Different small leucine-rich proteoglycans expression pattern by tumor location in colorectal cancer.

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 ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Core Protein ◽  
Expression Patterns ◽  
Normal Mucosa ◽  
Tumor Location ◽  
Healthy Tissue ◽  
Test Results ◽  
Molecular Phenotypes ◽  
Immunohistochemical Techniques ◽  
Specific Species

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.

Alterations in small leucine-rich proteoglycans in right-sided colorectal cancer.

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
Keyword(s):  
Colorectal Cancer ◽  
Dermatan Sulfate ◽  
Core Protein ◽  
Expression Patterns ◽  
Tissue Expression ◽  
Normal Mucosa ◽  
Core Proteins ◽  
Molecular Phenotypes ◽  
Immunohistochemical Techniques ◽  
Specific Species

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.

Small leucine-rich proteoglycans expression in colorectal cancer: Differences by primary tumor location.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 721-721
Author(s):  
Maria Del Pilar Solis Hernandez ◽  
Natalia Perez Lopez ◽  
Yolanda Garcia Mesa ◽  
Ivan Fernandez-Vega ◽  
Olivia García-Suárez ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Primary Tumor ◽  
Core Protein ◽  
Tumor Location ◽  
Small Sample ◽  
Rank Test ◽  
Test Results ◽  
Colorectal Tissue ◽  
Kaplan Meier ◽  
Fresh Frozen

721 Background: SLRP are present in normal and tumor colorectal tissue, with different patterns of expression, being predominant in L CRC. However, due to the small sample the differences observed in survival were no statistically significative. These alterations could be related to interactions at the extracellular matrix level. Further prospective and larger analysis are needed for a better comprehension of tumor microenvironment. Aims: To describe SLRP expression pattern by PTL and survival rate. Methods: 32 tumor specimens and their respective healthy tissue (fresh frozen tissue) from primary tumor surgery from the local biobank: 12 right-sided (R) & 20 left-sided (L) CRC. Transcriptomic approach to analyze SLRP core protein transcriptions using RT-PCR in Those with significative differences were confirmed by immunohistochemistry. Survival analysis was performed using Kaplan-Meier curves and log rank test. Results: Both sides showed BGN 2-fold overexpression (R p = 0.015, L p = 0.001) and OGN decreased 4-3-fold (R p = 0.038, L p < 0.001). PODNL was only expressed in tumor tissue. Additionally, alterations in other 4 genes in L CRC: PODN 2-fold p = 0.003, CHAD 4-fold p = 0.017, DCN 2fold p = 0.047 and PRELP 3-fold p = 0.003. EPYC was only expressed in 50% of L CRC. No difference in ASPN, FMOD, LUM, ECM2, KERA, OMD, TSK. Neither it was in PRELP for L CRC nor EPYC and DCN in R CRC. No expression of OPTC was found. No significative differences in survival were found. Median relapse-free survival (RFS) was 25 months (mo), 10.75 mo R CRC and 19.47mo L CRC. BGN overexpression (44%) was related with worse RFS (14 vs 19mo), better in L CRC (12 vs 19mo). OGN decrease (17%) showed better RFS (40 vs 16mo) favoring L CRC (21 vs 17mo). Overall survival displayed a similar behavior. Conclusions: SLRP are present in normal and tumor colorectal tissue, with different patterns of expression, being predominant in L CRC. However, due to the small sample the differences observed in survival were no statistically significative. These alterations could be related to interactions at the ECM level. Further prospective and larger studies are needed for a better comprehension of tumor microenvironment.

scholarly journals Differential Expression of Ribosomal Proteins in Human Normal and Neoplastic Colorectum

2003 ◽  
Vol 51 (5) ◽  
pp. 567-573 ◽  
Author(s):  
Hide Kasai ◽  
Daita Nadano ◽  
Eiko Hidaka ◽  
Kayoko Higuchi ◽  
Masatomo Kawakubo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ribosomal Proteins ◽  
Protein Biosynthesis ◽  
Secretory Granules ◽  
Expression Patterns ◽  
Normal Mucosa ◽  
Cellular Processes ◽  
Colorectal Mucosa ◽  
Colorectal Cancer Cells ◽  
Mucosal Cells

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.

scholarly journals Elevated expression of AGGF1 predicts poor prognosis and promotes the metastasis of colorectal cancer

2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He
Keyword(s):  
Colorectal Cancer ◽  
Distant Metastasis ◽  
Expression Patterns ◽  
Mrna Level ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
Expression Level ◽  
Angiogenic Factor ◽  
Migration And Invasion ◽  
Aberrant Expression

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.

scholarly journals Elevated expression of AGGF1 predicts poor prognosis and promotes the metastasis of colorectal cancer

2019 ◽  
Author(s):  
Xin Zhang ◽  
Huimin Sun ◽  
Wanyuan Chen ◽  
Xianglei He
Keyword(s):  
Colorectal Cancer ◽  
Distant Metastasis ◽  
Expression Patterns ◽  
Mrna Level ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
Expression Level ◽  
Angiogenic Factor ◽  
Migration And Invasion ◽  
Aberrant Expression

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.

scholarly journals Neonatal Nav1.5 Protein Expression in Human Colorectal Cancer: Immunohistochemical Characterization and Clinical Evaluation

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3832
Author(s):  
Elena Lastraioli ◽  
Scott P. Fraser ◽  
R. Mine Guzel ◽  
Jessica Iorio ◽  
Lapo Bencini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Expression Patterns ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Normal Mucosa ◽  
Free Survival ◽  
Human Carcinomas ◽  
Clinical Biomarker ◽  
High Level

Voltage-gated Na+ channels (VGSCs) are expressed widely in human carcinomas and play a significant role in promoting cellular invasiveness and metastasis. However, human tissue-based studies and clinical characterization are lacking. In several carcinomas, including colorectal cancer (CRCa), the predominant VGSC is the neonatal splice variant of Nav1.5 (nNav1.5). The present study was designed to determine the expression patterns and clinical relevance of nNav1.5 protein in human CRCa tissues from patients with available clinicopathological history. The immunohistochemistry was made possible by the use of a polyclonal antibody (NESOpAb) specific for nNav1.5. The analysis showed that, compared with normal mucosa, nNav1.5 expression occurred in CRCa samples (i) at levels that were significantly higher and (ii) with a pattern that was more delineated (i.e., apical/basal or mixed). A surprisingly high level of nNav1.5 protein expression also occurred in adenomas, but this was mainly intracellular and diffuse. nNav1.5 showed a statistically significant association with TNM stage, highest expression being associated with TNM IV and metastatic status. Interestingly, nNav1.5 expression co-occurred with other biomarkers associated with metastasis, including hERG1, KCa3.1, VEGF-A, Glut1, and EGFR. Finally, univariate analysis showed that nNav1.5 expression had an impact on progression-free survival. We conclude (i) that nNav1.5 could represent a novel clinical biomarker (‘companion diagnostic’) useful to better stratify CRCa patients and (ii) that since nNav1.5 expression is functional, it could form the basis of anti-metastatic therapies including in combination with standard treatments.

Estrogen and Progesterone Receptors in Colorectal Cancer and Surrounding Mucosa

2001 ◽  
Vol 16 (4) ◽  
pp. 262-267 ◽  
Author(s):  
P. Raigoso ◽  
L. Sanz ◽  
F. Vizoso ◽  
B. Llana ◽  
I. Quintela ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Survival ◽  
Progesterone Receptors ◽  
Normal Mucosa ◽  
Tumor Location ◽  
Histological Differentiation ◽  
Er Positive ◽  
The Mean ◽  
Low Levels

In this prospective study we have quantified by means of ELISA-methods the cytosolic content of estrogen (ER) and progesterone receptors (PgR) in tumoral tissue and paired normal mucosa from 163 patients with resectable colorectal cancer. Survival analysis was performed in a subgroup of 120 patients and the mean follow-up period was 24.9 months. The cutoff for ER and PgR levels was set at 1 fmol/mg protein. On the basis of this cutoff 20.9% of the cancers were ER positive and 25.8% were PgR positive; normal adjacent tissue presented ER in 18.4% and PgR in 24.5%. Our results did not show any significant correlation between ER and PgR levels in neoplastic tissues. Howewer, a correlation was found in normal mucosa samples (p=0.02). Statistical analysis showed that there was no correlation between tumor ER and PgR content and patient age or sex, tumor location, Dukes’ stage, histological differentiation, DNA ploidy status and S-phase fraction. Furthermore, the results did not show any statistical differences in relapse-free and overall survival curves calculated for patients classified according to the hormone receptor content of their tumors. ER and PgR were detected at low levels in normal and neoplastic colorectal tissues without any significant relationship to either clinicopathological tumor characteristics or patient outcome. Their possible role in colorectal cancer remains to be elucidated.

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