In vitro and In silico Analysis of SCIN rs376349889 as a Potential Biomarker for Gastric and Colorectal Cancers.

Thyroglobulin gene is associated with premature ovarian failure

The development of targeted therapies for KRAS, EGFR and HER2 may increase the range of response in patients with colorectal cancer. Mutation at codons 12 and 13 of the KRAS gene has been shown to be predictive of cetuximab response in colorectal cancer. However, due to the combined effects of multiple oncogenes involved in disease progression of patients with colorectal cancer, it seems to be important to identify the molecular factors that characterize therapy-resistance phenotype of tumors. Forty six paraffin-embedded colorectal cancer specimens were analyzed for KRAS mutation and HER2 overexpression/amplification. A high–resolution melting (HRM) assay and single-nucleotide polymorphisms (SNPs) were used to detect somatic mutation in exon 2 notably condons 12 and 13 of the KRAS gene. HER2 overexpression was detected using monoclonal antibody and confirmed by fluorescence in situ hybridization (FISH) analysis. KRAS mutations for codons 12 and 13 were identified in 16/46 (34.7%) of patients by SNP. The alterations in KRAS gene were observed in similar percentage of both codons. Colorectal cancer showed mainly heterozygous 35G>A and 38G>A KRAS gene mutations. HRM analysis showed presence of KRAS exon 2 mutation in 13/46 (28.2%) colorectal cancers. Despite positive SPN results in three cases , HRM technique did not reveal KRAS gene alteration. The concordance rate between the two methodologies was high at 87.5%. KRAS mutation was more frequently observed in poorly differentiated tumors and adenocarcinomas than in other histological types. HER2 overexpression was found in 37/46 (80.3%) of all colorectal cancers and in 62.1%, 61.5% of KRAS mutation-positive cases detected by SNP and HRM techniques respectively. HER2 overexpression was accompanied by amplification of HER2 gene. The subgroup of colorectal cancers with KRAS mutation and HER2 overexpression/amplification was poorly differentiated. In summary, the presence of HER2 overexpression/amplification in KRAS mutation–positive colorectal cancers suggests a possible role for the use of specific tyrosine kinase inhibitors in the treatment of disease.

Although WAP four-disulfide core domain 2 (WFDC2) is widely recognized as a diagnostic biomarker for ovarian cancer, its function in other cancer types remains unclear. The aim of this study was to evaluate the prognostic potential of WFDC2 across multiple cancers. Publicly available transcriptomic datasets were analyzed to compare WFDC2 mRNA expression in normal and tumor tissues across various cancer types. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the association between WFDC2 mRNA expression and overall survival (OS). Plasma WFDC2 levels were measured using enzyme-linked immunosorbent assay in healthy donors as well as patients with gastric, lung, colorectal, esophageal, and pancreatic cancers. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of WFDC2. Kaplan-Meier analysis was conducted to evaluate the association between WFDC2 expression and OS. Cox proportional hazards regression analysis was performed to assess the prognostic significance of WFDC2 expression. WFDC2 mRNA expression was significantly elevated in gastric cancer, lung adenocarcinoma (LUAD), esophageal carcinoma, and pancreatic ductal adenocarcinoma (p < 0.01); however, it was significantly lower in colorectal cancer (p < 0.005). Kaplan-Meier analysis indicated that elevated WFDC2 mRNA expression in LUAD was only significantly associated with prolonged OS (p = 0.017), whereas no significant associations were observed in other cancer types. Moreover, plasma WFDC2 levels were significantly higher in all cancer patient groups than in healthy donors (p < 0.0001). ROC analysis revealed potential diagnostic performance, with an area under the curve of 0.890 (95% CI: 0.844-0.936) for distinguishing patients with cancer from healthy donors. Subgroup analysis indicated diagnostic performance across all cancer types. Elevated plasma WFDC2 levels were significantly associated with shorter OS in esophageal cancer (p = 0.0226). Multivariate Cox regression analysis confirmed that plasma WFDC2 concentration was an independent prognostic factor in gastric (HR = 1.04, 95% CI: 1.00-1.07, p = 0.019) and esophageal cancers (HR = 1.08, 95% CI: 1.02-1.13, p = 0.006). Plasma WFDC2 levels demonstrated potential diagnostic performance across multiple cancers and were significantly associated with poor prognosis in gastric and esophageal cancers.

Expectations for and challenges in population-based endoscopic gastric and colorectal cancer screening.

Carcinoembryonic antigen (CEA) is a common gastrointestinal tumor biomarker. Irisin is adipo-myokines that has been suggested to have a potential role in cancer development. However, limited studies test irisin as biomarker in gastric and colorectal cancers. Therefore, this study aims to investigate whether CEA and irisin could be a potential diagnostic biomarker in gastric and colorectal cancer. A case-control study consists of 90 subjects, 21 gastric cancer patients, 49 colorectal cancer patients and 20 control. Serum CEA was detected by fluorescence immunoassay (FIA) kit. Serum irisin was determined by enzyme-linked immunosorbent assay (ELISA) kit. Serum CEA increases significantly and serum irisin decreases significantly in gastric and colorectal cancer patients. According to Receiver Operating Characteristic (ROC) curve analysis, in gastric cancer, the area under curve of CEA is 1.00 (95% CI, 1.000-1.000, p< 0.0001). The diagnostic cut-off of CEA is< 3.08 ng/ml with %100 sensitivity and 100% specificity. The area under curve of irisin is 0.94 (95% CI, 0.8177-1.000, p< 0.0001). The cut-off of irisin is> 30.2 ng/ml with %90 sensitivity and 100%, specificity. In colorectal cancer, the area under curve of CEA is 0.99 (95% CI, 0.9866-1.000, p< 0.0001) and the diagnostic value< 2.6 ng/ml with %98 sensitivity and %100 specificity. The area under curve of irisin is 0.96 (95% CI, 0.9155-1.000, p< 0.0001). The diagnostic cut-off of irisin is> 41.9 ng/ml with 88.1sensitivity and 90.5 specificity. CEA and irisin could be powerful potential diagnostic biomarkers which would be use for early detection of gastric and colorectal cancers.

Background &amp; Aims: MicroRNAs (miRNAs) play a crucial role in diverse cellular biological processes such as differentiation, proliferation, migration, invasion and survival. MiRNA expression patterns are found to be frequently dysregulated in human tumors, which is currently being exploited both from a basic science perspective and for its clinical usefulness as disease biomarkers. Circulating miRNAs are attracting major interest as potential noninvasive biomarkers for colorectal cancer (CRC). This study aimed to identify a novel serum miRNA biomarker for the early detection and/or evaluating prognosis of CRC patients. Methods: Comprehensive miRNA array analysis was performed using serum samples from patients with colorectal neoplasia (CRC: n = 3, adenoma: n = 3) and healthy controls (n = 3). Next, to verify whether the candidate miRNA possessed a secretory potential, we screened miRNA expression levels in culture medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12 adenoma and 12 control subjects. Thereafter, we validated expression of candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects. Results: Through microarray analysis, we identified significantly higher levels of miRNA-1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We verified miR-1290 overexpression in serum of CRC patients in a training cohort. In the validation cohort, serum miR-1290 levels were significantly upregulated in patients with colorectal adenomas (P &amp;lt; 0.0001) and cancers (P &amp;lt; 0.0001). Serum miR-1290 levels could robustly distinguish adenoma (area under the curve [AUC] = 0.718) and CRC patients (AUC = 0.830) from normal subjects. Serum miR-1290 levels significantly diminished after surgical resection of the primary tumor in the same patients’ serum specimens (P &amp;lt; 0.0001). In addition, we observed a statistically significant positive correlation of miR-1290 expression levels between primary CRC tissues and matched serum samples (ρ = 0.482; P &amp;lt; 0.0001). High miR-1290 expression in serum and tissue was significantly associated with tumor aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an independent prognostic factor in CRC patients (hazard ratio = 4.51; 95% confidence interval = 1.23-23.69; P = 0.0096). Conclusions: Serum miR-1290, which might be secreted from primary CRC, is a novel diagnostic and prognostic biomarker in CRC. Citation Format: Yuji Toiyama, Hiroki Imaoka, Hiroyuki Fujikawa, Junichiro Hiro, Susumu Saigusa, Koji Tanaka, Yasuhiro Inoue, Yasuhiko Mohri, Takao Mori, Toshio Kato, Ajay Goel, Masato Kusunoki. Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 968.

We investigated whether four common microRNA polymorphisms (miR-146aC>G [rs2910164], miR-149T>C [rs2292832], miR-196a2T>C [rs11614913], and miR-499A>G [rs3746444]) are associated with the susceptibility and prognosis of gastric cancer in the Korean population. The four microRNA single-nucleotide polymorphisms (SNPs) were identified in a case-control study (461 patients; 447 controls) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in the Korean population. When patients were stratified into diffuse and intestinal-type gastric cancer groups, subjects with the miR-499AG and AG + GG genotypes had reduced adjusted odds ratios (AORs) for diffuse-type gastric cancer (AOR = 0.54 with 95% confidence interval [CI] = 0.31-0.97; AOR = 0.57 with 95% CI = 0.33-0.97). In the stratified analyses for gastric cancer risk, the miR-146aGG and CG + GG genotypes were associated with increased risk of gastric cancers among the non-smokers, whereas the miR-149TC and TC + CC genotypes showed lower risk of gastric cancer in males. The miR-196a2CC genotype was associated with elevated gastric cancer risk among females. For gastric cancer prognosis, intestinal-type gastric cancer patients with miR-146aCG + GG genotypes had significantly higher survival rates (log-rank P = 0.030) than patients with the CC genotype, and patients with the miR-499AA genotype had significantly increased survival rates compared to patients with the AG + GG genotypes (log-rank P = 0.013). When miR-146aCG + GG and miR-499AA genotypes were combined, the survival rate of intestinal-type gastric cancer patients was elevated (log-rank P < 0.001). No association was found between gastric or diffuse-type cancer prognosis and other miRNAs. Our data demonstrate that specific miRNA SNPs are associated with gastric cancer susceptibility (miR-499A>G) and prognosis (miR-146aC>G and miR-499A>G) in the Korean population depending on gastric cancer type.

MicroRNAs as Biomarkers in Colorectal Cancer

Single nucleotide polymorphisms (SNPs) located in long noncoding RNA CASC8 gene may influence the process of splicing and stability of messenger RNA conformation, resulting in the modification of its interacting partners. Genome-wide association studies have identified the SNP rs10505477 and SNP rs1562430 in CASC8 were associated with risk of the colorectal cancer (CRC) and breast cancer, respectively. In the present study, we genotyped the 940 surgically resected gastric cancer patients to explore the association between these two SNPs (e.g., rs10505477 and rs1562430) and survival of gastric cancer in a Chinese population. We found that the patients carrying rs10505477 GG genotype survived for a longer time than those with the GA and AA genotypes (log-rank P = 0.030). The similar result was also found in the dominant model (GA/AA vs GG, HR = 1.32, 95% CI = 1.08-1.63, log-rank P = 0.008). This risk effect was more pronounced among patients with tumor size ≤ 5 cm, diffuse-type gastric cancer, lymph node metastasis, no distant metastasis, and TNM stage III and IV. Furthermore, the area under the curve at five years was dramatically increased from 0.619 to 0.624 after adding the rs10505477 risk score to the traditional clinical risk score (TNM stage and lymph node metastasis). However, there was no association be found between the rs1562430 and the survival of gastric cancer. These findings suggested the SNP rs10505477 may contribute to the survival of gastric cancer and be a potential prognostic biomarker of gastric cancer.

Shotgun proteomics data analysis usually relies on database search. However, commonly used protein sequence databases do not contain information on protein variants and thus prevent variant peptides and proteins from been identified. Including known coding variations into protein sequence databases could help alleviate this problem. Based on our recently published human Cancer Proteome Variation Database, we have created a protein sequence database that comprehensively annotates thousands of cancer-related coding variants collected in the Cancer Proteome Variation Database as well as noncancer-specific ones from the Single Nucleotide Polymorphism Database (dbSNP). Using this database, we then developed a data analysis workflow for variant peptide identification in shotgun proteomics. The high risk of false positive variant identifications was addressed by a modified false discovery rate estimation method. Analysis of colorectal cancer cell lines SW480, RKO, and HCT-116 revealed a total of 81 peptides that contain either noncancer-specific or cancer-related variations. Twenty-three out of 26 variants randomly selected from the 81 were confirmed by genomic sequencing. We further applied the workflow on data sets from three individual colorectal tumor specimens. A total of 204 distinct variant peptides were detected, and five carried known cancer-related mutations. Each individual showed a specific pattern of cancer-related mutations, suggesting potential use of this type of information for personalized medicine. Compatibility of the workflow has been tested with four popular database search engines including Sequest, Mascot, X!Tandem, and MyriMatch. In summary, we have developed a workflow that effectively uses existing genomic data to enable variant peptide detection in proteomics.

The incidence of colorectal cancer (CRC) is increasing across the world, especially in younger age groups and the Indian subcontinent. Dysregulation in Notch pathway genes and their Single Nucleotide Polymorphism (SNPs) can potentially lead to aberrant signaling and contribute to CRC development. We investigated SNPs of Notch1 (rs3124591), Notch2 (rs10910779), Notch3 (rs1043994), and Notch4 (rs367398) in CRC (n = 103) and Controls (n = 103) along with their protein expression in the cases. The SNPs were detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method followed by Sanger sequencing. The protein expression was determined by the western blot technique. SPSS was used to analyze the correlations of the molecular findings with clinicopathological features and survival. The frequency of CT genotype in Notch1 was significantly lower in CRC patients compared to healthy controls (40.77% vs 62.14%; p = 0.009) and was associated with increased depth of invasion (p = 0.03). Notch3 polymorphism A > G showed significant association with the advanced TNM stage (p = 0.013). Interestingly, AG and GG genotype in Notch3 was significantly associated with increased protein expression (p = 0.047). The patients carrying the 'G' allele in Notch3 had an increased risk of having CRC (OR = 1.697, CI 95%: 1.001-2.873, p = 0.049) and a lower survival rate (p > 0.05). Notch4 polymorphism showed an association with tumor grade (p = 0.03). The genotypes CT and TT had lower survival rates than the CC genotype (p = 0.08). Notch receptor polymorphism, especially Notch3, is associated with increased protein expression and a higher risk of having CRC. Furthermore, poor survival in patients with Notch3 and Notch4 polymorphism suggests their potential as prognostic biomarker in CRC.

e18810 Background: Breast, stomach and colorectal cancers have high incidence in Colombia. Official cancer incidence registries depend upon sentinel site reports as there is no nationwide surveillance system. We aimed to identify administrative database algorithms for breast, stomach and colorectal cancer case selection and to compare their cancer incidence estimates to official registries. Methods: We conducted a systematic review to identify algorithms with high positive predictive values (VPP) for breast, stomach and colorectal cancer case identification in administrative databases. For each cancer we selected two algorithms: a sensitive algorithm, based on cancer-specific ICD-10 codes, and a specific algorithm, combining cancer-specific ICD-10 codes with at least one code for oncological procedures. We varied the number of months a cancer-specific ICD-10 code was registered within each algorithm to test for algorithm stability. We conducted a cohort study to estimate incident cancer cases for 2013 in four cancer sentinel cities in Colombia and one cancer reference center using both algorithms. We defined incident cases as cases lacking a cancer-specific ICD-10 code in the preceding two years and adjusted incident cases for type of regimen affiliation. Algorithms with results closest to official sources were selected as best performing algorithms. We used the contributive regimen Capitation Payment Unit administrative database of Colombia for 2011-2014 as source of information. Results: Breast cancer case-identification algorithms have a higher VPP reported in literature (83-100%) compared to colorectal (41.7-94%) and stomach cancer (35-59.7%) algorithms. The closest breast cancer incidence estimates to the official registries Infocancer and National Cancer Institute were yielded by the specific algorithm with ICD-10 codes persisting for four months (n= 672 vs 649 and 397 vs 212, respectively). The closest colorectal cancer cancer incidence estimates to official registries were yielded by the specific algorithm with ICD-10 codes persisting for three months (n= 219 vs 230 and 168 vs 139, respectively). The closest stomach cancer incidence estimates to official registries were yielded by the specific algorithm with ICD-10 codes persisting for one month (n= 122 vs 146 and 99 vs 153, respectively). Sensitive algorithms were less stable than specific algorithms across all three cancer types. Conclusions: Breast, stomach and colorectal incident cancer cases can be identified through administrative databases. VPP vary among types of algorithms and cancers. Specific algorithms provide better breast and colorectal incident cancer case-identification in Colombian administrative databases, compared to stomach cancer algorithms. This is a potential approach for estimating nationwide cancer incidence in Colombia.

digestive cancers (DC) are a group of cancers affecting the gastrointestinal tract and are capable of triggering an immune response. The cells produced during this response are tumor effectors whose role is to rid the body of tumor cells. The functional role of these cells, particularly the tumor-infiltrating lymphocytes (TILs), in the prognosis of patients remains poorly understood in Cameroon. This study aimed to evaluate the impact of lymphocyte infiltration on the survival of patients with certain digestive cancers. we conducted a retrospective cross-sectional study at the Oncology Department and the Anatomo-Cytopathology Laboratory of the Yaoundé General Hospital (YGH). Patients histologically diagnosed with colorectal and gastric cancers with available data from YGH between 2019 and 2023, who consented to participate and had a biopsy sample available at the YGH laboratory, were included in the study. Initially, we described patients' sociodemographic, clinical, and pathological characteristics. Then, we estimated the grade of lymphocyte infiltration in colorectal and gastric cancers using Hematoxylin-Eosin (HE) staining and analyzed the correlation between lymphocyte infiltration and patient survival through Cox regression. Data were analyzed with a significance level set at 5% for all comparisons. the study enrolled 90 patients with colorectal cancer and 50 with gastric cancer. Overall survival was 64.8% at 49 months in the study population, with the median not reached for colorectal cancer, and 64% at 39 months for gastric cancer, also with a median not reached. The average age at diagnosis for colorectal and gastric cancers was 54 ± 14.53 years and 53.24 ± 11.41 years, respectively. Men predominated in both pathologies, with a sex ratio of approximately 1.11. Colonic location was predominant (53%; 46/90) for colorectal cancer, with stage III disease being most common, while the antropyloric location (46%; 23/50) was predominant for gastric cancer, with stage IV being most frequent according to the AJCC. Moreover, 86% of patients had TILs in their histological samples, with a predominance of high TILs in both colorectal (38%; 34/90) and gastric (42%; 21/50) cancers. The performance of chemotherapy was inversely proportional to TILs in colorectal cancer, while no significant difference was found between TILs and chemotherapy in gastric cancer. However, no association was found between TILs and patient survival in either colorectal or gastric cancers. Patients who had metastases had a risk of death of 14.07 (aHR: 14.07, 95% CI 1.66-119.24; p = 0.015) compared with those who did not. Similarly, patients who had not taken chemotherapy had a 21.32 greater risk of death (aHR: 21.32, 95% CI 5.35-84.96; p<0.001) than those who had. there was no statistically significant difference in survival between patients suffering from colorectal and gastric cancers, and the grade of lymphocyte infiltration. Survival was significantly impacted by the presence of metastasis and the absence of treatment.

Impacts of the Coronavirus 2019 Pandemic on Gastrointestinal Endoscopy Volume and Diagnosis of Gastric and Colorectal Cancers: A Population-Based Study

IL-6 gene polymorphisms can play a role in the development or control of cancer by affecting cytokines. Gastrointestinal cancer is one of the most common types of cancer worldwide. The aim of this study was to investigate the effect of polymorphism of the IL-6 174G > C gene on gastrointestinal cancers based on a systematic review and meta-analysis, including gastric, colorectal, and esophageal cancer. In this study, a systematic and meta-analytical review of the study data on the effect of polymorphism of IL-6 174G > C gene on gastrointestinal cancer (gastric, colorectal, and esophageal cancer) in Scopus, EMBASE, Web of Science, PubMed, and Science Direct Databases was extracted without any time limit until April 2020. In order to perform the analysis of eligible studies, the model of random effects was used and the heterogeneity of studies was investigated with I2 index. Data analysis was performed with Comprehensive Meta-Analysis software (Version 2). The total number of surveyed studies in patients with colorectal cancer was 22 studies. Based on the results of meta-analysis, the odds ratio of GG genotype in patients with colorectal cancer was 0.88. The odds ratio of GC genotype obtained in patients with colorectal cancer was 0.88 and the odds ratio of CC genotype in patients with colorectal cancer was 0.92. The total number of surveyed studies in patients with gastric cancer was 12. Based on the meta-analysis results, the odds ratio of GG genotype in patients with gastric cancer was 0.74, the odds ratio of GC genotype in patients with gastric cancer was 1.27, and the odds ratio of CC genotype in patients with gastric cancer was 0.78. The total number of surveyed studies in esophageal cancer patients was 3 studies. Based on the results of meta-analysis, the odds ratio of GG genotype in patients with esophageal cancer was 0.57, the odds ratio of GC genotype in patients with esophageal cancer was 0.44, and the odds ratio of chance of CC genotype in patients with esophageal cancer was 0.99. In general, different genotypes of polymorphism of the IL-6 174G > C gene reduce the risk of gastric, colorectal, and esophageal cancer. However, the GC genotype of this gene was associated with a 27% increased risk of gastric cancer.