoplastic cells in different degrees of intensity were considered positive and those that did not present were negative. Of 67 GC patients, 52 (77.61%) were SIGLEC-15 positive and 15 patients (25.38%) were negative. In 40 samples (59.70%) of the 67 patients analysed presented an adjacent normal tissue, in which 14 (35%) were SIGLEC-15 positive, specially in productions cells of the gastric glands and in the ducts. In neoplastic lesions, SIGLEC-15 was observed in the cytoplasm in 13 samples (19.40%), perinuclear in 4 (5.97%) and nuclear in 1 only sample (1.49%). On the other hand, combinations of cytoplasmic, nuclear and perinuclear staining were observed in 44 samples (61.9%). Expression of SIGLEC-15 was significantly associated with age (p=0.047), with tumor differentiation (p=0.002), angiolymphatic invasion (p=0.02) and surgical staging (p=0.056). Additional analysis, including sex, type of surgery, initial treatment, nodal status, radiotherapy, chemotherapy, lymph node, H.Pylory infection and overall and disease-free survival were not significant. High Siglec-15 expression in gastric cancer could be a novel biomarker for surgical staging and vascular invasion. Further studies with a larger group of patients and experimental assays are required to elucidate Siglec-15 role in gastric cancer. Citation Format: Michelly Cristiny Pereira, Michael Williames Quirino, Antônio Felix Silva Filho, Mário Rino Martins, Maira Galdino da Rocha Pitta, Moacyr Jesus Barreto de Melo Rego. Clinical Association of Siclec15 in gastric adenocarcinomas patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6481.

Abstract 3632: Genomic profiling in circulating tumor DNA from Chinese advanced gastric adenocarcinomas patients

Abstract Background and Objective: Circulating tumor DNA (ctDNA) is considered to be an ideal sample for advanced unresectable cancer patients to perform gene sequencing to guide clinical therapy, which might help to avoid tumor heterogeneous, especially in gastric adenocarcinomas (GACs). However, the ctDNA genomic profiling of Chinese advanced GACs is still missing. Methods: Blood samples were obtained from 122 advanced GACs patients. Target sequencing were performed on ctDNA using a validated commercial 150-gene-panel NCC-GP150, which includes 100 microsatellite loci. Blood tumor mutation burden (bTMB) and blood microsatellite instability (bMSI) were calculated according to the NGS results. Statistical analysis was performed by the Mann-Whitney U test and Fisher exact test using GraphPad Prism. Results: In 122 patients, 47 (38.5%) were female and 75 (61.5%) were male, with the median age of 61 (range 24 to 84). A total of 660 somatic variations were identified in 118 genes as indicated by a maximum somatic allele frequency (MSAF) of &amp;gt;0.3%. One hundred and two (83.6%) patients carried at least one somatic variation and 84 (68.9%) patients had at least on pathogenic or likely pathogenic variations. The median pathogenic or likely pathogenic variations was 2.5 per patient in our cohort. The most frequent altered genes were TP53 (36.9%), LRP1B (18%), MYC (14.8%), RBM10 (13.9%), ERBB2 (13.9%), KRAS (12.3%), AR (11.5%) and FAT1 (10.7%). From the perspective of signaling pathway, the variations occurred frequently in RTK-Ras-MAPK pathway (53.3%), cell cycle pathway (52.5%), DNA damage repair (DDR) pathway (22.1%), Wnt pathway (18.9%), PI3K/AKT pathway (16.4%), and TGF-β pathway (2.5%). The median bTMB was 3 (mean 5.27, range 0 to 52); and 8 (7.8%) patients had high bMSI. The bMSI-H patients had significantly higher bTMB than bMSS patients (22 vs 3, p&amp;lt;0.0001) and patients harboring DDR pathway gene variations had significantly higher bTMB than wildtype subgroups (6 vs 3, p=0.0004). Conclusions: Our study revealed a comprehensive genomic profiling of advanced Chinese GACs patients. And the relationship between the genomic profiling and target-therapy as well as immunotherapy will be studied in an enlarged group of GACs patients. Citation Format: ZHE ZHANG, Hui Chen, Yifan Zhou, Bei Zhang, Yuezong Bai, Lieping Guo. Genomic profiling in circulating tumor DNA from Chinese advanced gastric adenocarcinomas patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3632.

Study of Location and Staging of Tumours in Patients of Gastric Carcinoma at a Tertiary Hospital

Cancer is also known as the captain of death for humanity. It ranks second only after heart disease leading to death worldwide. In India, the incidence of gastric cancer is considered low and variable in different parts of the world. Gastric carcinoma plays an essential role in determining its management also its location gives some idea about the etiopathogenesis; hence this study was undertaken to study the situation and staging of tumours in patients of gastric carcinoma. This was a prospective study in which 50 patients of gastric adenocarcinoma admitted in the department of surgery at a tertiary hospital were studied. Out of 50 patients studied, 36 were males, and 14 were females. Even though the mean age for male patients is slightly higher than female patients (62 versus 60), the most common location of the tumour was the antrum (88%) followed by the cardia (6%) while the body had just 4% of the tumours and 2% of the tumours were diffused. The most common stage for tumours was stage II (88%), followed by stage III (12%). There were no tumours in stage 1 and IV. Most patients were males who presented in early-stage II with antrum being the most common location of the tumour.

Tumor Regression Grade Predicts Survival in Locally Advanced Gastric Adenocarcinoma Patients with Lymph Node Metastasis.

Background Tumor regression grade (TRG) is widely used in gastrointestinal carcinoma to evaluate pathological responses to neoadjuvant chemotherapy (NCT), but whether it is an independent prognostic factor is still controversial. The aim of this study is to investigate the value of TRG in locally advanced gastric adenocarcinoma patients who underwent NCT and curative resection. Methods Pathological regression was reevaluated according to the Mandard TRG. Survival curves were obtained by the Kaplan–Meier method, and differences in overall survival (OS) and disease-free survival (DFS) were compared using the log-rank test. Univariate and multivariate analyses for survival were based on the Cox proportional hazards method. Results In total, 290 patients were identified in our electronic database. In univariable analysis, TRG was associated with OS (HR = 3.822, P ≤ 0.001) and DFS (HR = 3.374, P ≤ 0.001). However, in multivariable analysis, TRG was not an independent factor for OS (P = 0.231) or DFS (P = 0.191). In the stratified analysis, TRG retrieved prognostic significance in patients with the metastasis of lymph node (HR = 2.034, P = 0.035 for OS; HR = 2.220, P = 0.016 for DFS), while not in patients with negative lymph node (P = 0.296 for OS; P = 0.172 for DFS). Conclusions TRG was not an independent predictor for survival, but the system regained its predicting significance in patients with lymph node metastasis.