Significance of Serum Pepsinogens as a Biomarker for Gastric Cancer and Atrophic Gastritis Screening: A Systematic Review and Meta-Analysis

Background

Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection.

Methods

We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I² statistics and publication bias was assessed using Begg and Mazumdar’s test. Meta-regression and subgroup analyses were performed to explore study heterogeneity.

Results

In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60–0.76), 0.73 (95% CI: 0.62–0.82), 2.57 (95% CI: 1.82–3.62), and 0.43 (95% CI: 0.34–0.54), 0.76 (95% CI: 0.72–0.80) and 6.01 (95% CI: 3.69–9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55–0.80), 0.88 (95% CI: 0.77–0.94), 5.80 (95% CI: 3.06–10.99), and 0.35 (95% CI: 0.24–0.51), 0.85 (95% CI: 0.82–0.88) and 16.50 (95% CI: 8.18–33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66–0.75), specificity of 0.79 (95% CI: 0.79–0.80), DOR of 6.92 (95% CI: 4.36–11.00), and AUC of 0.78 (95% CI: 0.72–0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51–0.60), specificity of 0.79 (95% CI: 0.76–0.82), DOR of 6.88 (95% CI: 2.30–20.60), and AUC of 0.77 (95% CI: 0.73–0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52–0.83), specificity of 0.84 (95% CI: 0.68–0.93), DOR of 11.51 (95% CI: 6.14–21.56), and AUC of 0.83 (95% CI: 0.80–0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72–0.85), specificity of 0.89 (95% CI: 0.85–0.93), DOR of 24.64 (95% CI: 6.95–87.37), and AUC of 0.87 (95% CI: 0.81–0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38–0.54), specificity of 0.93 (95% CI: 0.91–0.95), DOR of 19.86 (95% CI: 0.86–456.91), and AUC of 0.86 (95% CI: 0.52–1.00).

Conclusion

SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future.     

胃癌与萎缩性胃炎的血清拉曼光谱数据分析

利用激光诱导拉曼光谱技术,测定了萎缩性胃炎患者、胃癌患者血清的拉曼光谱。采用主成分分析法和判别分析法对拉曼光谱数据进行了分析和处理,得到辨别胃癌和萎缩性胃炎的准确率为92％。     

Gene Polymorphisms of Micrornas in Helicobacter pylori-Induced High Risk Atrophic Gastritis and Gastric Cancer

Background and aims

MicroRNAs (miRNAs) are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC) and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of GC or high risk atrophic gastritis (HRAG) in European population.

Methods

Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281) of European descent. MiR-27a T>C (rs895819), miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913), miR-492 G>C (rs2289030) and miR-608 C>G (rs4919510) SNPs were genotyped by RT-PCR.

Results

Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR) - 1.46, 95% confidence interval (CI) 1.03-2.07, P = 0.032). MiR-608 GG genotype was more frequent in GC when compared to controls (OR −2.34, 95% CI 1.08–5.04), but significance remained marginal (P = 0.029). A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14–5.22, P = 0.021). The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC.

Conclusions

Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European subjects.     

慢性多灶萎缩性胃炎患者胃酸分泌与Hp感染及血清胃泌素的关系

目的:探讨多灶萎缩性胃炎(BAG)患者胃酸分泌与幽门螺杆菌(HP)感染及血清胃泌素水平的关系。方法:根据病理结果将60例确诊的慢性BAG患者分为轻度、中度、重度BAG组,监测各组患者24小时胃内PH值的变化、血清胃泌素水平及HP感染情况。结果:随着萎缩程度的加重,HP阳性率、胃内中位PH值及算数均数p H值逐渐升高,血清胃泌素水平逐渐降低;轻度、中度、重度BAG组组间中位p H值、算数均数p H值及血清胃泌素水平比较有显著差异(均P0.05);重度BAG组HP感染与轻度组、中度组比较有统计学差异(均P0.05),而轻度组HP感染与中度组差异无统计学意义(P0.05)。结论:随着慢性BAG萎缩程度的加重,HP阳性率和p H值逐渐升高,血清胃泌素水平逐渐降低。HP感染、胃泌素水平及胃酸分泌水平三者相互影响,相互作用。     

血清胃蛋白酶原联合G-17对萎缩性胃炎及胃癌早期诊断价值

目的:探索检测血清胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PGⅡ)、胃泌素-17(G-17)在萎缩性胃炎及胃癌中的诊断价值。方法:收集医院2015年2月至12月门诊及住院的慢性非萎缩性胃炎44例(非萎缩性胃炎组),慢性萎缩性胃炎47例(萎缩性胃炎组),早期胃癌42例(胃癌组)。采用酶联免疫吸附试验(ELISA)测定各组血清PGⅠ、PGⅡ、G-17的水平,同时计算PGⅠ/PGⅡ的比值(PGR),比较各组指标间的差异,同时绘制各指标筛查萎缩性胃炎及胃癌的受试者工作曲线(ROC)曲线,分别评价其诊断价值。结果:胃癌组及萎缩性胃炎组的血清PGⅠ、PGR水平较非萎缩性胃炎组明显下降,且胃癌组下降更明显,差异均具有统计学意义(P0.05),萎缩性胃炎组血清PGⅡ显著低于非萎缩性胃炎组,差异均具有统计学意义(P0.05);胃癌组的血清G-17水平较非萎缩性胃炎组及萎缩性胃炎组均升高,差异有统计学意义(P0.05)。血清PGⅠ筛查萎缩性胃炎的最佳界值为PGⅠ90 ng/m L,其灵敏度和特异度分别为71.5%和51.0%,血清PGR筛查萎缩性胃炎的最佳界值为PGR8,其灵敏度和特异度分别为71.9%和54.0%,血清G-17筛查萎缩性胃炎的最佳界值为G-175 pmol/L,其灵敏度和特异度分别为66.1%和64.0%。血清PGⅠ筛查胃癌的最佳界值为PGⅠ73 ng/m L,其灵敏度和特异度分别为86.0%和74.9%;血清PGR筛查胃癌的最佳界值为PGR3,其灵敏度和特异度分别为90.2%和62.5%;血清G-17筛查胃癌的最佳界值为G-174 pmol/L,其灵敏度和特异度分别为62.5%和61.3%。结论:胃癌及萎缩性胃炎患者血清PGⅠ、PGR水平下降明显,且胃癌患者的血清G-17异常升高,血清PG联合GS-17测定可用于萎缩性胃炎及胃癌的早期筛查。     

Serum Gastrin and the Antral Mucosa in Atrophic Gastritis

The gastric antral mucosa was studied histologically in 22 patients with atrophic gastritis, of whom 11 had high levels and 11 had normal levels of serum gastrin. The antrum was graded histologically from normal to grade 3 gastritis. All patients with hypergastrinaemia (nine seropositive and two seronegative for parietal cell antibody) had either a normal antrum or minimal (grade 1) antral gastritis. In contrast all but one patient without raised serum gastrin (nine seronegative and two seropositive for parietal cell antibody) had severe (grades 2-3) antral gastritis. Thus circulating gastrin levels observed in patients with gastritis and achlorhydria can be directly related to the presence or absence of antral mucosal damage.Comparison of the histological appearances of the antral mucosa with serum gastrin and parietal cell antibody status has provided a basis for the separation of two distinctive forms of atrophic gastritis.     

Identification of Serum Biomarkers for Gastric Cancer Diagnosis Using a Human Proteome Microarray

We aimed to globally discover serum biomarkers for diagnosis of gastric cancer (GC). GC serum autoantibodies were discovered and validated using serum samples from independent patient cohorts encompassing 1,401 participants divided into three groups, i.e. healthy, GC patients, and GC-related disease group. To discover biomarkers for GC, the human proteome microarray was first applied to screen specific autoantibodies in a total of 87 serum samples from GC patients and healthy controls. Potential biomarkers were identified via a statistical analysis protocol. Targeted protein microarrays with only the potential biomarkers were constructed and used to validate the candidate biomarkers using 914 samples. To provide further validation, the abundance of autoantibodies specific to the biomarker candidates was analyzed using enzyme-linked immunosorbent assays. Receiver operating characteristic curves were generated to evaluate the diagnostic accuracy of the serum biomarkers. Finally, the efficacy of prognosis efficacy of the final four biomarkers was evaluated by analyzing the clinical records. The final panel of biomarkers consisting of COPS2, CTSF, NT5E, and TERF1 provides high diagnostic power, with 95% sensitivity and 92% specificity to differentiate GC patients from healthy individuals. Prognosis analysis showed that the panel could also serve as independent predictors of the overall GC patient survival. The panel of four serum biomarkers (COPS2, CTSF, NT5E, and TERF1) could serve as a noninvasive diagnostic index for GC, and the combination of them could potentially be used as a predictor of the overall GC survival rate.Gastric cancer (GC)¹ is the second leading cause of cancer-related deaths. A total of 952,000 new GC cases (6.8% of the total of the new cancer case) and 723,000 deaths (8.8% of the total new cancer case) occurred in 2012 (1). The highest mortality rates have been reported in East Asia, including China, Japan, and Korea (2–4), and ∼60% of new GC cases and deaths worldwide occur in this region. As GC has a 5-year survival rate of less than 15%, accurate diagnosis and prognostic assessment of patients are essential for optimizing therapeutic strategies, predicting the outcome of treatment, extending the survival period of patients, and potentially healing to reduce cancer mortality (5).A variety of serum antigen biomarkers has been used for GC diagnosis and prognosis, e.g. carcinoembryonic antigen, carbohydrate antibody 19-9 (CA19-9), carbohydrate antibody 72-4 (CA72-4), and carbohydrate antibody 50 (CA50); the protein levels of these antigens in serum are usually used as signatures indicating cancer risk. However, generally, these serum antigen biomarkers lack sufficient sensitivity and specificity (6–8).Autoantibodies against proteins that result from abnormal gene expression and gene mutation in patients with various tumors represent another type of serum biomarker (9–12). The corresponding antigens of the autoantibodies are usually recognized as tumor-specific antigens or tumor-associated antigens (13–16). There is particular interest in these autoantibodies due to the potential diagnostic and prognostic applications of the autoantibodies and their corresponding antigens. Indeed, there is a need to identify novel autoantibody-based biomarkers to improve the sensitivity and specificity for the diagnosis of GC.In this study, we used a human proteome microarray containing 16,368 proteins to discover and independently validate serum autoantibodies with potential for diagnosis and prognosis of GC in a set of 1,401 serum samples. The samples were from 537 GC patients, 550 healthy controls, and 314 individuals of GC-related diseases. Four autoantigen serum biomarkers, COP9 constitutive photomorphogenic homolog subunit 2 (COPS2), CTSF, ecto-5′-nucleotidase (NT5E), and telomeric repeat binding factor 1 (TERF1), were identified with a combined diagnostic sensitivity of 95% and specificity of 92%. Furthermore, our data suggested COPS2, CTSF, NT5E, and TERF1 could also serve as potential predictors for prognostic assessment.     

High-risk Population for Gastric Cancer Development Based on Serum Pepsinogen Status and Lifestyle Factors

Background: Gastric atrophy is a major risk factor for non-cardiac gastric cancer. Serum pepsinogen status could identify people at high-risk for gastric cancer development during our previous cohort study. However, lifestyle-related factors may additionally affect this risk.
Materials and methods: A total of 6983 Japanese were followed up by annual endoscopy in the previous study, and 43 cases of gastric cancer including two cardiac cancers developed. In most subjects, the body length and weight were measured and a questionnaire was applied to gather information regarding life habits. The risk of non-cardiac gastric cancer development during surveillance was re-analyzed based on serum pepsinogen, sex, age, body mass index (BMI), alcohol, and smoking habit.
Results: A total of 6158 subjects with 37 non-cardiac gastric cancer development (male/female = 4259/1899, mean age = 49.0, mean follow-up period = 4.79 years) were entered into analysis. In a multivariate analysis, old age (by 10 years; (odds ratio) OR, 2.8; p  < .001), alcohol (weekly; OR, 2.4; p  = .03), smoking (current; OR, 5.6; p  = .006 and past; OR, 3.9; p  = .04), and pepsinogen status ("atrophic"; OR, 6.2; p  < .001) were independent risk factors, whereas BMI was not. The annual incidence of gastric cancer was 1.2% in the older subjects aged ≥ 60 years with "atrophic" pepsinogen status. Moreover, it was as high as 2.9% when they had both alcohol and current smoking habits.
Conclusions: Old age, alcohol, and smoking habits additionally promoted the risk for gastric cancer in subjects with gastric atrophy.     

EMT标志分子Vimentin在胃癌中的表达和临床意义

目的:探讨EMT标志分子Vimentin在胃癌中的表达和临床意义。方法:利用免疫组化染色的方法检测Vimentin在120例胃癌及其相应癌旁组织中的表达,统计分析Vimentin的表达水平与年龄、性别、组织学类型、TNM分期、淋巴结转移等临床病理特征间的相关性。结果:Vimentin在胃癌中的表达阳性率为55.8%,远高于相应癌旁组织的22.5%(P0.01),进一步分析研究发现Vimentin的表达水平在Ⅲ和Ⅳ期的胃癌中(TNM分期)的表达明显高于Ⅰ和Ⅱ期的胃癌,差异具有统计学意义(P=0.009),在发生淋巴结转移胃癌中表达明显高于未发生淋巴结转移的胃癌,差异具有统计学意义(P0.000)。结论:Vimentin在胃癌中高表达,其表达水平与TNM分期、淋巴结转移密切相关,提示Vimentin在胃癌的转移过程中可能发挥重要作用。     

微小RNA与胃癌的关系

微小RNA（microRNA、miRNA）与胃癌的发生发展可通过调控其靶基因参与的信号传导通路,影响胃癌的发生、侵袭和转移等过程,发挥着类似于癌基因或抑癌基因的作用。目前,已发现多种microR—NA与胃癌关系密切,包括通过调节周期蛋白依赖性蛋白激酶（Cdk）表达影响胃癌细胞增殖的miR-106b-93～25家族、miR-222—221家族和抑制高迁移率族蛋白A2（HMGA2）基因表达抑制胃癌细胞转移的miR-129和let-一7miRNA家族等。另有研究表明,miR-d21和miR-31检测阳性率显著高于血清CEA,可能成为新的胃癌肿瘤标志物。miR-15b和miR-16与胃癌多药耐药的关系也说明microRNA可能成为胃癌治疗新的靶点。     

PRR11在胃癌中的表达及其与预后的关系

检测PRR11蛋白在胃癌中的表达,分析其表达异常与胃癌临床指标及预后间的关系。用Western免疫印迹比较胃癌和正常组织中PRR11的表达。构建含167例胃癌的组织芯片,用免疫组化法检测PI汛11蛋白在胃癌组织中的表达,统计学分析其与肿瘤大小、肿瘤侵袭、组织分化、淋巴结转移、TNM分期及胃癌患者总生存期之间的关系。PRR11在胃癌组织中的表达高于癌旁组织,在胃癌中的表达率为50．9％（85／167）,而在癌旁黏膜中不表达或微弱表达。PRR11的表达与胃壁侵袭、淋巴结转移、疾病分期和组织分化呈正相关（P〈0．05）。单因素生存分析表明,PRRll蛋白阳性表达患者较阴性患者生存期短（45个月VS81个月,P〈0．001）。多因素生存分析也表明,PRR11蛋白阳性表达患者生存期短于阴性患者（95％CI：0．347～0．865,P=0．01）。高表达PRR11与胃癌的发生、进展及预后密切相关,是判断胃癌患者预后的重要指标之一。     

进展期胃癌根治术后早期复发的影响因素分析

目的:分析影响进展期胃癌根治术后早期复发的相关因素,为临床干预工作提供依据。方法:选取2009年6月至2012年7月本院收治的195例进展期胃癌患者作为研究对象,所有患者均接受胃癌根治术治疗,根据患者术后1年内复发与否将上述患者分为早期复发组(n=103)与对照组(n=92)。先后采用x2检验、非条件Logistic回归分析确定影响进展期胃癌根治术后早期复发的独立相关因素。结果:单因素分析发现,两组患者的肿瘤直径、Borrmann分型、Lauren分型、T分期、N分期、TNM分期、新辅助化疗、术后化疗等指标相比差异有统计学意义(P0.05),两组患者的性别、年龄、体质指数、肿瘤位置、分化程度、手术方式、腹腔镜手术等指标相比差异无统计学意义(P0.05)。非条件Logistic回归发现,N分期、TNM分期是影响进展期胃癌根治术后早期复发的独立危险因素,而新辅助化疗是独立保护因素。结论:进展期胃癌的N分期、TNM分期是其术后早期复发的独立危险因素,采取而新辅助化疗可降低进展期胃癌根治术后早期复发率。     

HMGB1在胃癌组织及细胞系中表达的研究

目的:近年来的研究表明,高迁移率族蛋白(1HMGB1)在肿瘤的发生及恶性演变过程中发挥重要作用,本研究旨在探讨HMGB1在胃癌组织、正常组织、胃癌细胞系SGC-7901、BGC-823、HGC-27、AGS及正常胃黏膜细胞系GES中表达情况。方法:免疫组织化学法检测HMGB1在32例可手术切除的胃癌患者组织标本(包括癌组织和正常组织)的表达情况;RT-PCR及Westren Blot检测HMGB1在胃癌细胞系SGC-7901、BGC-823、HGC-27、AGS及正常胃粘膜细胞系GES的m RNA及蛋白质表达。结果:胃癌组织HMGB1免疫组织化学染色评分高于正常组织(P0.05);RT-PCR结果显示SGC-7901、BGC-823、HGC-27、AGS、GES细胞系HMGB1 m RNA表达丰度均较高;Westren Blot检测发现胃癌细胞系SGC-7901、BGC-823、HGC-27中HMGB1蛋白水平显著高于胃癌细胞系AGS及正常胃粘膜细胞系GES。结论:HMGB1在胃癌组织及正常组织中的表达具有显著性差异。胃癌细胞系SGC-7901、BGC-823、HGC-27相对于其它胃细胞系存在HMGB1高表达,适合后续基因敲除分析工作。     

Genome Sequences of Three Helicobacter pylori Strains Isolated from Atrophic Gastritis and Gastric Ulcer Patients in China

Helicobacter pylori is a bacterial pathogen which can lead to several human gastric diseases. Here we describe the genome sequences of three strains isolated from atrophic gastritis and gastric ulcers patients in China. The data will permit genomic characterization of traits that may contribute to various gastric diseases.     

血清CA125 和OPN 联检在卵巢癌患者中的诊断价值

目的:探讨CA125和OPN联检在卵巢癌诊断中的应用价值。方法:以50例正常健康人为对照,对经组织病理学确诊的69例卵巢癌患者和54例卵巢良性肿瘤患者术前行血清CA125(放免法)和OPN(ELISA法)测定。比较二种血清标志物在正常人、卵巢良性肿瘤和卵巢癌病例中的表达水平。以正常人血清OPN均值±1.96S作为上下界,计算OPN临界值,大于临界值即为OPN阳性。血清CA125≥35 U/mL为阳性。比较三组病例中血清CA125和OPN单检及联检的灵敏度及特异性。比较二种血清标志物在卵巢癌及卵巢良性肿瘤的不同组织分型中的灵敏度。结果:卵巢癌组血清CA125和OPN的水平均显著高于正常对照组和卵巢良性肿瘤组(P<0.01),OPN临界值为27 ng/mL。在卵巢癌诊断中CA125、OPN检测的敏感度分别为66.7%和85.5%,二者联检的敏感度为95.7%。同时二者联检对浆液性囊腺癌、粘液性囊腺癌和子宫内膜样腺癌的敏感度分别为91.7%、70.0%和66.7%。结论:血清CA125和OPN是卵巢癌诊断的敏感性指标,二者联检可提高卵巢癌、特别是粘液性卵巢癌诊断的敏感度。     

胃癌前病变及胃癌的血清学生物标志物研究进展

胃癌是死亡率极高的恶性肿瘤.胃癌的早期诊断有助于发现并选择合适的治疗方案以降低其死亡率.近年来随着分子生物学技术的发展,血清学标志物以其创伤小,痛苦少而成了研究的重点.由于胃癌通常由一系列癌前疾病发展而来,因此与胃癌前病变各个阶段相关的血清学生物标志物的检测对于胃部肿瘤的早期诊断同样具有重要的临床意义.本文综述了目前胃癌前病变阶段及胃癌诊断相关的血清学生物标记物研究的最新进展.这些血清学标志物对于病情估计以及胃癌的早期诊断、组织分型及判断预后等都具有重要意义.     

胃复春和瑞巴派特联合治疗慢性萎缩性胃炎临床疗效观察

目的:观察胃复春和瑞巴派特联合治疗慢性萎缩性胃炎(CAG)的临床疗效,以探索更好的治疗慢性萎缩性胃炎的临床方法。方法:选择经胃镜检查符合慢性萎缩性胃炎患者150例,随机分为瑞巴派特组、胃复春组和联合治疗组各50例,联合治疗组给予胃复春和瑞巴派特,疗程均为l2周,观察治疗前后症状变化,并复查胃镜及活检进行组织病理学改善的评估。并考察联合治疗组治疗前后血液流变学变化。结果:组织病理学改善方面联合治疗组总有效率为92%,明显优于各组总有效率;症状改善方面联合治疗组优于瑞巴派特组和胃复春组,联合治疗组治疗前后血液流变学变化差异有统计学意义(P<0.01)。结论:联合应用胃复春和瑞巴派特可有效提高慢性萎缩性胃炎的临床疗效。     

Identification of miRNAs Expression Profile in Gastric Cancer Using Self-Organizing Maps (SOM)

In this paper, an unsupervised artificial neural network was implemented to identify the patters of specific signatures. The networkwas based on the differential expression of miRNAs (under or over expression) found in healthy or cancerous gastric tissues.Among the tissues analyzes, the neural network evaluated 514 miRNAs of gastric tissue that exhibited significant differentialexpression. The result suggested a specific expression signature nine miRNAs (hsa-mir-21, hsa-mir-29a, hsa-mir-29c, hsa-mir-148a,hsa-mir-141, hsa-let-7b, hsa-mir-31, hsa-mir-451, and hsa-mir-192), all with significant values (p-value < 0.01 and fold change > 5) thatclustered the samples into two groups: healthy tissue and gastric cancer tissue. The results obtained “in silico” must be validated ina molecular biology laboratory; if confirmed, this method may be used in the future as a risk marker for gastric cancerdevelopment.