scholarly journals Subcellular localization of HMGB1 in colorectal cancer impacts on tumor grade and survival prognosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chao-Qun Wang ◽  
Bi-Fei Huang ◽  
Yan Wang ◽  
Chih-Hsin Tang ◽  
Hong-Chuan Jin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Adenoma ◽  
Prognostic Significance ◽  
Tumor Grade ◽  
Hmgb1 Protein ◽  
Survival Prognosis ◽  
Tissue Samples ◽  
Colorectal Tissue ◽  
Hmgb1 Expression ◽  
Normal Colorectal Tissue

Abstract The high-mobility group box-1 (HMGB1) protein is implicated in the development of various cancers and their proliferation. According to its function, HMGB1 shuttles between the cell nucleus and cytoplasm, assisting with nucleosome stabilization and gene transcription, or localizing in the cell membrane for outgrowth. The clinicopathologic and prognostic significance of these different subcellular locations and their correlation has been unclear in colorectal cancer (CRC). We found significantly higher rates of nuclear HMGB1 expression in CRC and colorectal adenoma tissue samples (84.0% and 92.6%, respectively) than in normal colorectal tissue (15.0%) and a significantly higher rate of positive cytoplasmic HMGB1 expression in CRC tissue (25.2%) compared with colorectal adenoma (11.8%) and normal colorectal tissue (0.0%). Positive cytoplasmic HMGB1 expression was associated with high-grade CRC, a poor prognosis, and was negatively correlated with strongly positive nuclear HMGB1 expression in CRC tissue specimens (r = – 0.377, P = 0.000). CRC patients with strongly positive nuclear HMGB1 expression had a better survival prognosis than other CRC patients. Preventing nuclear plasma translocation of HMGB1 may be a new strategy for CRC management.

scholarly journals Distribution of 5-Hydroxymethylcytosine in Different Human Tissues

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Weiwei Li ◽  
Min Liu
Keyword(s):  
Colorectal Cancer ◽  
Human Tissues ◽  
Colorectal Tissue ◽  
First Time ◽  
Normal Colorectal Tissue ◽  
Different Tissues

5-hydroxymethylcytosine (5-hmC) is a modified form of cytosine recently found in mammalians and is believed, like 5-methylcytosine, to also play an important role in switching genes on and off. By utilizing a newly developed 5-hmC immunoassay, we determined the abundance of 5-hmC in human tissues and compared 5-hmC states in normal colorectal tissue and cancerous colorectal tissue. Significant differences of 5-hmC content in different tissues were observed. The percentage of 5-hmC measured is high in brain, liver, kidney and colorectal tissues (0.40–0.65%), while it is relatively low in lung (0.18%) and very low in heart, breast, and placenta (0.05-0.06%). Abundance of 5-hmC in the cancerous colorectal tissues was significantly reduced (0.02–0.06%) compared to that in normal colorectal tissues (0.46–0.57%). Our results showed for the first time that 5-hmC distribution is tissue dependent in human tissues and its abundance could be changed in the diseased states such as colorectal cancer.

scholarly journals Systematic Analysis of the Clinical Significance of Hyaluronan-Mediated Motility Receptor in Colorectal Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Yan-ping Tang ◽  
Yi-xin Yin ◽  
Ming-zhi Xie ◽  
Xin-qiang Liang ◽  
Ji-lin Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Prognostic Significance ◽  
Human Colon ◽  
Blood Levels ◽  
Epithelial Cell Line ◽  
Healthy Controls ◽  
Systematic Analysis ◽  
Tissue Samples ◽  
Blood Samples

Background: The role of hyaluronan-mediated motility receptor (HMMR) in colorectal cancer (CRC) remains unclear. The present study aimed to explore the association of HMMR with the development and prognosis of CRC using sequence datasets, clinical tissues, blood samples, and cell lines.Methods: CRC datasets were downloaded from TCGA and GEO databases. Forty CRC tissue samples, 120 CRC blood samples, and 100 healthy controls were collected. Four CRC cell lines (HCT116, HT-29, LoVo, and SW480) and one normal human colon mucosal epithelial cell line (NCM460) were cultured. RT-qPCR was used to determine the expression of HMMR in the tissues and cell lines. ELISA was used to measure HMMR levels in the blood samples.Results: The expression of HMMR was significantly increased in CRC tissues than in corresponding adjacent tissues based on TCGA and GEO datasets, and clinical CRC tissues. No associations were found between the expression of HMMR and the TNM stage or other clinical parameters. The expression of HMMR varied in different CRC cell lines. The blood levels of HMMR tended to be higher in patients with CRC than in healthy controls. TCGA and GEO datasets showed inconsistent results regarding the association of HMMR expression with the survival of patients with CRC.Conclusion: The expression of HMMR is increased in CRC tissues but not in the blood. The expression of HMMR is independent of CRC development and has no prognostic significance in patients with CRC.

scholarly journals Prognostic Value of Circulating KRAS2 Gene Mutations in Colorectal Cancer with Distant Metastases

2006 ◽  
Vol 21 (4) ◽  
pp. 223-228 ◽  
Author(s):  
C. Trevisiol ◽  
F. Di Fabio ◽  
R. Nascimbeni ◽  
L. Peloso ◽  
C. Salbe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Primary Treatment ◽  
Tissue Samples ◽  
Primary Tumors ◽  
Mutational Status ◽  
Stage D ◽  
Related Survival

While tissue KRAS2 mutations have been extensively investigated, the role of circulating mutant KRAS2 gene in patients with colorectal carcinoma remains obscure. The aim of the present study was to explore the prognostic significance of circulating KRAS2 gene mutational status in subjects undergoing primary treatment for colorectal cancer. Codon 12 KRAS2 mutations were examined in DNA samples extracted from the serum of 86 patients with colorectal cancer and were compared with the KRAS2 status of their primary tumors. Tissue and serum KRAS2 status was compared with other clinicopathological variables (including CEA and CA 19-9 levels) and with cancer-related survival. KRAS2 mutations were found in tissue samples of 28 patients (33%); serum KRAS2 mutations were detected in 10 of them (36%). Serum KRAS2 status was significantly associated with Dukes' stage D (p=0.001) and with preoperative CA 19-9 levels (p=0.01). At multivariate analysis, cancer-related survival was associated with Dukes' stage (p<0.0001), CEA level (p=0.02), and mutant circulating KRAS2 (p=0.01). All 7 stage D patients with serum KRAS2 mutations died of the disease within 24 months of primary treatment; cancer-related survival was significantly better in 9 stage D patients without serum KRAS2 mutations, with 5 patients (56%) alive after 24 months and 1 patient (13%) alive after 44 months. Residual disease after surgery was evident in all 7 stage D patients with mutant circulating KRAS2, and in 5 out of 9 stage D patients without serum mutations. Serum KRAS2 status may impact substantially on the management of stage D colorectal carcinoma, since it appears to correlate with prognosis in this patient subgroup.

scholarly journals Metadherin (MTDH) Overexpression Significantly Correlates with Advanced Tumor Grade and Stages among Colorectal Cancer Patients

2021 ◽  
Author(s):  
Aimen Sultan ◽  
Namood-e Sahar ◽  
Syeda Kiran Riaz ◽  
Javeria Qadir ◽  
Shahzad Hussain Waqar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Tumor Tissue ◽  
Tumor Grade ◽  
Ki 67 ◽  
Core Element ◽  
Age And Gender ◽  
Tissue Samples ◽  
Advanced Tumor ◽  
And Gender

Abstract BackgroundColorectal cancer is the 4th leading cause of cancer related deaths affecting both men and women worldwide. In the present study, any probable role of MTDH mRNA expression in CRC tumorigenesis was explored using both discovery and validation cohorts. Methods and resultsAfter prior ethical and biosafety approvals, tumor tissue samples along with their adjacent controls were collected for this study from Pakistani patients diagnosed with colorectal cancer. RNA was isolated using Trizol reagent, followed by cDNA synthesis. Transcript analysis of MTDH was performed by using qPCR. Moreover, genome-wide expression of MTDH was also determined through micro-array data analysis using BRB- Array Tools software. MTDH expression was significantly high in tumor tissue samples (p<0.05) compared to their respective controls. Likewise, results of microarray analysis also revealed overamplification of MTDH in tumor samples as compared to controls. Expression of MTDH was also found to be positively correlated with KI-67 index (p<0.05) and were observed to be significantly upregulated in advance tumor grade (p< 0.05) and stage (p< 0.05). However, no association of MTDH overexpression with age and gender could be established. ConclusionHence, it can be concluded that MTDH is a core element that plays a pivotal role in colorectal tumorigenesis irrespective of patient’s age and gender. Molecular insight into the tumor microenvironment revealed MTDH as a niche, representing distinctive framework for cancer progression, thus, making it an innovative target strategy for colorectal cancer treatment.

scholarly journals Expression of ERα, ERβ and Co-Regulator PELP1/MNAR in Colorectal Cancer: Prognostic Significance and Clinicopathologic Correlations

2009 ◽  
Vol 31 (3) ◽  
pp. 235-247
Author(s):  
Petros D. Grivas ◽  
Vassiliki Tzelepi ◽  
Georgia Sotiropoulou-Bonikou ◽  
Zinovia Kefalopoulou ◽  
Athanasios G. Papavassiliou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Cells ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Normal Mucosa ◽  
Colorectal Carcinogenesis ◽  
Colorectal Tumorigenesis ◽  
Free Survival ◽  
Colorectal Tissue ◽  
Favorable Prognostic Factor

Background: Estrogen receptor β (ERβ) is abundantly expressed in colorectal tissue, but its role in colorectal carcinogenesis remains elusive. ER novel co-regulator, proline-, glutamic acid- and leucine-rich protein 1 (PELP1/MNAR) has been characterized, but its expression in colorectal carcinomas has not been investigated.Methods: ERα, ERβ and PELP1/MNAR protein expression were evaluated by immunohistochemistry in colorectal normal mucosa, adenomas and adenocarcinomas from 113 patients with colorectal cancer.Results: ERα expression is extremely rare in colorectal tissue and its expression does not appear to be associated with colorectal carcinogenesis. ERβ and PELP1/MNAR were detected in the nucleus of epithelial, endothelial, inflammatory, smooth muscle cells and myofibroblasts. When intensity of staining was taken into account, the expression of both proteins was significantly increased in epithelial cells of carcinomas compared to normal mucosa. ERβ expression in epithelial cells was correlated with decreased disease progression – free survival. PELP1/MNAR overexpression in epithelial cells was found to be an independent favorable prognostic factor. Additionally, the expression of both proteins was significantly increased in stromal myofibroblasts of carcinomas compared to adenomas and normal mucosa.Conclusion: ERβ and PELP1/MNAR appear to be involved in colorectal tumorigenesis and might have prognostic significance.

scholarly journals VEGF Expression in Colorectal Cancer Metastatic Lymph Nodes: Clinicopathological Correlation and Prognostic Significance

2020 ◽  
Vol 2 (3) ◽  
pp. 267-280
Author(s):  
Inês Mazeda ◽  
Sandra F. Martins ◽  
Eduardo A. Garcia ◽  
Mesquita Rodrigues ◽  
Adhemar Longatto
Keyword(s):  
Colorectal Cancer ◽  
Primary Tumor ◽  
Mutual Influence ◽  
Prognostic Significance ◽  
Metastatic Progression ◽  
Vegf Expression ◽  
Tissue Samples ◽  
New Information ◽  
Patient Prognosis ◽  
The Relationship

Background: Angiogenesis plays an important role in colorectal cancer (CRC) tumorigenesis and metastatic progression. Methods: The present series consisted of CRC lymph node metastasis (LNM) tissue samples from 210 patients. Archival paraffin embedded LNM tissue were used to build up tissue microarray blocks and VEGF expression was immunohistochemically assessed. Results: VEGF-A and VEGF-C are overexpressed in LNM. VEGF-A was associated with patient age (p < 0.001), and VEGFR-2 and VEGFR-3 with CRC relapse (p = 0.032; p = 0.030, respectively). VEGF-C positivity was associated with VEGFR-3 positivity (p = 0.031), and VEGF-D with VEGFR-2 and VEGFR-3 (p ≤ 0.001). Matching the expression in LNM with CRC, in CRC VEGF-A positivity associates with VEGF-A, VEGF-C, VEGF-D, VEGF-R2, VEGF-R3 positivity in LNM; CRC VEGF-C with VEGF-D, VEGFR-2, VEGFR-3; CRC VEGFR-2 with VEGF-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3; CRC VEGFR-3 with VEGF-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3 in LNM. Conclusion: This study provides new information, revealing that VEGF family expression is increased in LNM. The association between the expression of VEGFR-2 and VEGFR-3 in LNM with CRC relapse reveals its impact on patient prognosis. Interesting data were found when the relationship between these proteins in primary tumor and their metastasis, were analyzed; VEGFA positivity in primary tumor is positively related to VEGF-A, VEGF-C, VEGF-D, VEGFR-2 and VEGFR-3 in their respective LNM suggesting mutual influence.

scholarly journals Correlation Between Baseline Osteoprotegerin Serum Levels and Prognosis of Advanced-Stage Colorectal Cancer Patients

2018 ◽  
Vol 45 (2) ◽  
pp. 605-613 ◽  
Author(s):  
Enrico De Toni ◽  
Dorothea Nagel ◽  
Alexander B. Philipp ◽  
Andreas Herbst ◽  
Isabel Thalhammer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pilot Study ◽  
Life Expectancy ◽  
Prognostic Significance ◽  
Cancer Control ◽  
Stage Iv ◽  
Immunohistochemical Analysis ◽  
Serum Samples ◽  
Tissue Samples ◽  
Baseline Serum

Background/Aims: Osteoprotegerin (OPG) is a soluble receptor of the pro-apoptotic cytokine TRAIL which is thought to contribute to tumour development by inhibiting apoptosis or affecting other aspects of tumour biology, including cell proliferation and immune response. Although immunohistochemical studies suggest that OPG correlates with survival in metastatic colorectal cancer (mCRC), only scarce data are available on serum OPG in CRC patients. Methods: In this pilot study, we assessed the prognostic significance of serum OPG and CEA (Carcinoembryonic antigen) in 81 patients with UICC (Union for International Cancer Control) stage-IV mCRC. OPG was additionally assessed by immunohistochemistry in primary tissue samples from 33 patients of the same cohort. Results: Baseline serum OPG correlated with CEA (r=0.36, p=0.0011), but independently predicted survival of mCRC patients. Life expectancy was poorer in patients with OPG levels above the median concentration of 51ng/ml (median overall survival [95% confidence interval] 1.8 years [1.3-3.0] vs. 1.0 [0.7-1.2] p=0.013). Patients with high levels of both OPG and CEA had an even poorer life expectancy vs. low-OPG/low-CEA patients (0.9 years [0.6-1.5] vs. 3 years [1.2-4.4], p=0.015), indicating that CEA and OPG have additive prognostic significance. Immunohistochemical analysis of OPG failed to show a correlation between OPG staining and survival (p=0.055) or OPG concentration from matched serum samples. Conclusions: This pilot study provides evidence of independent prognostic significance of serum OPG in patients with advanced mCRC and warrants its further prospective validation.

scholarly journals Prognostic significance of tumor-induced angiogenesis in colorectal cancer

2003 ◽  
Vol 56 (5-6) ◽  
pp. 263-268 ◽  
Author(s):  
Attila Fenyvesi
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Microvessel Density ◽  
Antiangiogenic Therapy ◽  
Prognostic Significance ◽  
Predictive Marker ◽  
Tumor Grade ◽  
Tumor Type ◽  
Microvessel Count ◽  
Stage Of Disease

Introduction Tumor-induced angiogenesis is a central pathogenic step in the process of tumor growth, invasion and metastasis. The aim of this study was to analyze the quantitative expression of angiogenesis in colorectal carcinoma and to determine if and how angiogenesis correlates with other clinicopathologic factors and prognosis. Material and methods This study included 40 patients who underwent curative resection of colorectal cancer at the Department of Surgery of the Senta General Hospital with complete 5 years follow-up or till death. Microvessels were identified immunohistochemically using monoclonal CD31 antibodies. The microvessel count was assessed by means of stereology with test grid M42, as well as vascular surface density in the stromal volume at the invasive front of colorectal cancer. Results Tumor-induced angiogenesis count of colorectal carcinomas statistically significantly correlated with stage of disease and histologic tumor grade There was no significant correlation between intratumoral microvessel density and sex and age of patients, localization and histologic tumor type Five-year survival rate in patients with hypervascular colorectal tumors was statistically significantly lower than in patients with hypovascular tumors Thus, microvessel density in colorectal cancer is an independent prognostic factor, but its significance is less than the importance concerning stage of disease and histologic grade of tumor. Conclusions Intratumoral microvessel density quantification in histologic specimens of colorectal carcinoma reflects the biological malignant potential of tumors and may be a useful additional predictive marker. Assessment of intratumoral microvessel count might be used for determining the pathologic stage when adjuvant therapy is concerned. Microvessel density in tumor specimens is valuable in stratifying patients in planning appropriate adjuvant and antiangiogenic therapy after surgery.

scholarly journals High frequency of enterotoxigenic Bacteroides fragilis and Enterococcus faecalis in the paraffin-embedded tissues of Iranian colorectal cancer patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nasibeh Khodaverdi ◽  
Habib Zeighami ◽  
Ahmad Jalilvand ◽  
Fakhri Haghi ◽  
Negar Hesami
Keyword(s):  
Colorectal Cancer ◽  
Enterococcus Faecalis ◽  
Copy Number ◽  
Bacteroides Fragilis ◽  
Control Group ◽  
Cancer Tissue ◽  
Healthy Controls ◽  
Tissue Samples ◽  
Colorectal Tissue ◽  
Significant Difference

Abstract Background The association between specific bacteria and colorectal cancer (CRC) has been proposed. Only a few studies have, however, investigated this relationship directly in colorectal tissue with conflicting results. So, we aimed to quantitate Streptococcus gallolyticus, Fusobacterium spp, Enterococcus faecalis and enterotoxigenic Bacteroides fragilis (ETBF) in formalin-fixed and paraffin-embedded (FFPE) colorectal tissue samples of Iranian CRC patients and healthy controls. Methods A total of 80 FFPE colorectal tissue samples of CRC patients (n = 40) and healthy controls (n = 40) were investigated for the presence and copy number of above bacterial species using quantitative PCR. Relative quantification was determined using ΔΔCT method and expressed as relative fold difference compared to reference gene. Results Relative abundance and copy number of E. faecalis and ETBF were significantly higher in CRC samples compared to control group. E. faecalis was more prevalent than ETBF in tumor samples. Frequency of ETBF and E. faecalis in late stages (III/IV) of cancer was significantly higher than early stages (I/II). We did not detect a significant difference in abundance of S. gallolyticus and Fusobacterium spp between two groups. Conclusion Our study revealed the higher concentration of E. faecalis and ETBF in FFPE samples of CRC patients than controls. However, additional investigations on fecal and fresh colorectal cancer tissue samples are required to substantiate this correlation.

Differentiation of Tumour from Normal Colorectal Tissue by SELDI-MS Protein Profiling

Endoscopy ◽  
2004 ◽  
Vol 36 (05) ◽  
Author(s):  
AM Lennon ◽  
D Stuart ◽  
AC Tan ◽  
E Fox ◽  
KS Sheahan ◽  
...  
Keyword(s):  
Protein Profiling ◽  
Colorectal Tissue ◽  
Normal Colorectal Tissue
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