scholarly journals Follistatin-Like 3 Correlates With Lymph Node Metastasis and Serves as a Biomarker of Extracellular Matrix Remodeling in Colorectal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Chao Yang ◽  
Fengyu Cao ◽  
Shuoyang Huang ◽  
Yongbin Zheng
Keyword(s):  
Colorectal Cancer ◽  
Extracellular Matrix ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Protein Level ◽  
Cox Regression ◽  
External Validation ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Node Metastasis

BackgroundAs a heterogeneous disease, colorectal cancer (CRC) presents a great challenge to individualized treatment due to its lymph node metastasis (LNM). Existing studies have shown that immune and stromal components in extracellular matrix (ECM) act as important part in tumorigenicity and progression, while their roles in LNM have not been fully elucidated. Here, crucial ECM-related genes responsible for LNM in CRC were selected by multi-omics analysis.MethodsFirstly, we characterized the immune infiltration landscape of CRC samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases by using ssGSEA algorithm. The CRC patients were divided into several immune subgroups by hierarchical clustering analyses. Then, differential genes were identified among immune subgroups and CRC vs. normal tissues in TCGA and GEO GSE39582 cohorts, respectively. Next, weighted correlation network analysis (WGCNA) was employed to construct a co-expression network to find LNM-related modules and hub genes. Subsequently, we evaluated the clinical value of hub gene in prognostic prediction and chemotherapy/immunotherapy. Besides, the protein level of key gene was verified in an external cohort from our center. Finally, we explored the underlying mechanism of FSTL3-mediated LNM by Gene function annotation and correlation analysis.ResultsTwo immune subgroups, namely Immunity_High and Immunity_Low, were defined among the two CRC cohorts using ssGSEA algorithm, respectively. Based on the two immune subgroups, 2,635 overlapping differentially expressed genes were obtained from two cohorts, which were sequentially subjected to WGCNA and univariate Cox regression analysis. Ultimately, FSTL3 was selected as the key gene. Here, we first confirmed that overexpression of FSTL3 correlated with LNM and worse prognosis in CRC and was verified at the protein level in the external validation cohort. Moreover, FSTL3 expression showed strongly positive correlation with immune and stromal components in ECM. We furthermore found that FSTL3 may accelerate LNM through the formation of inhibitory immune microenvironment via promoting macrophage and fibroblast polarization and T cell exhaustion. Interestingly, high FSTL3 expression is linked to chemoresistance, but immunotherapy-sensitive.ConclusionFSTL3 is identified as a biomarker for ECM remodeling and worse clinical outcomes for the first time in CRC and is also a potential immunotherapeutic target to block LNM for CRC.

scholarly journals Serum exosomal miR-4787-3p as potential lymph node metastasis and prognostic marker in esophageal squamous cell carcinoma.

2021 ◽  
Author(s):  
Shuang Liu ◽  
Zheng Lin ◽  
Jianwen Wang ◽  
Zerong Zheng ◽  
Wenqing Rao ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cox Regression ◽  
High Serum ◽  
Migration And Invasion ◽  
Cox Regression Analysis ◽  
Mirna Array ◽  
Node Metastasis

Abstract Background: To explore the miR-4787-3p expression levels in the serum exosome and tissue and its role in lymph node metastasis and prognosis in ESCC. Methods: The miRNA array was conducted to detect the ESCC serum exosomal miRNAs expression. A receiver operating characteristic (ROC) curve was constructed to determine the predictive ESCC with lymph node metastasis efficacy of serum exosomal miR-4784-3p. The Cox regression analysis was preformed to explore prognostic factors for ESCC. Transwell assay and CCK-8 assays were utilized to evaluate cell migration, invasion, and proliferation, respectively. Results: High serum exosomal miR-4787-3p expression was demonstrated in lymph node metastasis group (P =0.011). The serum exosomal miR-4787-3p expression was significantly associated with histologic grade (P = 0.010), and TNM stage (P = 0.033). However, there was no significant relationship between tissue miR-4787-3p expression and clinical characteristics (P >0.05). ROC analyses revealed that the AUCs of serum exosomal miR-4787-3p for lymph node metastasis prediction was 0.787. The Cox regression analysis found that high expression serum exosomal miR-4787-3p were correlated with poor prognoses (for OS, HR=2.68, 95% CI: 1.02~7.04; for DFS, HR = 2.65, 95% CI: 1.05~6.68). Nevertheless, no association between tissue miR-4787-3p expression and ESCC prognosis. In addition, upregulated expression of miR-4787-3p could promote migration and invasion in vitro. Conclusions: Serum exosomal miR-4787-3p can be promising biomarkers for ESCC metastasis and prognosis

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.

scholarly journals Prognosis analysis of patients with resectable T4 colorectal cancer

2020 ◽  
Author(s):  
Wei Chen ◽  
Jun-Wen Ye ◽  
Xiao-ping Tan ◽  
Yan Zhang ◽  
Jing-Lin Liang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Patients ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Independent Factor ◽  
Node Metastasis ◽  
Colorectal Cancer Patients

Abstract Objective: To observe the factors related to survival and prognosis of patients with resectable stage T4 colorectal cancer. Methods : 148 patients with resectable stage T4 colorectal cancer who underwent surgery in the first Affiliated Hospital of Sun Yat-sen University between August, 1994 and December, 2005 were retrospectively analyzed. Univariate and multivariate analyses of associations between clinicopathological variables and survival were analyzed using the Cox regression model. Results: At the end of December of 2010 or death, the 5-year and 10 years OS rates were 49.0% and 32.2% respectively, the median OS was 25 months. The disease free survival rates (DFS) at 5 and 10 years were 44.2% and 30.3% respectively. In univariate analysis, patients with postoperative pathology lymph node metastasis was associated with the prognosis of patients with OS (all P< 0.01), postoperative adjuvant therapy failed to improve OS and DFS (P>0.05). Postoperative pathology lymph node metastasis was associated with DFS too (all P< 0.01). In multivariate analysis, postoperative pathology lymph node metastasis was independent factor affected OS and DFS in colorectal cancer patients. Conclusion: Postoperative prognosis of T4 colorectal cancer patients is poor, postoperative pathology lymph node positive was an independent factor affect OS and DFS.

scholarly journals Identification of Mirna Signature and Key Genes in Colorectal Cancer Lymph Node Metastasis

2021 ◽  
Author(s):  
Xi Wang ◽  
Guangyu Gao ◽  
Zhengrong Chen ◽  
Zhihao Chen ◽  
Mingxiao Han ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cancer Statistics ◽  
Node Metastasis ◽  
Novel Mirna

Abstract Background: miRNAs and mRNAs can serve as biomarkers for the diagnosis, prognosis and therapy of colorectal cancer (CRC), whose metastasis to lymph node is closely related to the poor prognosis. The current study aimed to identify the novel gene signatures in the lymph node metastasis of CRC.Methods: GSE56350, GSE70574 and GSE95109 were downloaded from the Gene Expression Omnibus (GEO) database and 569 colorectal cancer statistics were also downloaded from the The Cancer Genome Atlas (TCGA) database. Differentially expressed miRNAs (DE-miRNAs) were calculated by using R software. Besides, gene ontology and Enriched pathway analysis of target mRNAs were analyzed by using FunRich. Furthermore, the mRNA-miRNA network was constructed using Cytoscape software. Gene expression level was verified by GEO datasets and forty paired lymph node non-metastasis CRC tissues and lymph node metastatic CRC tissues obtained from patients with CRC using quantitative real-time PCR (qPCR) .Results: In total, five DE-miRNAs were selected, and 34 mRNAs were identified after filtering. Moreover, 2 key miRNAs and one gene were identified including hsa-miR-99a, has-miR-100 and heparan sulfate-glucosamine 3-sulfotransferase 2 (HS3ST2). The GEO datasets analysis and qPCR results showed the expression of key miRNA and genes were consistent with that in the bioinformatic analysis. A novel miRNA-mRNA network, hsa-miR-99a-HS3ST2-has-miR-100 was found in lymph node metastasis of CRC after expression analysis, prognostic prediction and experiments confirmation.Conclusions: In summary, the potential miRNAs and genes were found and a novel miRNA-mRNA network was established in CRC lymph node metastasis by systematic bioinformatic analysis and experiments validation, which may be used as potential biomarkers in the development of lymph node metastatic CRC.

CD133 status influences in prognosis of patients with metastatic colorectal cancer receiving cetuximab.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 509-509 ◽  
Author(s):  
Dai Inoue ◽  
Satoshi Matsusaka ◽  
Noriko Yamamoto ◽  
Mitsukuni Suenaga ◽  
Yuji Mishima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Lymph Node Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Lung Metastasis ◽  
Peritoneal Metastasis ◽  
Chimeric Mouse ◽  
Cox Regression Analysis ◽  
Node Metastasis

509 Background: Recently, the cancer stem cell (CSC) theory has been proposed, and CD133 has been suggested as a potential marker of CSCs in metastatic colorectal cancer (mCRC). Cetuximab, an IgG1 anti-EGFR chimeric mouse/human monoclonal antibody, has been approved for the treatment of mCRC. The purpose of this study is to evaluate the prognostic significance of CD133 expression in mCRC treated with cetuximab in combination with chemotherapy. Methods: We evaluated the prognosis of pts with mCRC treated with cetuximab retrospectively, and performed immunohistochemical staining to analyze the CD133 status. Non-parametric statistics, univariate and multivariate analysis were used. Results: From October 2008 to June 2009, 56 pts with measurable metastatic colorectal cancer were received cetuximab and 43 were evaluable. Patients characteristics were as follows : median age : 59.6 years (range 28-80) , PS 0/1 : 30/13 , colon/rectum : 28/15 , metastatic site (liver +/- : 35/8 , lung +/- : 32/11 , bone +/- : 6/37 , peritoneum +/- : 6/37 , lymph node +/- : 11/32 , local +/- : 3/40), best response rate was 9.3% (CR/PR/SD/PD : 1/3/19/11). Compared with CD133- pts with colorectal cancer , the progression-free survival (PFS) of CD133+ pts was significantly better (5.5 month; 95% CI, 4.4-6.7,p=0.026), and median overall survival (OS) was also significantly better (11.0 month; 95% CI, 5.4-16.5, p=0.002). In univariate analysis, liver metastasis, lung metastasis, peritoneal metastasis, lymph node metastasis, age, and CD133 at the baseline predicted PFS, and age, gender, liver metastasis, lung metastasis, bone metastasis, peritoneal metastasis, lymph node metastasis at the baseline, the presence of skin rash, and CD133 predicted OS. In order to evaluate the independent predictive effect of chemotherapy, multivariate Cox regression analysis was carried out. It showed that CD133 was the strongest predictor. Conclusions: CD133 status at the baseline was correlated with the prognosis of patients treated with cetuximab, suggesting that CD133 status might play a role to estimate the prognosis.

scholarly journals Landscape of Genome-Wide DNA Methylation of Colorectal Cancer Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2710
Author(s):  
Carmen Ili ◽  
Kurt Buchegger ◽  
Hannah Demond ◽  
Juan Castillo-Fernandez ◽  
Gavin Kelsey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Cpg Island ◽  
The Cancer Genome Atlas ◽  
Node Metastasis ◽  
Genome Wide

Colorectal cancer is a heterogeneous disease caused by both genetic and epigenetics factors. Analysing DNA methylation changes occurring during colorectal cancer progression and metastasis formation is crucial for the identification of novel epigenetic markers of patient prognosis. Genome-wide methylation sequencing of paired samples of colon (normal adjacent, primary tumour and lymph node metastasis) showed global hypomethylation and CpG island (CGI) hypermethylation of primary tumours compared to normal. In metastasis we observed high global and non-CGI regions methylation, but lower CGI methylation, compared to primary tumours. Gene ontology analysis showed shared biological processes between hypermethylated CGIs in metastasis and primary tumours. After complementary analysis with The Cancer Genome Atlas (TCGA) cohort, FIGN, HTRA3, BDNF, HCN4 and STAC2 genes were found associated with poor survival. We mapped the methylation landscape of colon normal tissues, primary tumours and lymph node metastasis, being capable of identified methylation changes throughout the genome. Furthermore, we found five genes with potential for methylation biomarkers of poor prognosis in colorectal cancer patients.

scholarly journals eIF4E Overexpression Is Associated with Poor Prognoses of Ovarian Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Jun Zheng ◽  
Xueqing Li ◽  
Chunyan Zhang ◽  
Yiqiang Zhang
Keyword(s):  
Ovarian Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cyclin D1 ◽  
Cox Regression ◽  
Cancer Tissue ◽  
Tissue Samples ◽  
Cox Regression Analysis ◽  
Node Metastasis ◽  
Incidence And Mortality

Aim. Ovarian cancer is a common malignant tumor of the gynecological oncology worldwide, with a high incidence and mortality rate and poor prognosis. Searching for new diagnostic molecular biomarkers for ovarian cancer is extremely significant. Methods. Here, we analyzed the expression rates of eIF4E and cyclin D1 proteins in 123 cases of cancer tissue samples and 38 cases of paracancerous tissue samples and studied the connection between the expression rates of eIF4E and cyclin D1 proteins by immunohistochemistry and statistically correlated with clinicopathological features in ovarian cancer. Results. The results showed that the expression rates of eIF4E and cyclin D1 proteins in ovarian cancer tissues were significantly higher than those in noncancerous epithelial ovarian tissues ( P = 0.001 and P = 0.032 , respectively). Additionally, the results revealed that a higher expression rate of eIF4E ( P = 0.008 ) was found in the advanced stage (stage III/IV), and also patients with cervical lymph node metastasis displayed higher expression of eIF4E ( P < 0.001 ) and cyclin D1 ( P = 0.033 ) than those without lymph node metastasis. Spearman’s rank correlation test showed that there was a significant positive correlation between the eIF4E and cyclin D1 proteins in ovarian cancer. The Kaplan-Meier method showed that patients with lower expression of eIF4E had marginally better survival than those with high expression of eIF4E ( P = 0.012 ). Multivariate Cox regression analysis further identified that positive expression of eIF4E was an independent prognostic factor. Conclusion. In ovarian cancer, eIF4E might be a valuable biomarker to predict poor prognoses and a potential therapeutic target to develop valid treatment strategies.

scholarly journals Development and Validation of Prognostic Nomogram for Primary Peritoneal Serous Carcinoma Compared With FIGO Staging System: A Population-Based Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Ming Chen ◽  
Zhenzhen Wen ◽  
Zhengwei Qi ◽  
Min Gao
Keyword(s):  
Prognostic Factors ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cox Regression ◽  
Staging System ◽  
Serous Carcinoma ◽  
Cox Regression Analysis ◽  
Node Metastasis ◽  
Figo Staging ◽  
Gynecology And Obstetrics

BackgroundPrimary peritoneal serous carcinoma (PPSC) is a rare tumor that lacks a prognostic prediction model. Our study aims to develop a nomogram to predict overall survival (OS) of PPSC patients.MethodsPatients confirmed to have PPSC between 2004 and 2012 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. LASSO and multivariate Cox regression analyses were used to screen for meaningful independent prognostic factors to construct a nomogram model for 3-, 5-, and 10-year OS among patients with PPSC. The nomogram compared the discrimination, calibration, and net benefits with the International Federation of Gynecology and Obstetrics (FIGO) staging system of PPSC patients.ResultsEight variables were selected to establish the nomogram for PPSC. The established nomogram performed significantly better than the FIGO staging system (p &lt; 0.05). The 3-, 5-, and 10-year OS of PPSC was 0.498, 0.306, and 0.152, respectively. Patients of old age, widowed marital status, grade high, FIGO IIIB, IIIC, or IV, lymph node metastasis, no lymphadenectomy, no surgery, and no chemotherapy got higher score which corresponds with higher risk and lower OS. In the multivariate Cox regression analysis, age, histological grade, FIGO staging, lymph node metastasis, and lymphadenectomy (four or more) were identified as independent prognostic factors for PPSC.ConclusionsPPSC patients have distinct characteristics with respect to their presentation and survival outcomes. A prognostic nomogram constructed by various clinical indicators can provide better and more accurate predictions for patients with PPSC.

scholarly journals Nomogram Development and External Validation for Predicting the Risk of Lymph Node Metastasis in T1 Colorectal Cancer

2019 ◽  
Vol 51 (4) ◽  
pp. 1275-1284 ◽  
Author(s):  
Jung Ryul Oh ◽  
Boram Park ◽  
Seongdae Lee ◽  
Kyung Su Han ◽  
Eui-Gon Youk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
External Validation ◽  
Node Metastasis ◽  
T1 Colorectal Cancer

Development and validation of a six-gene signature for predicting prognosis in prostate cancer patients with lymph node metastasis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17524-e17524
Author(s):  
Jinan Guo ◽  
Wenzhuan Xie ◽  
Mengli Huang ◽  
Chan Gao
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Lymph Node Metastasis ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Wild Type ◽  
Cox Regression Analysis ◽  
Node Metastasis

e17524 Background: Prostate cancer (PCa) patients with lymph node metastasis (LNM) always exhibit poor clinical outcomes. A gene signature that could predict survival in these patients would allow for earlier detection of mortality risk and will also guide individualized therapy. Methods: A prediction model was developed using a public cohort consisting of 623 patients with clinicopathologically confirmed PCa. Data were gathered from cBioPortal and UCSC Xena. Genes expressed differentially in patients with lymph node metastasis versus those without lymph node metastasis were identified. Uni-variate Cox regression analysis and LASSO Cox regression were applied to build a prediction model. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier curves were used to assess the prognostic capacity of the model, followed by external validation using the MSKCC dataset from cBioPortal. Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Results: We identified a six-gene signature (covering GSDMB, SSTR1, MX1, CCBE1, MYBPC1, and FAM3D) that could effectively identify a high-risk subset of PCa patients. ROC analysis indicated that the signature had a good performance (AUC > 0.7) in survival prediction in both the training and the testing/validation cohorts. Cox regression analysis showed that the six-gene signature could independently predict disease-free survival (DFS) as well, although with lower predictive power. Subgroup analyses showed that signature-based risk score may serve as a promising marker to predict DFS in different subgroups, including stage T2 (HR = 0.12, p < 0.001), stage T3 (HR = 0.29, p < 0.001), TP53-wild-type (HR = 0.22, p < 0.001), TP53-mutated (HR = 0.07, p < 0001), AR pathways-wild-type (HR = 0.2, p < 0.001) and AR pathways-mutated(HR = 0.16, p = 0.0419). The performance of the six-gene signature in LNM+ was stable for stratifying the patients according to risk of deatch (HR = 0.23, p = 0.0333). Moreover, GSEA revealed distinct pathway enrichment features in the different risk groups, where pathways related to DNA repair were more prominently enriched in the high-risk group while the low-risk group had higher enrichment of androgen response. Conclusions: We developed a robust six-gene signature that can effectively classify PCa patients into groups with low- and high-risk group, which may help select high-risk patients who require more aggressive adjuvant target therapy or immune therapy.

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