scholarly journals The Comprehensive Analysis of Competitive Endogenous RNA Networks and Tumor-Infiltrating Immune Cells in Gastric Cancer With Lymph Node Metastasis

Author(s):  
Fangxiao Gong ◽  
Tianyu Liang ◽  
Zongbin Lin ◽  
Renyang Liu ◽  
Jun Hong ◽  
...  

Abstract Background: Gastric cancer is a kind of tumor with strong heterogeneity. Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors. Methods: In this study, we divided all TCGA gastric cancer patients into the whole, intestinal and diffuse cohorts for further analysis, and constructed competitive endogenous RNA network and evaluated immune cells using CIBERSORTx. The support vector machines recursive feature elimination (SVM-RFE) was used for screening significant signatures and the support vector machines (SVM) for establishing model predicting the lymph node metastasis. Results: In this study, we divided all TCGA gastric cancer patients into the whole, intestinal and diffuse cohorts for further analysis, and constructed competitive endogenous RNA network and evaluated immune cells using CIBERSORTx. The support vector machines recursive feature elimination (SVM-RFE) was used for screening significant signatures and the support vector machines (SVM) for establishing model predicting the lymph node metastasis. The performance of SVM model was good in the intestinal and diffuse cohort, while the model in the whole cohort was relatively poor. Some important co-expression patterns between immune cells and ceRNAs network indicated significant correlation CD70 with dendritic cells and so on. Conclusion: Our research inferred competing endogenous RNA network of lymph node metastasis and built an excellent predicting model.

Oncogene ◽  
2021 ◽  
Vol 40 (12) ◽  
pp. 2296-2308
Author(s):  
Mei Wang ◽  
Xinxin Zhao ◽  
Rong Qiu ◽  
Zheng Gong ◽  
Feng Huang ◽  
...  

AbstractLymph node metastasis (LNM), a common metastatic gastric-cancer (GC) route, is closely related to poor prognosis in GC patients. Bone marrow-derived mesenchymal stem cells (BM-MSCs) preferentially engraft at metastatic lesions. Whether BM-MSCs are specifically reprogrammed by LNM-derived GC cells (LNM-GCs) and incorporated into metastatic LN microenvironment to prompt GC malignant progression remains unknown. Herein, we found that LNM-GCs specifically educated BM-MSCs via secretory exosomes. Exosomal Wnt5a was identified as key protein mediating LNM-GCs education of BM-MSCs, which was verified by analysis of serum exosomes collected from GC patients with LNM. Wnt5a-enriched exosomes induced YAP dephosphorylation in BM-MSCs, whereas Wnt5a-deficient exosomes exerted the opposite effect. Inhibition of YAP signaling by verteporfin blocked LNM-GC exosome- and serum exosome-mediated reprogramming in BM-MSCs. Analysis of MSC-like cells obtained from metastatic LN tissues of GC patients (GLN-MSCs) confirmed that BM-MSCs incorporated into metastatic LN microenvironment, and that YAP activation participated in maintaining their tumor-promoting phenotype and function. Collectively, our results show that LNM-GCs specifically educated BM-MSCs via exosomal Wnt5a-elicited activation of YAP signaling. This study provides new insights into the mechanisms of LNM in GC and BM-MSC reprogramming, and will provide potential therapeutic targets and detection indicators for GC patients with LNM.


Surgery Today ◽  
2015 ◽  
Vol 46 (9) ◽  
pp. 1031-1038 ◽  
Author(s):  
Satoru Ishii ◽  
Keishi Yamashita ◽  
Hiroshi Kato ◽  
Nobuyuki Nishizawa ◽  
Hideki Ushiku ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Yuejuan Xu ◽  
Jue Sun ◽  
Jianhua Xu ◽  
Qi Li ◽  
Yuewu Guo ◽  
...  

Background. Gastric cancer (GC) is an important malignant disease around the world. Abnormalities of microRNAs (miRNAs) have been implicated in carcinogenesis of various cancers. In the present study, we examined miR-21 expression in human gastric cancer with lymph node metastasis and attempted to uncover its relationship with clinicopathologic data, especially with lymph node metastasis.Materials and Methods. The expression levels of miR-21 in the tumor specimens of GC patients were quantified by RT-PCR. The correlation between miR-21 level and multiple clinicopathological factors was then examined by Mann-Whitney test, Kaplan-Meier survival analysis, and operating characteristic (ROC) analysis.Results. The expression level of miR-21 was higher in GC patients with lymph node metastasis than in those without lymph node metastasis (P<0.05). Expression level of miR-21 was significantly correlated with histologic type, T stage, lymph node metastasis and pTNM stage. The overall survival rates in GC patients with low upregulated miR-21 expression were significantly higher than those with high upregulated miR-21 (P<0.05).Conclusion. A close association is implicated between the elevated miR-21and lymph node metastasis, which could potentially be exploited as a practical biomarker for lymph node metastasis in patients with GC.


2011 ◽  
Vol 15 (2) ◽  
pp. 221-225 ◽  
Author(s):  
Hisaharu Oya ◽  
Takuji Gotoda ◽  
Tetsu Kinjo ◽  
Haruhisa Suzuki ◽  
Shigetaka Yoshinaga ◽  
...  

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