scholarly journals Expression of Extracellular Matrix-Related Genes and Their Regulatory microRNAs in Problematic Colorectal Polyps

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3715
Author(s):  
Margareta Žlajpah ◽  
Emanuela Boštjančič ◽  
Bojan Tepeš ◽  
Nina Zidar

Colorectal carcinoma usually evolves gradually, forming a spectrum of lesions, due to accumulation of genetic mutations and epigenetic alterations. Many early lesions are detected since the introduction of screening programs. The greatest challenge is to distinguish between adenomas with epithelial misplacement (AEM) and adenomas with early carcinoma (AEC), considering the diagnosis affects prognosis and treatment. We analyzed the expression of selected extracellular matrix (ECM)-related genes and proteins, and their regulatory microRNAs using RT-qPCR and immunohistochemistry in biopsies from 44 patients. Differences were observed in AEM in comparison to AEC for DCN, EPHA4, FN1, SPON2, and SPP1, reflecting inflammatory stromal reaction to traumatisation and misplacement of dysplastic glands in the submucosa in the former, and desmoplastic stromal reaction to true invasion of dysplastic glands in the submucosa in the latter. Expression of regulatory microRNAs hsa-miR-200c and hsa-miR-146a significantly negatively correlated with the expression of their regulated genes, while significant difference between AEM and AEC was observed only for hsa-miR-29c. The described expression patterns are too complex to be used in diagnostic work, but might contribute to better understanding ECM changes in colorectal carcinoma development, helping to find new markers in the future.

2019 ◽  
Vol 122 (4) ◽  
pp. 590-594
Author(s):  
Irma van de Beek ◽  
Iris E. Glykofridis ◽  
Rob M. F. Wolthuis ◽  
Hans J. J. P. Gille ◽  
Paul C. Johannesma ◽  
...  

Abstract Background Previously, it has been suggested that colorectal polyps and carcinomas might be associated with Birt-Hogg-Dubé syndrome. We aimed to compare the occurrence of colorectal neoplasms between Dutch patients with Birt-Hogg-Dubé syndrome and their relatives without Birt-Hogg-Dubé syndrome. Methods In all, 399 patients with a pathogenic FLCN mutation and 382 relatives without the familial FLCN mutation were included. Anonymous data on colon and rectum pathology was provided by PALGA: the Dutch Pathology Registry. Results No significant difference in the percentage of individuals with a history of colorectal carcinoma was found between the two groups (3.6% vs 2.6%, p = 0.54). There was also no significant difference between the age at diagnosis, diameter, differentiation and location of the colorectal carcinomas. Significantly more individuals with Birt-Hogg-Dubé syndrome underwent removal of colorectal polyps (12.2% vs 6.3%, p = 0.005). However, there was no significant difference between the number of polyps per person, the histology, grade of dysplasia and location of the polyps. Conclusion Our data do not provide evidence for an increased risk for colorectal carcinoma in Birt-Hogg-Dubé syndrome, arguing against the need for colorectal surveillance. The difference in polyps might be due to a bias caused by a higher number of colonoscopies in patients with Birt-Hogg-Dubé syndrome.


2021 ◽  
Vol 09 (01) ◽  
pp. E9-E13
Author(s):  
Sachin Srinivasan ◽  
Peter D. Siersema ◽  
Madhav Desai

Abstract Background and study aims Diminutive colorectal polyps are increasingly being detected and it is not clear whether jumbo biopsy forceps (JBF) has comparable efficacy to that of cold snare polypectomy (CSP) for management of these lesions. Methods An electronic literature search was performed for studies comparing resection rates of JBF and CSP for diminutive polyps (≤ 5 mm). The primary outcome was incomplete resection rate (IRR). Secondary outcomes included failure of tissue retrieval and complication rates (post-polypectomy bleeding, perforation etc.). Leave-one-out analysis was performed to examine the disproportionate role of any of the studies. Meta-analysis outcomes and heterogeneity (I2) were computed using Comprehensive meta-analysis software. Results A total of 4 studies (3 randomized controlled trials and 1 retrospective study) with 407 patients and 569 total polyps (mean size of 3.62 mm) was included for analysis. IRR of JBF was slightly higher than that of CSP (10.2 % vs 7.2 %) but this was not statistically significantly different (Pooled OR 1.76; 95 % CI 0.94–3.28; I2 = 0). Leave-one-out analysis showed no significant difference in the pooled OR comparison either. Two of the 4 studies reported 0 % failure of tissue retrieval for JBF and 1 % and 4.3 % for CSP. There were no complications for either group from the 2 studies that reported this outcome. The quality of the included studies was moderate to high. Conclusions This systematic review with only limited data shows that JBF and CSP are not statistically different in completely removing diminutive polyps, although careful endoscopic assessment is needed to ensure complete removal of all polyp tissue.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shihao Zhao ◽  
Feng Wang ◽  
Qiuping Zhang ◽  
Jiayi Zou ◽  
Zhangshu Xie ◽  
...  

AbstractMost of the cotton bollworm-resistant genes applied in cotton are more than 20 years and they all belong to Cry1Ab/c family, but the insect-resistant effects of Cry5Aa on cotton were rarely reported. The possible risk of resistance is increasing. The study synthesized a novel bollworm-resistant gene Cry5Aa artificially based on preferences of cotton codon. The new gene was transferred to cotton through the method of pollen tube pathway. The transgenic strains were identified by kanamycin test in field and laboratory PCR analysis. Meanwhile, an insect resistance test was conducted by artificial bollworm feeding with transgenic leaves and GK19 was used as a control in this study. Results showed that rate of positive transgenic strains with kanamycin resistance in the first generation (T1), the second generation (T2) and the third generation (T3) respectively were 7.76%, 73.1% and 95.5%. However, PCR analysis showed that the positive strain rate in T1, T2 and T3 were 2.35%, 55.8% and 94.5%, respectively. The resistant assay of cotton bollworm showed that the mortality rate of the second, third and fourth instar larva feed by the transgenic cotton leaves, were 85.42%, 73.35% and 62.79%, respectively. There was a significant difference between transgenic plant of Cry5Aa and GK19 in insect resistance. Finally, we also conducted the further analysis of gene expression patterns, gene flow and the effect on non-target pest in the study. The results showed that Cry5Aa gene had less environmental impact, and Cry5Aa has been transferred successfully and expressed stably in cotton. Therefore, the novel bollworm resistance gene can partially replace the current insect-resistance gene of Lepidoptera insects.


2016 ◽  
Vol 11 (1) ◽  
pp. 287-292
Author(s):  
Xiao-yang Liu ◽  
Hua Liu ◽  
Lin Gu ◽  
Hai-lun Zheng

AbstractObjectiveTo explore the correlation between the enhancer of zeste homolog 2 (EZH2) expression and clinicopathological features in colorectal cancer patients.MethodsA total of sixty-six patients with colorectal carcinoma were admitted to our general surgery department from January 2011 to December 2014. The EZH2 expression levels in the cancer tissues (CTs) from the 66 patients with colorectal cancer and those in distant normal colorectal tissues from 30 cases were examined through immunohistochemistry and western blotting assays. The relationship between the expression of EZH2 and the clinicopathological features and prognosis of the patients was analyzed.ResultsEZH2 in colorectal carcinoma tissues is granularly brown, predominantly expressed and diffused in the nuclei of tumor cells. Positive rates of EZH2 in intestinal CTs and in distant normal intestinal tissues are 62.12% (41/66) and 6.67% (2/30), respectively with significant difference (P < 0.05). Western blotting also confirmed its elevated expression in colorectal CTs. EZH2-positive expression in CTs was related to degree of differentiation, Duke staging, and tumor size (P < 0.05) but was unrelated to the patient’s gender, age or tumor site (P = 0.05). The 3-year progression-free survival (PFS) rates of the EZH2-positive group and the EZH2-negative group were 43.8% and 67.5%, respectively. The risk of disease progression of the EZH2-positive patients in the follow-up period was significantly higher than that of the EZH2-negative patients (HR = 2.49, 95% CI = 1.04–4.80, P < 0.05).ConclusionEZH2 is closely related to colorectal carcinoma development and disease progression, and thus could be used as a tumor biomarker that may indicate prognosis.


2021 ◽  
Author(s):  
Zhuo Liu ◽  
Feng He ◽  
Jing Liu ◽  
Shengrong OuYang ◽  
Zexi Li ◽  
...  

Abstract Background Wilms’ tumor, also called nephroblastoma, is the most common pediatric renal malignancy. The pathogenesis of Wilms’ tumor has been attributed to several genetic and epigenetic factors. However, the most pervasive internal mRNA modification that affects almost every process of RNA metabolism, RNA N6-Methyladenosine (m6A) methylation, has not been characterized in Wilms’ tumor. Methods Wilms’ tumor (WT) and adjacent non-cancerous (NC) tissue samples were obtained from 23 children with nephroblastoma, and the global m6A levels were measured by mass spectrometry. Analyses by m6A-mRNA epitranscriptomic microarray and mRNA microarray were performed, and m6A-related mRNAs were validated by quantitative real-time PCR for input and m6A-immunoprecipitated RNA samples from WT and NC tissues. Gene ontology analysis and KEGG pathway analysis were performed for differentially expressed genes, and expression of RNA methylation-related factors was measured by quantitative real-time PCR. Results The total m6A methylation levels in total RNA of WT samples and NC samples were (0.21 ± 0.01)% and (0.22 ± 0.01)%, respectively, with no statistically significant difference. Fifty-nine transcripts were differentially m6A-methylated between the WT and NC groups, which showed distinct m6A modification patterns. Gene ontology analysis indicated that m6A-modified genes were enriched in cancer-associated pathways, including the mTOR pathway, and conjoint analysis of the unique methylation and gene expression patterns in WT samples suggested an association with metabolic pathways.The mRNA levels of the m6A-related “reader” genes, YTHDF1, YTHDF2 and IGF2BP3, were statistically higher in WT samples than in NC samples. Conclusion This is the first study to determine the m6A modification profiles in Wilms’ tumor. Our data provide novel information regarding patterns of m6A modification that correlate with carcinogenesis in Wilms’ tumor.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Amany H. Abdelrahman ◽  
Ola M. Eid ◽  
Mona H. Ibrahim ◽  
Safa N. Abd El-Fattah ◽  
Maha M. Eid ◽  
...  

Abstract Background Autism spectrum disorder is a condition related to brain development that affects a person’s perception and socialization, resulting in problems in social interaction and communication. It has no single known cause, yet several different genes appear to be involved in autism. As a genetically complex disease, dysregulation of miRNA expression and miRNA–mRNA interactions might be a feature of autism spectrum disorder. The aim of the current study was to investigate the expression profile of circulating miRNA-128, miRNA-7 and SHANK gene family in ASD patients and to assess the possible influence of miRNA-128 and miRNA-7 on SHANK genes, which might provide an insight into the pathogenic mechanisms of ASD and introduce noninvasive molecular biomarkers for the disease diagnosis and prognosis. Quantitative real-time PCR technique was employed to determine expression levels of miRNA-128, miRNA-7 and SHANK gene family in blood samples of 40 autistic cases along with 30 age- and sex-matched normal volunteer subjects. Results Our study revealed a statistical significant upregulation of miRNA-128 expression levels in ASD cases compared to controls (p value < 0.001). A statistical significant difference in SHANK-3 expression was encountered on comparing cases to controls (p value < 0.001). However, miRNA-7 expression showed no significant difference between the studied groups. Conclusions MiRNA-128 and SHANK-3 gene are emerging players in the field of ASD. They are promising candidates as noninvasive biomarkers in autism. Future studies are needed to emphasize their pivotal role.


2021 ◽  
Vol 5 (1) ◽  
pp. 28-33
Author(s):  
Merza H. Homady ◽  
Tanya S. Salih ◽  
Mariamm M. Al-Jubori ◽  
Mustafa D. Younus

The study inc1uded 50 tissue blocks embedded in paraffin wax (16 females and 34 males), obtained from a patients group with (CRC) colorectal cancer , as well as 35 Tissue blocks that were embedded in paraffin wax from norma1 co1on (ulcerative co1itis) as controls. A relatively few oncogenes and most prominently tumor-suppressing genes, Kirastien rat sarcoma virus (KRAS), and P53 genes have been mutated into a significant part of CRCs, and a broad collection of mutated genes has been defined in CRC subsets. Current findings showed very significant differences between patients and control subjects in the p53 positive rate (P<0.001). TP53 Pro/Pro genotype positivity was higher in the contro1 group I than in the patient group I and this was a significant difference (Pi<0.001) with an odd ratio of less than one. The genotype Pro/Pro was considered to be protective against colorectal carcinoma preventively fractured 0.767. The positive rate of p53 Arg/Arg genotype in patients was more frequent and statistically significant (P <0.01), because the odd ratio was more than one. The genotype Arg/Arg would be considered a colorectal carcinoma risk factor. We conclude that p53 over expression is used as an indicator of p53 mutation (as identified by immuno-historic chemistry) and KRAS protein expression was negatively impaired for all the patients in the current study.


Author(s):  
Bianca Astrogildo de FREITAS ◽  
Carlos Alberto Tomatis LOTH ◽  
Gustavo Lazaroto SWAROWSKY ◽  
Graziela Morais LOURENÇO ◽  
Lucio Sarubbi FILLMANN ◽  
...  

ABSTRACT Background: One of the most important concerns on health is the increased rates of obesity in population and the speed in which this number is increasing. This number translates a serious public health problem, since it also increases the risk of several other diseases associated with obesity resulting in significant morbidity and mortality. Among them, it seems to be connected to several neoplasms, such as colorectal carcinoma. Aim: To evaluate the impact of obesity as a risk factor for colorectal carcinoma through the detection of adenoma, and to discuss the mechanisms that could establish a link between obesity and neoplasm. Methods: Patients who underwent colonoscopy were included. Personal and anthropometric data, clinical history, and results of the tests were analyzed in order to verify the correlation of BMI and the presence of adenomatous polyps. Results: A total of 142 patients were studied, which a mean age of 62 years. Of the patients, 74 (52.1%) were men and 68 (47.9%) were. Obesity was identified in 16.2% of the patients. Polyps were found in 61 (42.9%), mostly smaller than 1 cm. Obese individuals were 1.56 times more likely to present colorectal adenoma than patients with normal weight. Conclusion: This study, although showing the greater presence of colorectal adenomas in obese individuals, did not show a significant difference in the occurrence of pre-malignant lesions.


2021 ◽  
Author(s):  
Thérèse Rachell Theodoro ◽  
Rodrigo Lorenzetti Serrano ◽  
Karine Corcione Turke ◽  
Sarhan Sydney Saad ◽  
Marcelo Augusto Fontenelle Ribeiro Junior ◽  
...  

AbstractThe process of proliferation and invasion of tumor cells depends on changes in the extracellular matrix (ECM) through the activation of enzymes and alterations in the profile of ECM components. We aimed to investigate the mRNA and protein expression of ECM components such as heparanase (HPSE), heparanase-2 (HPSE2), matrix metalloproteinase-9 (MMP-9), and syndecan-1 (SYND1) in neoplastic and non-neoplastic tissues of patients with colorectal carcinoma (CRC). It is a cross-sectional study in which twenty-four adult patients that had CRC were submitted to resection surgery. We analyzed the expression of HPSE, HPSE2, MMP-9, and SYND1 by quantitative RT-PCR and immunohistochemistry. Differing from most of the studies that compare the mRNA expression between tumor samples and non-neoplastic tissues, we decided to investigate whether variations exist in the expression of the ECM components between the affected tissue and nontumoral tissue collected from the same patient with CRC. We removed both tissue samples immediately after the surgical resection of CRC. The data showed higher mRNA and protein expression of HPSE2 (P = 0.0058), MMP-9 (P = 0.0268), and SYND1 (P = 0.0002) in tumor samples compared to the non-neoplastic tissues, while there was only an increase in the level of HPSE protein in tumor tissues. A greater expression of HPSE2 was observed in patients with lymph node metastasis (P = 0.048), suggesting that such protein can be a marker of lymph node metastasis in CRC.


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