Use of anti-neuropilin 1, 2 antibodies to predict colorectal cancer prognosis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15111-e15111
Author(s):  
A. Takeda
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Lymphatic Vessels ◽  
Constitutive Expression ◽  
Venous Invasion ◽  
Immunohistochemical Analysis ◽  
Predictive Marker ◽  
Lymphatic Invasion ◽  
Cancer Prognosis ◽  
Cancer Tissues

e15111 Background: Neuropilin (NRP) was initially described as non-tyrosine kinase receptors for neuron guidance factor belonging to the Semaphorin family. Two subtypes, NRP-1 and NRP-2 have been isolated. Neuropilins are widely expressed not only normal developing tissues but also several types of tumor cells. It was reported that the expression of NRP-1 is increased by VEGF, mediated through VEGFR-2, which correlates with tumor growth and invasiveness in colorectal cancer. NRP-2 knockout mice studies showed marked deficits in the development of small lymphatic vessels and its function was associated with the formation of lymphatic network, but the role of NRP-2 in colorectal cancer remains unknown. Methods: We have newly established two useful anti- Neuropilin antibodies against CUB domains of NRP-1 and cytoplasmic domains of NRP-2. In recent study, we have analyzed the expression of NRP-1 and NRP-2 in some cultured cell lines by western blot and the clinicopathological significance in colorectal cancer. Tissues samples were obtained from 72 primary colorectal adenocarcinomas (colon:39 cases, rectum:33 cases). The pathologic stage were as follows; stageI:10 patients, II:25 patients, III:26 patients and IV:11 patients. NRP-1 and NRP-2 gene expression was evaluated by RT- PCR, which was compared with immunohistochemical examination of colorectal cancer tissues. Constitutive expression of NRP-1 was detected in PC3, HT29, PC9 and PC13 cell lines and NRP-2 in HT29, PC3 and PC9. Results: There was significant correlation between NRP-1 and -2 protein expression and both of mRNA expression. The expression of NRP-1 showed apparent correlation with liver metastasis (p=0.027) and venous invasion (p=0.0025), while NRP-2 expression was correlated with lymph node metastasis (0.001) and lymphatic invasion (0.039) by immunohistochemical analysis. The post-surgical treatment observation revealed that patients with co- expression of NRP-1 and NRP-2 were significantly correlated with poorer prognosis than both NRP-1 and NRP-2 negative patients (p=0.035). Conclusions: These results suggest that NRP-1 acts as angiogenesis factor and NRP-2 acts lymphangiogenesis factor, both of them are useful predictive marker in colorectal cancer. No significant financial relationships to disclose.

scholarly journals Pure Well-Differentiated Adenocarcinoma Is a Safe Factor for Lymph Node Metastasis in T1 and T2 Colorectal Cancer: A Pilot Study

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Naohisa Yoshida ◽  
Masayoshi Nakanishi ◽  
Ken Inoue ◽  
Ritsu Yasuda ◽  
Ryohei Hirose ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Venous Invasion ◽  
Lymphatic Invasion ◽  
Clinicopathological Factors ◽  
Node Metastasis ◽  
Kappa Value ◽  
T1 And T2 ◽  
Well Differentiated

Background and Aims. Various risk factors for lymph node metastasis (LNM) have been reported in colorectal T1 cancers. However, the factors available are insufficient for predicting LNM. We therefore investigated the utility of the new histological factor “pure well-differentiated adenocarcinoma” (PWDA) as a safe factor for predicting LNM in T1 and T2 cancers. Materials and Methods. We reviewed 115 T2 cancers and 202 T1 cancers in patients who underwent surgical resection in our center. We investigated the rates of LNM among various clinicopathological factors, including PWDA. PWDA was defined as a lesion comprising only well-differentiated adenocarcinoma. The consistency of the diagnosis of PWDA was evaluated among two pathologists. In addition, 72 T1 cancers with LNM from 8 related hospitals over 10 years (2008–2017) were also analyzed. Results. The rates of LNM and PWDA were 23.5% and 20.0%, respectively, in T2 cancers. Significant differences were noted between patients with and without LNM regarding lymphatic invasion (81.5% vs. 36.4%, p<0.001), poor histology (51.9% vs. 19.3%, p=0.008), and PWDA (3.7% vs. 25.0%, p=0.015). The rates of LNM and PWDA were 8.4% and 36.1%, respectively, in T1 cancers. Regarding the 73 PWDA cases and 129 non-PWDA cases, the rates of LNM were 0.0% and 13.2%, respectively (p<0.001). Among the 97 cases with lymphatic or venous invasion, the rates of LNM in 29 PWDA cases and 68 non-PWDA were 0% and 14.7%, respectively (p=0.029). The agreement of the two pathologists for the diagnosis of PWDA was acceptable (kappa value > 0.5). A multicenter review showed no cases of PWDA among 72 T1 cancers with LNM. Conclusions. PWDA is considered to be a safe factor for LNM in T1 cancer.

scholarly journals MiR-382 functions as tumor suppressor and chemosensitizer in colorectal cancer

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Hui Yao ◽  
Dong Xia ◽  
Zong-lin Li ◽  
Lei Ren ◽  
Ming-ming Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Critical Role ◽  
Colorectal Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Interacting Protein ◽  
Colorectal Cancer Cell Lines ◽  
Cancer Tissues

Abstract Increasing evidence suggests that microRNAs (miRNAs) play a critical role in tumorigenesis. Decreased expression of miR-382 has been observed in various types of cancers. However, the biological function of miR-382 in colorectal cancer (CRC) is still largely unknown. Here, we found that miR-382 was down-regulated in human colorectal cancer tissues and cell lines associated with it. MiR-382 inhibited colorectal cancer cell proliferation, migration, invasion, and enhance chemosensitivity. Furthermore, we identified Krüppel-like factor 12 (KLF12) and homeodomain-interacting protein kinase 3 (HIPK3) as the target of miR-382, and miR-382 rescued the promotion effect of KFL12 on migration and enhanced chemosensitivity in colorectal cancer cell lines. Collectively, these findings revealed that miR-382 inhibits migration and enhances chemosensitivity by targeting KLF12 and HIPK3 in colorectal cancer. These findings might serve as a tumor suppressor in CRC.

scholarly journals Claudin-1 Is a Valuable Prognostic Biomarker in Colorectal Cancer: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Didi Zuo ◽  
Jiantao Zhang ◽  
Tao Liu ◽  
Chao Li ◽  
Guang Ning
Keyword(s):  
Colorectal Cancer ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Venous Invasion ◽  
Lymphatic Invasion ◽  
Cochrane Library ◽  
Test Sequence ◽  
Tumor Type ◽  
The Stability

Background. Claudin-1 plays an important part in maintaining the mucosal structures and physiological functions. Several studies showed a relationship between claudin-1 and colorectal cancer (CRC), but its prognostic significance is inconsistent. This meta-analysis assessed the prognostic value and clinical significance of claudin-1 in CRC. Materials and Methods. We retrieved eligible studies from PubMed, Cochrane Library, Embase, and Web of Science databases before February 10, 2020. The hazard ratio (HR) with 95% confidence interval (CI) was applied to assess the correlation between claudin-1 and prognosis and clinical features. Heterogeneity was assessed by the Cochran Q test and I-square (I2), while publication bias was evaluated by the Begg test and Egger test. Test sequence analysis (TSA) was used to estimate whether the included studies’ number is sufficient. The stability of the results was judged by sensitivity analysis. Metaregression was utilized to explore the possible covariance which may impact on heterogeneity among studies. Results. Eight studies incorporating 1704 patients met the inclusion criteria. Meta-analysis showed that the high expression of claudin-1 was associated with better overall survival (HR, 0.46; 95% CI, 0.28–0.76; P=0.002) and disease-free survival (HR, 0.44; 95% CI, 0.29–0.65; P=0.003) in CRC. In addition, we found that claudin-1 was related to the better tumor type (n=6; RR, 0.60; 95% CI, 0.49–0.73; P<0.00001), negative venous invasion (n=4; RR, 0.81; 95% CI, 0.70–0.95; P=0.001), and negative lymphatic invasion (n=4; RR, 0.83; 95% CI, 0.74–0.92; P=0.0009). Conclusion. The increased claudin-1 expression in CRC is associated with better prognosis. In addition, claudin-1 was related to the better tumor type and the less venous invasion and lymphatic invasion.

scholarly journals YAP Levels Combined with Plasma CEA Levels Are Prognostic Biomarkers for Early-Clinical-Stage Patients of Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Zihui Xu ◽  
Hui Wang ◽  
Ling Gao ◽  
Hongfeng Zhang ◽  
Xiangyang Wang
Keyword(s):  
Colorectal Cancer ◽  
Lymphatic Metastasis ◽  
Early Stage ◽  
Clinical Stage ◽  
Survival Rates ◽  
Immunohistochemical Analysis ◽  
High Plasma ◽  
Node Ratio ◽  
Early Clinical Stage ◽  
Cancer Tissues

Background. Colorectal cancer (CRC) is one of the most common cancers worldwide. Surgical operation is routinely applied to patients with CRC. An important part of postoperative care for patients is to assess the prognosis of patients, especially those with early-stage cancers. However, effective biomarkers for CRC prognosis remain inadequate. The purpose of this study was to assess the prognostic potential of Yes-associated protein (YAP) and carcinoembryonic antigen (CEA) in early-stage CRC. Methods. A total of 116 matched pairs of CRC tissues and adjacent normal mucosae as well as 73 cases of metastatic lymph nodes were analyzed. Results. The results show that CRC tissues exhibited higher YAP expression compared with the adjacent normal mucosae. Immunohistochemical analysis shows that YAP expression in the CRC or lymphatic metastatic tissues was clearly higher than that in normal mucosae (P<0.01), whereas that in CRC tissues with lymphatic metastasis was higher than that in tissues without lymphatic metastasis (P<0.05). YAP expression is associated with serosal invasion, lymphatic metastasis, lymph node ratio, remote metastasis, Dukes stage, and CEA levels (P<0.05). YAP and CEA are independent predictors of the survival of CRC patients (P<0.05 and P<0.01). YAP predicted CRC prognosis primarily for patients with late-clinical-stage CRC (P=0.002), but not for patients with early-clinical-stage CRC (P=0.083). However, patients with high YAP and high CEA levels exhibited lower overall survival rates than those with low YAP expression in early-clinical-stage CRC (P<0.001). Conclusion. High YAP levels in the cancer tissues combined with high plasma CEA levels are potential biomarkers for predicting CRC prognosis in the early clinical stage.

Identification of epigenetic silencing of GCNT2 expression by comprehensive real-time PCR screening in colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 506-506
Author(s):  
Kazunorii Nakamura ◽  
Horomichi Sawaki ◽  
Keishi Yamashita ◽  
Masahiko Watanabe ◽  
Hisashi Narimatsu
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Real Time ◽  
Cell Lines ◽  
Real Time Pcr ◽  
Critical Role ◽  
Normal Mucosa ◽  
Primary Cancer ◽  
Normal Tissues ◽  
Cancer Tissues

506 Background: Glycoprotein expression profile has been proved to be dramatically altered in human cancers, however specific glycogenes which are aberrant in expression in cancer cells has not been fully identified. Recent accumulated evidence supported notion that the reduced expression of tumor suppressor genes is explained by DNA promoter methylation in human cancer. Methods: We used Comprehensive Real time PCR system (CRPS) for glycogenes (189 genes) to identify genes aberrantly expressed in colorectal cancer tissues (CRC) as compared to the corresponding normal mucosa tissues. GCNT2 was of particular interest among the identified genes in CRC. Results: (1) GCNT2 harbors 3 isoforms which have different promoter regions. (2) All of the 3 isoforms of GCNT2 genes were remarkably decreased in CRC as compared to the corresponding normal mucosa, and each isoform expression was strongly associated with other 2 isoforms in primary cancer tissues by TaqMan real time PCR (R = 0.99-995, p < 0.0001). (3) Among the 5 CRC cell lines (DLD1, HCT116, CACO2, LOVO), those which were silenced in expression were reactivated by demethylating agents such as 5-aza-2’ deoxycytidine and trichostatin A. (4) Promoter region of the variant 2 of GCNT2 was consistent with its silenced expression in CRC cell lines by cloned sequence, so we examined DNA methylation status of the promoter of the GCNT2 variant 2 in 50 primary cancer tissues and the corresponding normal tissues. Quantitative MSP revealed that almost half of normal tissues have methylation as high as tumor tissues, while, in the primary CRC with less methylation in the corresponding normal tissues, DNA methylation was higher in primary CRC tissues than in the corresponding normal tissues. Finally, GCNT2 variant 2 stable transfection induced expression of other 2 isoform variants. Conclusions: We identified novel methylation gene GCNT2 among the glycoenes. Glycoenes that were altered in genomic or epigenetic manner have been few, so GCNT2 may play a critical role in cancer progression through glycan change.

scholarly journals ADAMTS9 is Silenced by Epigenetic Disruption in Colorectal Cancer and Inhibits Cell Growth and Metastasis by Regulating Akt/p53 Signaling

2017 ◽  
Vol 44 (4) ◽  
pp. 1370-1380 ◽  
Author(s):  
Ling Chen ◽  
Jun Tang ◽  
Yixiao Feng ◽  
Shuman Li ◽  
Qin Xiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Promoter Methylation ◽  
Methylation Status ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Matrix Assembly ◽  
Colorectal Cancer Cell Lines ◽  
Cancer Tissues

Background/Aims: ADAMTS (disintegrin-like and metalloproteinase with thrombospondin motifs) proteins are extracellular zinc metalloproteinases that play an important role in extracellular matrix assembly and degradation, connective tissue structuring, angiogenesis, and cell migration. Multiple studies suggest that ADAMTS proteins (e.g. ADAMTS9) can act as tumor suppressors. In gastric, esophageal, and nasopharyngeal carcinomas ADAMTS9 is frequently down-regulated by promoter methylation. Whether ADAMTS9 can function as a tumor suppressor gene (TSG) in colorectal cancer is still unclear. Methods: We performed immunohistochemistry, RT-PCR, and qRT-PCR, to examine the expression of ADAMTS9 in colorectal cancer cell lines and primary colorectal cancer tissues. Methylation-specific PCR was also carried out to investigate the promoter methylation status of ADAMTS9. We also explored the functions of ADAMTS9 in colorectal cancer cell lines through in vitro experiments. Results: ADAMTS9 expression was down-requlated or silenced in 83.3% (5/6) of colorectal cancer cell lines, and frequently repressed in 65.6% (21/32) of colorectal cancer tissues. Down-regulation of ADAMTS9 was partially due to promoter methylation. Exogenous expression of ADAMTS9 in colorectal cancer cell lines inhibited cell proliferation and migration through the regulation of cell cycle and apoptosis. In addition, ADAMTS9 prevented the activation of Akt, and its downstream targets in colorectal cancer cell lines. Conclusion: Our findings suggest ADAMTS9 is a TSG in colorectal cancer.

scholarly journals Anticancer effects of fucoxanthin and fucoxanthinol on colorectal cancer cell lines and colorectal cancer tissues

2015 ◽  
Vol 10 (3) ◽  
pp. 1463-1467 ◽  
Author(s):  
KAZUTO TAKAHASHI ◽  
MASASHI HOSOKAWA ◽  
HIROYUKI KASAJIMA ◽  
KAZUTERU HATANAKA ◽  
KAZUHIRO KUDO ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Anticancer Effects ◽  
Colorectal Cancer Cell Lines ◽  
Cancer Tissues

scholarly journals MicroRNA silencing of CNN1 and CNN2 protein family members regulates biology processes in colorectal cancer by targeting the p53 signal pathway

2020 ◽  
Author(s):  
Fuda Huang ◽  
Mingwei Wei ◽  
Anmin Wang ◽  
Ya Zhang ◽  
Zebang Qin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Expression Levels ◽  
Colon Cancer Cell Lines ◽  
Cancer Tissues

Abstract BackgroundCalponin was first defined as a striated muscle troponin T-like protein that binds actin thin filaments to regulate smooth muscle contraction. There are few studies of CNN1 and CNN2 in colorectal cancer, and the roles these two genes play in colorectal cancer cell lines and the mechanisms by which they act are unknown.MethodsWe used immunohistochemistry to identify expression of the two genes in the cancer tissues. RT-PCR was used to measure expression levels of microRNA. W performed western blots to measure changes in signaling pathways in the context of expression interference.Meanwhile, the same method was used to measure binding relationship between the two genes and key pathway proteins. To determine the relationship between microRNA and gene mRNA, we used the reporter gene method. We used the chi-square and t-test methods to analyze the significance and correlations of the data.Results and conclusionsExpression levels of CNN1 were lower in colon cancer tissues than in normal mucosal tissues. After downregulating CNN1, the cell cycle in colon cancer cell lines progressed quickly, and the expression of related pathway proteins also increased. Expression levels of CNN2 were higher in colon cancer tissues, and its downregulation significantly inhibited cell cycle progression in colon cancer cell lines. We confirmed correlations between the expression of microRNA and CNN2 using data analysis.Bars indicate ± standard errors.*p < 0.05; **p < 0.01 compared with the control. The inhibition of the expression of CNN2 mRNA using microRNA was confirmed using western blot. The combination of the two at the mechanism level was also demonstrated using the reporter gene method.

Effect of JAG2 on migration and invasion in colorectal cancer cell by PRAF2, independent of epithelial-mesenchymal transition.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15107-e15107
Author(s):  
Wan He ◽  
Han Wu ◽  
Dongcheng Liu ◽  
Wenwen Li ◽  
Ruilian Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Lines ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues

e15107 Background: Our previous studies revealed the increased expression of Jagged 2 (JAG2) in most intestinal cancer tissues. In colon cancer cell lines, JAG2 involved in the regulation of migration and invasion without affecting cell proliferation. This study further explored the mechanisms of how JAG2 promotes migration and invasion of colorectal cancer cells. Methods: We analyzed the expression of JAG2 mRNA and protein in normal human colon tissue cells and colorectal cancer cells. The promotive role of JAG2 in migration and invasion was tested by JAG2 siRNA and JAG2 overexpression in various colon cancer cell lines. To understand the mechanisms, we first treated HT29 cells with LY2157299, a TGF-β signaling pathway inhibitor, and Slug siRNA, to identify the cross-talk between JAG2 and EMT pathway. In addition, co-expression status of JAG2 and TGF-β-induced epithelial-mesenchymal transition (EMT) markers was analyzed. Finally, by using siRNA and proteomics technology, co-expressed proteins of JAG2 in colorectal cancer cells were identified. Results: JAG2 was abnormally expressed in colorectal cancer tissues and directly related with clinical stages. Similar to the findings in human tissues, the expression of both JAG2 mRNA and protein was significantly increased in the colorectal cancer cell lines compared with that of normal colorectal cell line CCD18-Co. Interestingly, the promotion of JAG2 in migration and invasion was independent of EMT pathway. Furthermore, we found that the expression of JAG2 was correlated with PRAF2 (PRA1 Domain Family Member 2), a protein involved in the formation of exosome-like vesicles. In the presence of PRAF2, JAG2-rich exosome promoted migration and invasion. JAG2 might regulate the migration and invasion of colon cell through PRAF2. Conclusions: This is the evidence supporting the biological function of JAG2 in migration and invasion through non-EMT-dependent pathways and also the first exploration of the role of PRAF2 in colorectal cancer cells. These findings provide the theoretical basis for potential targeted therapy against JAG2/PRAF2.

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