Upregulated CNTN1 is associated with lymph node metastasis and poor prognosis of colorectal cancer

BACKGROUND: Contactin1 (CNTN1), a member of the immunoglobulin superfamily, is known to correlate with tumor development and progression. Although recent studies have found that elevated CNTN1 has been demonstrated in some types of cancers, the expression and prognosis of CNTN1 in colorectal cancer (CRC) are unclear. Here, we aimed to determine the clinicopathological characteristics and prognostic role of CNTN1 in CRC patients. METHODS: The protein expression of CNTN1 in tumor tissues was evaluated by immunohistochemistry. In addition, the mRNA and protein expressions of CNTN1 were examined by qRT-PCR and Western blotting analysis in 40 matched adjacent normal mucosa samples. The relationships of CNTN1 with clinicopathological data and prognosis significance were analyzed. RESULTS: Immunohistochemical consequence suggested that the protein level of CNTN1 was obviously raised in CRC compared with adjacent normal mucosa tissues (56.9% vs 10.3%, P< 0.05). In addition, we detected a significant increase in CNTN1 mRNA and protein levels in CRC tissues compared with the matched adjacent normal mucosa tissues. Moreover, increased CNTN1 exprssion was significantly associated with tumor size, lymph node metastasis (LNM), tumor node-metastasis (TNM) stage and carcino-embryonic antigen (CEA) in clinical analysis. Kaplan-Meier analysis suggested that patients with CNTN1 over-expression showed worse overall survival (OS) (P= 0.001). Multivariate analysis indicated that high CNTN1 expression was an independent predictor for poor OS in CRC patients (P= 0.028). Further analysis revealed that patients with high CNTN1 combined with LNM present accurately predicted poorer outcome. CONCLUSION: Taken together, the findingsindicate that CNTN1 plays a significant role and serve as a potential biomarker for the prediction of adverse prognosis in CRC. Intriguingly, high express of CNTN1 + LNM-present combination may improve the accuracy of prognosis.

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Proteomic analysis shows down-regulations of cytoplasmic carbonic anhydrases, CAI and CAII, are early events of colorectal carcinogenesis but are not correlated with lymph node metastasis

Tumori Journal ◽

10.1177/030089161209800617 ◽

2012 ◽

Vol 98 (6) ◽

pp. 783-791 ◽

Cited By ~ 4

Author(s):

Ning Wang ◽

Yang Chen ◽

Yuchen Han ◽

Yue Zhao ◽

Yu Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Cancer Progression ◽

Normal Mucosa ◽

Laser Desorption Ionization ◽

Ionization Time ◽

Node Metastasis ◽

Flight Mass Spectrometry ◽

Differential Gel Electrophoresis

Aim The aim of the study was to screen the markedly down-regulated proteins in colorectal cancer and analyze their relationship to carcinogenesis, cancer progression and pathological aspects. Methods Proteomic analysis was preformed on six fresh colorectal cancer tissues and paired normal colorectal mucosa by two-dimensional differential gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Two markedly down-regulated proteins among the proteins, of which the expressions were significantly decreased in colorectal cancer compared to normal mucosa, were confirmed by Western Blot in 12 colorectal cancers. Their relationship to carcinogenesis, cancer progression and pathological aspects of colorectal cancer were analyzed in 64 colorectal cancer and paired normal mucosa, 27 benign polyps, and 20 lymph node metastases by immunohistochemistry. Results Two-dimensional differential gel electrophoresis analysis showed there were 2 protein spots, of which the average abundances decreased 3.62 and 3.76 fold in colorectal cancer compared to normal mucosa, respectively. They were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry as carbonic anhydrase I and II (CAI and CAII). Validation by Western Blot in 12 colorectal cancers showed there were significantly different expressions of CAI and CAII between colorectal cancer and normal mucosa (P = 0.002 and 0.027, respectively). Immunohistochemistry analysis indicated the expression of CAI and CAII was decreased from normal mucosa to benign polyps, and to colorectal cancer stepwise significantly (P <0.05). However, there were no differences in their expressions between lymph node metastasis and colorectal cancer (P >0.05). There were decreasing trends of CAI and CAII expressions from well to poor differentiation and from stage I or II to stage III or IV, but they were not statistically significant (P >0.05). Conclusions CAI and CAII are necessary enzymes of the colorectum for their normal function. Down-regulations of CAI and CAII are early events of colorectum carcinogenesis. They have no correlations with lymph node metastasis.

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Significance of Glutathione Peroxidase 1 and Caudal-Related Homeodomain Transcription Factor in Human Gastric Adenocarcinoma

Gastroenterology Research and Practice ◽

10.1155/2013/380193 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Jing Jing Han ◽

De Rong Xie ◽

Li Li Wang ◽

Ye Qing Liu ◽

Gong Fa Wu ◽

...

Keyword(s):

Transcription Factor ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Glutathione Peroxidase ◽

Normal Mucosa ◽

Clinicopathological Features ◽

Glutathione Peroxidase 1 ◽

Node Metastasis ◽

Adjacent Normal Mucosa ◽

Extensive Lymph Node

Aim. To investigate the expressions of glutathione peroxidase 1 (GPX1) and caudal-related homeodomain transcription factor (CDX2) in GAC and their correlation with clinicopathological features and tumor cell proliferation.Methods. The expressions of GPX1, CDX2, and Ki67 were immunohistochemically evaluated in 172 GAC specimens. The association of GPX1 and CDX2 with patient’s clinicopathological features and Ki67 positive rate was analyzed statistically.Results. In 172 cases of GAC, the expression of GPX1 was weaker than that in adjacent normal mucosa, and the expression of CDX2 was higher than that in adjacent normal mucosa. High expression GPX1 strong-expression was associated with differentiation, Lauren type, WHO type and extensive lymph node metastasis of GAC. High expression of CDX2 was associated with differentiation, Lauren type, WHO type, extensive lymph node metastasis, and TNM of GAC. Survival curves showed that expressions of GPX1 and CDX2 were factors of good outcome ( and .02, resp.). According to multivariate analysis, only lymph node metastasis, TNM stage, and CDX2 expression were independently associated with survival. In addition, a strong association of GPX1 expression was noted with Ki67 and CDX2.Conclusions. The expression of GPX1 and CDX2 may play a role in the carcinogenesis, differentiation, and progression of GAC, and CDX2 may be an independent prognostic factor.

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Over-expression of Nav1.6 channels is associated with lymph node metastases in colorectal cancer

World Journal of Surgical Oncology ◽

10.1186/s12957-019-1715-4 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Shuiquan Lin ◽

Yangbo Lv ◽

Jianguang Xu ◽

Xinglong Mao ◽

Zhenhong Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Lymph Nodes ◽

Chemokine Receptors ◽

Tumor Development ◽

Node Metastasis ◽

Key Factor ◽

Nav Channels ◽

The One

Abstract Background and objectives Lymph node metastasis is a key factor in predicting and determining the prognosis of patients with colorectal cancer (CRC). Sodium channels are highly expressed in a variety of tumors and are closely related to tumor development, metastasis, and invasion. We investigated the relationship between the expressions of different subtypes of Nav channels and lymph node metastasis of CRC. Methods Real-time PCR (RT-qPCR) was carried out to measure the expressions of different sodium channel subtypes, chemokine receptors (CCR2, CCR4, CCR7), and lymphocyte infiltration-related biomarkers (CD3e, CD8a, IL-2RA) in CRC tissues from 97 patients. The expressions of Nav1.5 and Nav1.6 in surgically isolated lymph nodes were detected by immunohistochemistry. Correlation analysis between expressions of different genes and lymph node metastasis was performed by two-tailed t test. Results Nav1.1 and Nav1.6 were highly expressed in CRC tissues and positively correlated with CRC lymph node metastasis. Nav1.6 was also highly expressed in metastatic lymph nodes. Further analysis showed that the high expression of Nav1.6 was closely related to the one of CCR2\CCR4 in tumor lymph node metastasis. Conclusions These results suggested that Nav1.6 might be a novel marker for CRC lymph node metastasis.

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Identification of the miRNA signature and key genes in colorectal cancer lymph node metastasis

Cancer Cell International ◽

10.1186/s12935-021-02058-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xi Wang ◽

Guangyu Gao ◽

Zhengrong Chen ◽

Zhihao Chen ◽

Mingxiao Han ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Expression Profiles ◽

Bioinformatic Analysis ◽

The Cancer Genome Atlas ◽

Node Metastasis ◽

Novel Mirna ◽

Potential Biomarker

Abstract Background Because its metastasis to the lymph nodes are closely related to poor prognosis, miRNAs and mRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of colorectal cancer (CRC). This study aimed to identify novel gene signatures in the lymph node metastasis of CRC. Methods GSE56350, GSE70574, and GSE95109 datasets were downloaded from the Gene Expression Omnibus (GEO) database, while data from 569 colorectal cancer cases were also downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DE-miRNAs) were calculated using R programming language (Version 3.6.3), while gene ontology and enrichment analysis of target mRNAs were performed using FunRich (http://www.funrich.org). Furthermore, the mRNA–miRNA network was constructed using Cytoscape software (Version 3.8.0). Gene expression levels were verified using the GEO datasets. Similarly, quantitative real-time PCR (qPCR) was used to examine expression profiles from 20 paired non-metastatic and metastatic lymph node tissue samples obtained from patients with CRC. Results In total, five DE-miRNAs were selected, and 34 mRNAs were identified after filtering the results. Moreover, two key miRNAs (hsa-miR-99a, hsa-miR-100) and one gene (heparan sulfate-glucosamine 3-sulfotransferase 2 [HS3ST2]) were identified. The GEO datasets analysis and qPCR results showed that the expression of key miRNA and genes were consistent with that obtained from the bioinformatic analysis. A novel miRNA–mRNA network capable of predicting the prognosis and confirmed experimentally, hsa-miR-99a-HS3ST2-hsa-miR-100, was found after expression analysis in metastasized lymph node tissue from CRC samples. Conclusion In summary, miRNAs and genes with potential as biomarkers were found and a novel miRNA–mRNA network was established for CRC lymph node metastasis by systematic bioinformatic analysis and experimental validation. This network may be used as a potential biomarker in the development of lymph node metastatic CRC.

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Diagnostic Value Investigation and Bioinformatics Analysis of miR-31 in Patients with Lymph Node Metastasis of Colorectal Cancer

Analytical Cellular Pathology ◽

10.1155/2019/9740475 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Wu-wen Zhang ◽

Xin-liang Ming ◽

Yuan Rong ◽

Chao-qun Huang ◽

Hong Weng ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Target Genes ◽

Bioinformatics Analysis ◽

Wnt Signaling Pathway ◽

Developed Countries ◽

Diagnostic Biomarkers ◽

Node Metastasis ◽

Potential Biomarker

Colorectal cancer (CRC) is one of the most frequent cancers occurring in developed countries. Distant CRC metastasis causes more than 90% of CRC-associated mortality. MicroRNAs (miRNAs) play a key role in regulating tumor metastasis and could be potential diagnostic biomarkers in CRC patients. This study is aimed at identifying miRNAs that can be used as diagnostic biomarkers for CRC metastasis. Towards this goal, we compared the expression of five miRNAs commonly associated with metastasis (i.e., miR-10b, miR-200c, miR-155, miR-21, and miR-31) between primary CRC (pCRC) tissues and corresponding metastatic lymph nodes (mCRC). Further, bioinformatics analysis of miR-31 was performed to predict target genes and related signaling pathways. Results showed that miR-31, miR-21, miR-10b, and miR-155 expression was increased to different extents, while miR-200c expression was lower in mCRC than that in pCRC. Moreover, we found that the level of both miR-31 and miR-21 was notably increased in pCRC when lymph node metastasis (LNM) was present, and the increase of miR-31 expression was more profound. Hence, upregulated miR-31 and miR-21 expression might be a miRNA signature in CRC metastasis. Moreover, we detected a higher miR-31 level in the plasma of CRC patients with LNM compared to patients without LNM or healthy individuals. With the bioinformatics analysis of miR-31, 121 putative target genes and transition of mitotic cell cycle and Wnt signaling pathway were identified to possibly play a role in CRC progression. We next identified seven hub genes via module analysis; of these, TNS1 was most likely to be the target of miR-31 and had significant prognostic value for CRC patients. In conclusion, miR-31 is significantly increased in the cancer tissues and plasma of CRC patients with LNM; thus, a high level of miR-31 in the plasma is a potential biomarker for the diagnosis of LNM of CRC.

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RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.555 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 555-555

Author(s):

Hiroki Imaoka ◽

Yuji Toiyama ◽

Susumu Saigusa ◽

Koichiro Mori ◽

Tomofumi Noguchi ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Protein Expression ◽

Clinical Significance ◽

Poor Prognosis ◽

Cellular Proliferation ◽

Migration And Invasion ◽

Node Metastasis ◽

Potential Biomarker

555 Background: Rac GTPase activating protein (RacGAP) 1 plays a key role in controlling various cellular phenomena including cytokinesis, transformation and migration. Recently, the clinical significance of RacGAP1 expression has been reported in several malignancies. However, direct association between the RacGAP1 expression and colorectal cancer (CRC) has not been fully investigated. The aim of this study is to elucidate the function and clinical significance of RacGAP1 expression in CRC. Methods: The intrinsic functions of RacGAP1 in CRC cells were analyzed using small interfering RNA (siRNA). We analyzed RacGAP1 mRNA expression in surgical specimens from 193 CRC patients (Cohort 1) by real-time polymerase chain reaction. Then, we validated RacGAP1 protein expression using formalin-fixed paraffin-embedded samples from 298 CRC patients (Cohort 2) by immunohistochemistry. Finally, we evaluated the association between RacGAP1 mRNA and protein expression and clinicopathological data. Results: Reduced RacGAP1 expression by siRNA in CRC cell lines showed significantly decreased cellular proliferation, migration, and invasion. In Cohort 1, RacGAP1 expression in CRC was significantly higher than in adjacent normal mucosa, and increased according to TNM stage progression. High RacGAP1 expression in tumors was significantly associated with progression and prognosis. In Cohort 2, RacGAP1 protein was overexpressed mainly in the nuclei of CRC cells; however, its expression was scarcely observed in normal colorectal mucosa. RacGAP1 protein expression was significantly higher in CRC patients with higher T stage, vessel invasion, and lymph node and distant metastasis. Increased expression of RacGAP1 protein was significantly associated with poor disease-free and overall survival. Multivariate analyses revealed that high RacGAP1 expression was an independent predictive marker for lymph node metastasis, recurrence, and poor prognosis in CRC. Conclusions: Our data provide novel evidence for the biological and clinical significance of RacGAP1 as a potential biomarker for identifying patients with lymph node metastasis and poor prognosis in CRC.

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Microenvironmental markers are correlated with lymph node metastasis in invasive submucosal colorectal cancer

Histopathology ◽

10.1111/his.14388 ◽

2021 ◽

Author(s):

Tamotsu Sugai ◽

Noriyuki Yamada ◽

Mitsumasa Osakabe ◽

Mai Hashimoto ◽

Noriyuki Uesugi ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Node Metastasis ◽

Submucosal Colorectal Cancer

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Increased Expression of VANGL1 is Predictive of Lymph Node Metastasis in Colorectal Cancer: Results from a 20-Gene Expression Signature

Journal of Personalized Medicine ◽

10.3390/jpm11020126 ◽

2021 ◽

Vol 11 (2) ◽

pp. 126

Author(s):

Noshad Peyravian ◽

Stefania Nobili ◽

Zahra Pezeshkian ◽

Meysam Olfatifar ◽

Afshin Moradi ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Candidate Genes ◽

Case Series ◽

Gene Expression Signature ◽

Gene Panel ◽

Expression Levels ◽

Node Metastasis

This study aimed at building a prognostic signature based on a candidate gene panel whose expression may be associated with lymph node metastasis (LNM), thus potentially able to predict colorectal cancer (CRC) progression and patient survival. The mRNA expression levels of 20 candidate genes were evaluated by RT-qPCR in cancer and normal mucosa formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients. Receiver operating characteristic curves were used to evaluate the prognosis performance of our model by calculating the area under the curve (AUC) values corresponding to stage and metastasis. A total of 100 FFPE primary tumor tissues from stage I–IV CRC patients were collected and analyzed. Among the 20 candidate genes we studied, only the expression levels of VANGL1 significantly varied between patients with and without LNMs (p = 0.02). Additionally, the AUC value of the 20-gene panel was found to have the highest predictive performance (i.e., AUC = 79.84%) for LNMs compared with that of two subpanels including 5 and 10 genes. According to our results, VANGL1 gene expression levels are able to estimate LNMs in different stages of CRC. After a proper validation in a wider case series, the evaluation of VANGL1 gene expression and that of the 20-gene panel signature could help in the future in the prediction of CRC progression.

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