scholarly journals The Clinicopathological Significance of miR-133a in Colorectal Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Timothy Ming-Hun Wan ◽  
Colin Siu-Chi Lam ◽  
Lui Ng ◽  
Ariel Ka-Man Chow ◽  
Sunny Kit-Man Wong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Negative Correlation ◽  
Target Genes ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Tnm Staging ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Endogenous Expression ◽  
Clinicopathological Significance

This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient’s clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson’s method. MiR-133a was downregulated in 83.2% of tumors compared to normal mucosal tissue. Higher miR-133a expression in tumor tissues was associated with development of distant metastasis, advanced Dukes and TNM staging, and poor survival. The unfavorable prognosis of higher miR-133a expression was accompanied by dysregulation of potential miR-133a target genes, LIM and SH3 domain protein 1 (LASP1), Caveolin-1 (CAV1), and Fascin-1 (FSCN1). LASP1 was found to possess a negative correlation (γ=-), whereas CAV1 exhibited a significant positive correlation (γ=), and a stronger correlation was found in patients who developed distant metastases (γ=). In addition, a negative correlation of FSCN1 was only found in nonmetastatic patients. In conclusion, miR-133a was downregulated in CRC tissues, but its higher expression correlated with adverse clinical characteristics and poor prognosis.

scholarly journals Tumour Microbiome-Based Subtypes of Colorectal Cancer Correlate with Clinical Variables

2020 ◽  
Author(s):  
Barbora Zwinsová ◽  
Vyacheslav Petrov ◽  
Martina Hrivňáková ◽  
Stanislav Smatana ◽  
Lenka Micenková ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Primary Tumour ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Tnm Staging ◽  
Response To Treatment ◽  
Clinical Variable ◽  
Rrna Gene ◽  
Clinical Variables

Abstract BackgroundLong-term dysbiosis of the gut microbiome has a significant impact on the development, progression and the aggressiveness of colorectal cancer (CRC) and may explain part of the observed heterogeneity of the disease from phenotypic, prognostic and response to treatment perspectives. Although the shifts in gut microbiome in the normal-adenoma-carcinoma sequence have been described, the landscape of microbiome within CRC and its associations with clinical variables remain under-explored. ResultsWe performed 16S rRNA gene sequencing of paired tumour tissue, adjacent visually-normal mucosa and stool swabs of N=186 patients with stage 0-IV CRC to describe the tumour microbiome and its association with clinical variable and to derive tumour microbial subtypes.We identified new genera never previously associated with CRC tumour mucosa (Flavonifractor, Haemophilus, Howardella, Pseudomonas, Sutterella, Treponema 2) or CRC (Actinobacillus, Aggregatibacter, Bergeyella, Phocaeiola, Defluviitaleaceae UCG-011, Massilia, Tyzzerella 4). The bacteria residing on tumour-mucosa were dominated by genera belonging to (potential) oral pathogens. Based on tumour microbial profiles, we stratified CRC patients into three subtypes. The subtypes were significantly associated with prognostic factors such as tumor grade, primary tumour sidedness and TNM staging, with one subtype enriched in tumours with poor prognosis. Further, we inspected the associations of microbiome with clinical variables in a subtype-agnostic setting. The primary tumour-associated clinical variables predominantly correlated with tumour mucosal microbiome, while the presence of local and distant metastases was mostly associated with the stool microbiome.ConclusionsUnderstanding the interactions of the bacteria residing on tumour mucosa within different CRC tumour microbiome subtypes will help to better understand the underlying biological background of the heterogeneity of this disease. Indeed, the tumour microbiome is a possible source of additional integrative markers of CRC patients’ survival and prognosis. We found that CRC microbiome is strongly correlated with clinical variables, but these associations are dependent on the microbial environment (tumour mucosa, normal mucosa, stool). Our study thus identifies limitations of the usage of microbiome composition as marker of CRC progression, suggesting the need of combining several sampling sites (e.g. stool and tumour swabs).

scholarly journals Association between colorectal cancer and Fusobacterium nucleatum and Bacteroides fragilis bacteria in Iranian patients: a preliminary study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Relative Abundance ◽  
Normal Tissue ◽  
Bacteroides Fragilis ◽  
Fusobacterium Nucleatum ◽  
Normal Mucosa ◽  
Clinicopathologic Characteristics ◽  
Tissue Samples ◽  
Adjacent Normal Mucosa ◽  
Iranian Patients

Abstract Background and aim Recent studies have proposed that commensal bacteria might be involved in the development and progression of gastrointestinal disorders such as colorectal cancer (CRC). Therefore, in this study, the relative abundance of Fusobacterium nucleatum, Bacteroides fragilis, Streptococcus bovis/gallolyticus, and Enteropathogenic Escherichia coli (EPEC) in CRC tissues, and their association with clinicopathologic characteristics of CRC was investigated in Iranian patients. Moreover, the role of these bacteria in the CRC-associated mutations including PIK3CA, KRAS, and BRAF was studied. Method To these ends, the noted bacteria were quantified in paired tumors and normal tissue specimens of 30 CRC patients, by TaqMan quantitative Real-Time Polymerase Chain Reaction (qPCR). Next, possible correlations between clinicopathologic factors and mutations in PIK3CA, KRAS, and BRAF genes were analyzed. Results In studied samples, B. fragilis was the most abundant bacteria that was detected in 66 and 60% of paired tumor and normal samples, respectively. Furthermore, 15% of the B. fragilis-positive patients were infected with Enterotoxigenic B. fragilis (ETBF) in both adenocarcinoma and matched adjacent normal samples. F. nucleatum was also identified in 23% of tumors and 13% of adjacent normal tissue samples. Moreover, the relative abundance of these bacteria determined by 2-ΔCT was significantly higher in CRC samples than in adjacent normal mucosa (p < 0.05). On the other hand, our findings indicated that S. gallolyticus and EPEC, compared to adjacent normal mucosa, were not prevalent in CRC tissues. Finally, our results revealed a correlation between F. nucleatum-positive patients and the KRAS mutation (p = 0.02), while analyses did not show any association between bacteria and mutation in PIK3CA and BRAF genes. Conclusion The present study is the first report on the analysis of different bacteria in CRC tissue samples of Iranian patients. Our findings revealed that F. nucleatum and B. fragilis might be linked to CRC. However, any link between gut microbiome dysbiosis and CRC remains unknown.

scholarly journals LncRNA SNHG6 promotes chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in colorectal cancer cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xinke Wang ◽  
Zhixian Lan ◽  
Juan He ◽  
Qiuhua Lai ◽  
Xiang Yao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Western Blotting ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Chemotherapy Resistance ◽  
Micro Rna ◽  
Luciferase Reporter ◽  
Qrt Pcr ◽  
Reporter Assays

Abstract Background Chemotherapy resistance is one of the main causes of recurrence in colorectal cancer (CRC) patients and leads to poor prognosis. Long noncoding RNAs (lncRNAs) have been reported to regulate chemoresistance. We aimed to determine the role of the lncRNA small nucleolar RNA host gene 6 (SNHG6) in CRC cell chemoresistance. Methods Cell drug sensitivity tests and flow cytometry were performed to analyze CRC cell chemoresistance. Animal models were used to determine chemoresistance in vivo, and micro RNA (miRNA) binding sites were detected by dual-luciferase reporter assays. Bioinformatics analysis was performed to predict miRNAs binding to SNHG6 and target genes of miR-26a-5p. SNHG6/miR-26a-5p/ULK1 axis and autophagy-related proteins were detected by qRT-PCR and western blotting. Furthermore, immunofluorescence was employed to confirm the presence of autophagosomes. Results SNHG6 enhanced CRC cell resistance to 5-fluorouracil (5-FU), promoted autophagy, inhibited 5-FU-induced apoptosis, and increased 5-FU resistance in vivo. Bioinformatics analysis showed that miR-26a-5p might bind to SNHG6 and target ULK1, and dual-luciferase reporter assays confirmed this activity. qRT-PCR and western blotting showed that SNHG6 was able to negatively regulate miR-26a-5p but correlated positively with ULK1. Conclusion SNHG6 may promote chemoresistance through ULK1-induced autophagy by sponging miR-26a-5p in CRC cells.

scholarly journals Colon cancer surgery in patients operated on an emergency basis

2017 ◽  
Vol 44 (5) ◽  
pp. 465-470
Author(s):  
Rodrigo Felippe Ramos ◽  
Lucas Carvalho Santos dos-Reis ◽  
Beatriz Esteves Borgeth Teixeira ◽  
Igor Maroso Andrade ◽  
Jaqueline Suelen Sulzbach ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Disease Recurrence ◽  
Tumor Location ◽  
Tnm Staging ◽  
Curative Intent ◽  
Initial Stage ◽  
Epidemiological Profile ◽  
Colorectal Cancer Patients

ABSTRACT Objective: to study the epidemiological profile of patients with colorectal cancer operated on an emergency basis at the Bonsucesso Federal Hospital. Methods: this is a retrospective study of patients operated between January 1999 and December 2012. We analyzed the following variables: age, gender, clinical data, TMN staging, tumor location, survival and types of surgery. Results: we evaluated 130 patients in the study period. The most frequent clinical picture was intestinal obstruction, in 78% of cases. Intestinal perforation was the surgical indication in 15%. The majority (39%) of the patients had advanced TNM staging, compared with 27% in the initial stage. There were 39 deaths (30%) documented in the period. The most common tumor site was the sigmoid colon (51%), followed by the ascending colon (16%). The curative intent was performed in most cases, with adjuvant treatment being performed in 40% of the patients. Distant metastases were found in 42% of the patients and 10% had documented disease recurrence. Disease-free survival at two and five years was 69% and 41%, respectively. Conclusion: there was a high mortality rate and a low survival rate in colorectal cancer patients operated on urgently.

scholarly journals Expressions of TWIST1 and CD105 markers in colorectal cancer patients and their association with metastatic potential and prognosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Fahimeh Fattahi ◽  
Leili Saeednejad Zanjani ◽  
Somayeh Vafaei ◽  
Zohreh Habibi Shams ◽  
Jafar Kiani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endothelial Cells ◽  
Epithelial Cells ◽  
Tumor Cells ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
Clinicopathological Parameters ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Nuclear Expression

Abstract Background TWIST1 and CD105, which contribute to tumor malignancy, are overexpressed in cancers. Accordingly, TWIST1 enhances epithelial-to-mesenchymal transition (EMT) and promotes the formation of cancer stem cells (CSCs). Also, CD105 is a neoangiogenesis marker in endothelial cells, which is introduced as a CSC marker in tumoral epithelial cells in several types of cancers. The present study was aimed to investigate expressions of TWIST1 and CD105 in colorectal cancer (CRC) patients. Methods Expressions of TWIST1 and CD105 in 250 CRC tissue samples were evaluated using immunohistochemistry on tissue microarrays (TMAs). In this regard, TWIST1 expression was investigated in the subcellular locations (cytoplasm and nucleus), while CD105 was mapped in endothelial cells and cytoplasmic tumor cells of CRC tissues. The association between the expression of these markers and clinicopathological parameters, as well as survival outcomes were analyzed. Results Results indicate a statistically significant association between higher nuclear expression levels of TWIST1 and distant metastases in CRC (P = 0.040) patients. In addition, it was shown that the increased nuclear expression of TWIST1 had a poor prognostic value for disease-specific survival (DSS) and progression-free survival (PFS) (P = 0.042, P = 0.043, respectively) in patients with CRC. Moreover, analysis of CD105 expression level has revealed that there is a statistically significant association between the increased expression of CD105 in tumoral epithelial cells and more advanced TNM stage (P = 0.050). Conclusions Our results demonstrate that nuclear TWIST1 and cytoplasmic CD105 expressions in tumor cells had associations with more aggressive tumor behavior and more advanced diseases in CRC cases.

scholarly journals Identifying Differentially Expressed tRNA-Derived Small Fragments as a Biomarker for the Progression and Metastasis of Colorectal Cancer

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
Hui Chen ◽  
Zhiying Xu ◽  
Hua Cai ◽  
Ya Peng ◽  
Li Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Confidence Interval ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Clinical Stage ◽  
Cancer Cell Line ◽  
Differentially Expressed ◽  
Colorectal Cancer Cell Line ◽  
Mesenchymal Transition ◽  
Qrt Pcr

Objectives. The epithelial-to-mesenchymal transition (EMT) is one key step for the invasion and metastasis of colorectal cancer (CRC). Up until now, the underlying mechanism of EMT in CRC is still unpromising. Thus, it is essential to have a better understanding of its carcinogenesis. The transfer RNA-derived small fragments (tsRNAs) are a new group of small noncoding RNAs (sncRNAs), including tRNA-derived stress-induced RNAs (tiRNAs) and tRNA-derived fragments (tRFs), which have been observed to play an important role in many cancers. However, the relationship between tRFs and EMT in CRC is still unknown. Herein, we aimed to investigate the involvement of tRFs in EMT and its contribution to CRC development. Methods. We identified the differentially expressed tsRNAs in colorectal cancer cell line HT29 treated with TGF-β compared with control cells by using high-throughput sequencing and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). QRT-PCR was conducted to validate the differentially expressed fragments in 68 CRC tumor samples (22 women and 46 men) and adjacent nontumor samples. The association of the expression of tRFs with CRC metastasis and clinical stage was analyzed. Meanwhile, the correlation between tRF expression and overall survival (OS) was also analyzed. TargetScan and miRanda and multiple bioinformatic approaches were used to predict the possible target genes of tsRNAs and analyze possible functions of the tRFs. Results. A series of differentially expressed tsRNAs were identified in TGF-β-treated HT29 cells compared with control cells. tRF-phe-GAA-031 and tRF-VAL-TCA-002 were found to be significantly upregulated in CRC tissues compared to adjacent nontumor tissues. They were significantly correlated with distant metastasis and clinical stage. We compared the differences between tumor samples and nontumor tissues from the ROC curves. The area under the ROC curve (AUC) was up to 0.7554 (95% confidence interval: 0.6739 to 0.8369, p < 0.0001 ) for tRF-Phe-GAA-031 and up to 0.7313 (95% confidence interval: 0.6474 to 0.8151, p < 0.0001 ) for tRF-VAL-TCA-002. For OS analysis, higher tRF-phe-GAA-031 and tRF-VAL-TCA-002 expressions were associated with shorter survival for CRC patients. Conclusion. A series of differentially expressed tsRNAs are identified in the EMT process of CRC. And tRF-phe-GAA-031 and tRF-VAL-TCA-002 are higher expressed in CRC tissues, and they might play an important role in the metastasis of CRC. Meanwhile, they may be potential biomarkers and intervention targets in the clinical treatment of CRC.

scholarly journals The levels of sICAM-1, sELAM-1, TNFα and sTNFR1 proteins in patients with colorectal adenocarcinoma in tumor and corresponding normal mucosa

2020 ◽  
Author(s):  
Joanna K. Strzelczyk ◽  
Piotr Cuber ◽  
Benjamin Bochon ◽  
Krzysztof Gajdzik ◽  
Janusz Strzelczyk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Colorectal Adenocarcinoma ◽  
Cancer Survival ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Protein Levels ◽  
Tissue Homogenates ◽  
Clinical Profiles ◽  
Tissue Specimens

Colorectal cancer is a common malign disease of the gastrointestinal tract. The cancer survival rate depends on the stage of the disease at detection time. It is well known that several molecular mechanisms are involved in cancer and some molecules might affect or modulate neogenesis. The aim of the study was to assess the levels of sICAM-1, sELAM-1, TNFα and sTNFR1 protein in tumor and corresponding normal mucosa in a group of patients with colorectal adenocarcinoma and also associations of these parameters with demographic and clinical profiles of the patients. Tissue specimens were obtained during resection of neoplastic lesions. Protein levels were assayed in tissue homogenates by ELISA. The protein level of sICAM-1 in tumor was significantly increased in comparison to the corresponding normal mucosa (80.06 ng/mg vs 69.53 ng/mg, p=0.02). Furthermore, a significant positive correlation between sICAM-1 and sTNFR1 proteins levels in tumor (rs=0.58, p<0.001) and in corresponding normal mucosa (rs=0.48, p<0.001) was found. Also, significant correlations in corresponding normal mucosa were found between sELAM-1 and sICAM-1 (rs=0.58, p<0.001) and between sTNFR1 and sELAM-1 (rs=0.57, p<0.001). Significantly higher level of sTNFR1 in corresponding normal mucosa samples of patients with distant metastases was observed (p=0.04). Obtained results suggest that sICAM-1 protein could be considered as colorectal cancer marker. Furthermore, sTNFR1 also has the potential to become a good prognostic marker used during monitoring of the patients. Nevertheless, a further study in this area to confirm this correlation is required.

scholarly journals Regulation Network of Colorectal-Cancer-Specific Enhancers in the Progression of Colorectal Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8337
Author(s):  
Bohan Chen ◽  
Yiping Ma ◽  
Jinfang Bi ◽  
Wenbin Wang ◽  
Anshun He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Target Genes ◽  
Colorectal Cancer Cell Line ◽  
Tissue Samples ◽  
Colon Cells ◽  
Colorectal Cancer Cells ◽  
Regulation Network

Enhancers regulate multiple genes via higher-order chromatin structures, and they further affect cancer progression. Epigenetic changes in cancer cells activate several cancer-specific enhancers that are silenced in normal cells. These cancer-specific enhancers are potential therapeutic targets of cancer. However, the functions and regulation networks of colorectal-cancer-specific enhancers are still unknown. In this study, we profile colorectal-cancer-specific enhancers and reveal their regulation network through the analysis of HiChIP data that were derived from a colorectal cancer cell line and Hi-C and RNA-seq data that were derived from tissue samples by in silico analysis and in vitro experiments. Enhancer–promoter loops in colorectal cancer cells containing colorectal-cancer-specific enhancers are involved in more than 50% of the topological associated domains (TADs) changed in colorectal cancer cells compared to normal colon cells. In addition, colorectal-cancer-specific enhancers interact with 152 genes that are significantly and highly expressed in colorectal cancer cells. These colorectal-cancer-specific enhancer target genes include ITGB4, RECQL4, MSLN, and GDF15. We propose that the regulation network of colorectal-cancer-specific enhancers plays an important role in the progression of colorectal cancer.

Selection of reference genes for quantitative real-time PCR normalization in the coffee white stem borer, Xylotrechus quadripes Chevrolat (Coleoptera: Cerambycidae)

2021 ◽  
pp. 1-11
Author(s):  
Qianqian Meng ◽  
Benshui Shu ◽  
Shiwei Sun ◽  
Ying Wang ◽  
Mei Yang ◽  
...  
Keyword(s):  
Real Time ◽  
Reference Genes ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Stem Borer ◽  
Internal Reference ◽  
Experimental Conditions ◽  
Tissue Samples ◽  
Abiotic Conditions ◽  
Qrt Pcr

Abstract The coffee white stem borer, Xylotrechus quadripes Chevrolat (Coleoptera: Cerambycidae), is a major destructive pest of Coffea arabica L. (Gentianales: Rubiaceae), widely planted in many Asian countries, including China. Quantitative real-time polymerase chain reaction (qRT-PCR) is a common method for quantitative analysis of gene transcription levels. To obtain accurate and reliable qRT-PCR results, it is necessary to select suitable reference genes to different experimental conditions for normalizing the target gene expression. However, the stability of the expression of reference genes in X. quadripes has rarely been studied. In this study, the expression stability of nine candidate reference genes were investigated under biotic and abiotic conditions for use in qRT-PCR's normalization. By integrating the results of four algorithms of NormFinder, BestKeeper, geNorm, and RefFinder, the optimal reference gene combinations in different experimental conditions were performed as follows: RPL10a and EIF3D were the optimal reference genes for developmental stage samples, EIF4E, RPL10a, and RPS27a for tissue samples, V-ATP and EF1α for the sex samples, EIF3D and V-ATP for temperature treatment, RPS27a and RPL10a for insecticide stress, and RPL10a, RPS27a, and EF1α for all the samples. This study will help to obtain the stable internal reference genes under biotic and abiotic conditions and lay the foundation for in-depth functional research of target genes or genomics on olfactory molecular mechanisms, temperature adaptability, and insecticide resistance in X. quadripes.

Activity of Matrix Metalloproteinases-2 and -9 in Advanced Laryngeal Cancer

2003 ◽  
Vol 128 (1) ◽  
pp. 132-136 ◽  
Author(s):  
Michal Bogusiewicz ◽  
Marta Stryjecka-Zimmer ◽  
Marcin Szymanski ◽  
Tomasz Rechberger ◽  
Wieslaw Golabek
Keyword(s):  
Matrix Metalloproteinases ◽  
Laryngeal Cancer ◽  
Malignant Tumors ◽  
Proteolytic Enzymes ◽  
Distant Metastases ◽  
Normal Mucosa ◽  
Collagen Type Iv ◽  
Primary Therapy ◽  
Tissue Samples ◽  
Type Iv

OBJECTIVES: Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) are proteolytic enzymes that digest collagen type IV and other components of the basement membrane. They play a key role in local invasion and the formation of distant metastases by malignant tumors. The aim of this study was to evaluate the activity of MMP-2 and MMP-9 in stage III and IV laryngeal cancers. STUDY DESIGN: In the study we used specimens of laryngeal cancer and surrounding normal mucosa obtained from 23 patients undergoing surgical treatment as a primary therapy. After extraction of MMP-2 and MMP-9 from tissue samples, their activity was assessed with zymography. RESULTS: Greater activity of MMP-2 and MMP-9 and a higher active/latent MMP-2 ratio were found in cancer compared with normal mucosa. Moreover, N2 tumors revealed greater activity of MMP-2 in comparison with N1 and N0 tumors. CONCLUSIONS: Results of the study indicate that both MMP-2 and MMP-9 may be involved in the expansion of laryngeal cancer. MMP-2 may also play an important role in the lymphatic spread of some laryngeal tumors.

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