scholarly journals Expression Patterns of Xenobiotic-Metabolizing Enzymes in Tumor and Adjacent Normal Mucosa Tissues among Patients with Colorectal Cancer: The ColoCare Study

2019 ◽  
Vol 29 (2) ◽  
pp. 460-469 ◽  
Author(s):  
Jolantha Beyerle ◽  
Andreana N. Holowatyj ◽  
Mariam Haffa ◽  
Eva Frei ◽  
Biljana Gigic ◽  
...  
2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aref Shariati ◽  
Shabnam Razavi ◽  
Ehsanollah Ghaznavi-Rad ◽  
Behnaz Jahanbin ◽  
Abolfazl Akbari ◽  
...  

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.


2003 ◽  
Vol 51 (5) ◽  
pp. 567-573 ◽  
Author(s):  
Hide Kasai ◽  
Daita Nadano ◽  
Eiko Hidaka ◽  
Kayoko Higuchi ◽  
Masatomo Kawakubo ◽  
...  

Ribosomal proteins are a major component of ribosomes and play critical roles in protein biosynthesis. Recently it has been shown that the ribosomal proteins also function during various cellular processes that are independent of protein biosynthesis therefore called extraribosomal functions. In this study we have, for the first time, determined the expression profile of 12 ribosomal proteins (Sa, S8, S11, S12, S18, S24, L7, L13a, L18, L28, L32, and L35a) in normal epithelia of human colorectal mucosa using immunohistochemistry (IHC) and then compared their expression patterns with those of colorectal cancer. In the normal mucosa, ribosomal proteins were largely associated with the ribosomes of mucosal epithelia, and the expression level of ribosomal proteins, except for S11 and L7 proteins, was markedly increased in associated with maturation of the mucosal cells. On the other hand, these ribosomal proteins were markedly decreased in colorectal cancer compared with the normal mucosa. By contrast, S11 and L7 ribosomal proteins were rarely associated with the ribosomes of colorectal epithlia except immature mucosal cells, whereas their expression levels were significantly enchanced in colorectal cancer cells. In addition, L7 ribosomal protien was detected in the secretory granules of the enterochromaffin cells in the colorectal mucosa and in carcinoma cells expressing chromogranin A. These results indicate that the expression of ribosomal proteins is differentially regulated not only in normal mucosa but also in carcinoma of human colorectum, and suggest an extraribosomal function of L7 ribosomal protein in neuroendocrine function.


2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He

Abstract Abstract Background: Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the expression patterns as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 101 CRC specimens. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo . Conclusions: Our study demonstrates the aberrant expression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a novel prognostic biomarker for CRC patients, especially for CRC patients with distant metastasis.


2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He

Abstract Abstract Background: Angiogenic factor with G-patch and FHA domains 1 (AGGF1) can promote angiogenesis and increasing evidence has highlighted the important roles of AGGF1 in tumorigenesis. However, the expression patterns as well as the biological functions of AGGF1 in colorectal cancer (CRC) remain to be established. The purpose of the present study is therefore to identify the effect of AGGF1 on prognosis and metastasis in CRC patients. Methods: The expression level of AGGF1 in CRC was examined by qPCR, western blot and immunohistochemistry in a tissue microarray containing 101 CRC specimens. And the effect of AGGF1 on CRC cell malignance was investigated in our established stable AGGF1 upregulated and knockdown CRC cell lines. Results: The expression level of AGGF1 in CRC tissue was not significantly different to that in adjacent normal mucosa at the mRNA level. However, at the protein level, AGGF1 expression in CRC tissues was significantly higher than in paired normal mucosa, which showed a clear association with TNM stage, AJCC stage, vascular invasion, and differentiation. Further, we revealed an apparent correlation between AGGF1 expression and poorer disease-free survival and overall survival of CRC patients. In addition, we discovered that AGGF1 significantly promoted CRC cell wound healing, migration, and invasion in vitro and distant metastasis in vivo . Conclusions: Our study demonstrates the aberrant expression of AGGF1 in CRC and provides a basis on which to explore the application of AGGF1 as a novel prognostic biomarker for CRC patients, especially for CRC patients with distant metastasis.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15138-e15138
Author(s):  
Maria Del Pilar Solis Hernandez ◽  
Ivan Fernandez-Vega ◽  
Olivia García-Suárez ◽  
Natalia Perez Lopez ◽  
Luis M Quirós ◽  
...  

e15138 Background: Colorectal cancer (CRC) is a heterogeneous disease defined by anatomic, functional and molecular differences depending on the primary tumor location (PTL). Several molecular phenotypes have been associated with aggressive behavior, and some of these markers are related with proteoglycans, which in turn show alterations in CRC. Small leucine-rich proteoglycans (SLRPs) are a family of molecules encoded by18 genes that may appear coupled to different glycosaminoglycan chains ––including chondroitin/dermatan or keratan sulphate–– or not, depending on the specific species. They are ubiquitously expressed in extracellular matrices, and it’s been described their role in organ size and shape regulation during embryonic development. This study aims to investigate the expression patterns of SLRPs in CRC depending on the PTL. Methods: A transcriptomic approach was carried out by using qPCR to analyze SLRP core protein transcriptions in 32 tumor specimens and their respective healthy tissue: 12 right-sided & 20 left-sided. When significant differences were detected, immunohistochemical techniques were used to enhance the test. Results: While right-sided (R) CRC displayed significant alterations in 2 genes (biglycan BGN overexpression p = 0.015, osteoglycin OGN underexpression p = 0.048), left-sided (L) showed differences in 5 genes (BGN overexpression p = 0.0019 and underexpression of OGN p = 0.0016, prolargin PRELP p = 0.0049, chondroadherin CHAD p = 0.0180 and podocan PODN p = 0.0061). In L tumors CHAD was the most affected gen underexpressed by 16 times, while in R it was present in only 50% of healthy tissue. Transcripts for opticin and nyctalopin were not detected in most patients regardless of PTL. Lumican, decorin, keratocan, asporin, ECM2, fibromodulin, tsukushi, osteoadherin, osteomodulin, epiphycan and PODN-like 1 were detected with no significant differences compared to healthy tissue. Conclusions: Normal mucosa of the large bowel expresses most SLRP. BGN and OGN seem to be dysregulated in both L and R CRC, but CHAD, PRELP and PODN appear to show differences only in L CRC. These alterations could be related to the interaction with different ligands and modulation of homeostasis.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 652-652
Author(s):  
Maria Del Pilar Solis Hernandez ◽  
Olivia Pilar García-Suárez ◽  
Ivan Fernández-Vega ◽  
Luis M Quirós ◽  
Beatriz García

652 Background: Colorectal cancer (CRC) is a heterogeneous disease, and there are anatomic, functional and molecular differences between the tumors of the proximal and distal colorectum. Various molecular phenotypes have been associated with aggressive subtypes in these pathologies, and several of these markers show a relationship with proteoglycans, which in turn show significant alterations in colon tumors, which affect both their core proteins and their glycosaminoglycan chains. Small leucine-rich proteoglycans (SLRPs) constitute a family of molecules encoded by 18 distinct genes. They are grouped into five classes and may appear coupled to different glycosaminoglycan chains ––including chondroitin/dermatan sulfate or keratan sulphate–– or not, depending on the specific species. They are ubiquitously expressed in extracellular matrices, and have been found involved in the regulation of organ size and shape during embryonic development. In this study we investigate the expression patterns of SLRPs in right-sided CRCs. Methods: A transcriptomic approach was used, employing qPCR to analyze SLRP core protein transcriptions. Immunohistochemical techniques were also used to analyze tissue expression of particular genes showing significant expression differences of potential interest. Results: Only two proteins displayed significant alterations: biglycan appeared overexpressed approximately 4 fold (p = 0.015), and osteoglycin decreased about 4 fold (p = 0.05). Transcripts for epiphycan, opticin, nyctalopin and podocan-like 1 were not detected in most patients, while chondroadherin was detected in 50% of healthy tissues but not in CRCs. Expression of lumican, decorin, keratocan, asporin, ECM2, fibromodulin, PRELP, tsukushi, podocan and osteoadherin was detected, but with no significant differences compared to healthy tissue. Conclusions: Normal mucosa of the large bowel expresses most SLRPs, and two, biglycan and osteoglycin, appeared altered in right-sided CRCs. These alterations could be related to binding of different ligands and modulation of homeostasis.


Sign in / Sign up

Export Citation Format

Share Document