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

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
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.

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

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.

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

2020 ◽  
pp. 1-9
Author(s):  
Guangyao Li ◽  
Zhengjun Zhang ◽  
Guochao Ge ◽  
Ke Fang ◽  
Jianyu Zhu
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Tumor Development ◽  
Normal Mucosa ◽  
Clinical Analysis ◽  
Immunoglobulin Superfamily ◽  
Node Metastasis ◽  
Adjacent Normal Mucosa ◽  
Potential Biomarker

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.

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

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.

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

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

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

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.

16. Apical lymph node metastasis and survival in resected colorectal cancer

Pathology ◽  
2015 ◽  
Vol 47 ◽  
pp. S105
Author(s):  
Nav Gill ◽  
Christopher W. Toon ◽  
Nicole Watson ◽  
Anthony J. Gill
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Node Metastasis

Tumor Budding and Pathological Differentiation Are Predictive Markers for Lymph Node Metastasis in T1 Colorectal Cancer

2006 ◽  
Vol 63 (5) ◽  
pp. AB216 ◽  
Author(s):  
Hitoshi Yamauchi ◽  
Kazutomo Togashi ◽  
Hiroshi Kawamura ◽  
Junichi Sasaki ◽  
Masaki Okada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Predictive Markers ◽  
Tumor Budding ◽  
Node Metastasis ◽  
Pathological Differentiation ◽  
T1 Colorectal Cancer

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 Identification of lymph node metastasis-related microRNAs in lung adenocarcinoma and analysis of the underlying mechanisms using a bioinformatics approach

2016 ◽  
Vol 242 (7) ◽  
pp. 709-717 ◽  
Author(s):  
Li Yan ◽  
Demin Jiao ◽  
Huizhen Hu ◽  
Jian Wang ◽  
Xiali Tang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lung Adenocarcinoma ◽  
Lymphatic Metastasis ◽  
Target Genes ◽  
Bioinformatics Analyses ◽  
Node Metastasis ◽  
Primary Lung Adenocarcinoma ◽  
Underlying Mechanisms

This study aimed to screen lymphatic metastasis-related microRNAs (miRNAs) in lung adenocarcinoma and explore their underlying mechanisms using bioinformatics. The miRNA expression in primary lung adenocarcinoma, matched adjacent non-tumorigenic and lymph node metastasis tissues of patients were profiled via microarray. The screened metastasis-related miRNAs were then validated using quantitative real-time PCR in a second cohort of lung adenocarcinoma patients with lymphatic metastasis. Significance was determined using a paired t-test. Target genes of the metastasis-related miRNAs were predicted using TargetScan, and transcription factors (TFs) were predicted based on the TRANSFAC and ENCODE databases. Furthermore, the related long non-coding RNAs (lncRNAs) were screened with starBase v2.0. The miRNA-TF-mRNA and lncRNA-miRNA-mRNA networks were constructed to determine the key interactions associated with lung adenocarcinoma metastasis. According to the miRNA microarray results, there were 10 miRNAs that were differentially expressed in metastatic tissues compared with primary tumor and adjacent non-tumorigenic tissues. Among them were increased levels of miR-146a-5p, miR-342-3p, and miR-150-5p, which were validated in the second cohort. Based on the miRNA-TF-mRNA network, vascular endothelial growth factor A and transcription factors (TFs) including TP53, SMAD4, and EP300 were recognized as critical targets of the three miRNAs. Interactions involving SNHG16–miR-146a-5p–SMAD4 and RP6-24A23.7–miR-342-3p/miR-150-5p–EP300 were highlighted according to the lncRNA-miRNA-mRNA network. miR-146a-5p, miR-342-3p, and miR-150-5p are lymphatic metastasis-related miRNAs in lung adenocarcinoma. Bioinformatics analyses demonstrated that SNHG16 might inhibit the interaction between miR-146a-5p and SMAD4, while RP6-24A23.7 might weaken miR-342-3p–EP300 and miR-150-5p–EP300 interactions in metastasis.

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