Expression and prognostic impact of PRL‐3 in lymph node metastasis of gastric cancer: Its molecular mechanism was investigated using artificial microRNA interference

54 Background: Tumor associated macrophages (TAMs) are major components of tumor environment, and polarized into M1 and M2 type. M1 has been known as antitumorigenic, whereas M2 as protumorigenic. M2 have a significant role in tumor progression by promoting tumor cell invasion, migration and angiogenesis. We evaluated the M2 macrophages to investigate its importance in predicting clinical outcome or prognosis, and the relationship between M2 and angiogenesis in patients with gastric cancer. Methods: Formalin-fixed, paraffin-embedded blocks were obtained from the 88 patients with gastric cancer. CD163+ TAMs and CD105+ vessels were evaluated by immunohistochemical staining and the extent of CD163+ TAMs in tumor were divided into three groups: (A) infiltrated TAMs in cancer cell nest (nest TAMs); (B) infiltrated TAMs in tumor stroma (stroma TAMs); and (C) infiltrated TAMs along the invasive margin of a tumor (margin TAMs). Results: The increased stroma and margin TAMs (>72 and >102, respectively) were closely correlated with lymph node metastasis, TNM stage and lymphatic invasion (p<0.05 in 3 factors) and positive correlation existed between the stroma and margin TAMs (p<0.001). Disease-free survival rate analyzed using the Kaplan– Meier method was significantly lower in patient with high stroma and margin TMAs than patient with low stroma and margin TAMs (p=0.0039 and 0.0499, respectively). CD105+ vessels showed significant correlation with lymph node metastasis and lymphatic invasion.(p=0.006 and p<0.0001, respectively) Stromal, marginal and nest TAMs were positively correlated with CD105+ vessels (p=0.001). Conclusions: M2 infiltration in tumor stroma and tumor margin in gastric cancer showed relationship with aggressive phenotypes such as lymph node metastasis, TNM stage and lymphatic invasion and was correlated with angiogenesis. This study supports the view that the adverse prognostic impact of M2 involves tumor angiogenesis in gastric cancer.

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Incidence and Prognostic Impact of Lymph Node Metastasis in Gastric Cancer: Deep Inside of Signet Ring Cell Histotype

European Journal of Surgical Oncology ◽

10.1016/j.ejso.2019.11.364 ◽

2020 ◽

Vol 46 (2) ◽

pp. e138

Author(s):

Luigi Marano ◽

Karol Polom ◽

Alessia D’Ignazio ◽

Daniele Marrelli ◽

Franco Roviello

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Signet Ring Cell ◽

Prognostic Impact ◽

Node Metastasis ◽

Signet Ring ◽

Ring Cell

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Lymph node metastasis-derived gastric cancer cells educate bone marrow-derived mesenchymal stem cells via YAP signaling activation by exosomal Wnt5a

Oncogene ◽

10.1038/s41388-021-01722-8 ◽

2021 ◽

Vol 40 (12) ◽

pp. 2296-2308

Author(s):

Mei Wang ◽

Xinxin Zhao ◽

Rong Qiu ◽

Zheng Gong ◽

Feng Huang ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Metastatic Gastric Cancer ◽

Gastric Cancer Cells ◽

Node Metastasis ◽

Signaling Activation

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.

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Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer

Current Oncology ◽

10.3390/curroncol28030155 ◽

2021 ◽

Vol 28 (3) ◽

pp. 1663-1672

Author(s):

Satomi Hattori ◽

Nobuhisa Yoshikawa ◽

Kazumasa Mogi ◽

Kosuke Yoshida ◽

Masato Yoshihara ◽

...

Keyword(s):

Cervical Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Tumor Size ◽

Concurrent Chemoradiotherapy ◽

Primary Treatment ◽

Prognostic Impact ◽

Primary Tumor Size ◽

Node Metastasis ◽

Aortic Lymph Node

(1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor >6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028); the corresponding five-year OS rates in patients with a tumor ≤6.9 and >6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

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Evaluation of lymph node metastasis in patients with gastric cancer: a comparison of the directionality of lymph node metastasis and the total number of metastatic lymph nodes

Surgery Today ◽

10.1007/s00595-012-0454-8 ◽

2012 ◽

Vol 43 (2) ◽

pp. 130-135 ◽

Cited By ~ 3

Author(s):

Maki Kitagawa ◽

Daisuke Ichikawa ◽

Shuhei Komatsu ◽

Kazuma Okamoto ◽

Atsushi Shiozaki ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Lymph Nodes ◽

Metastatic Lymph Nodes ◽

Node Metastasis ◽

Metastatic Lymph

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Predictive factors for lymph node metastasis in additional gastrectomy after endoscopic resection of cT1aN0 gastric cancer

Surgery Today ◽

10.1007/s00595-015-1281-5 ◽

2015 ◽

Vol 46 (9) ◽

pp. 1031-1038 ◽

Cited By ~ 7

Author(s):

Satoru Ishii ◽

Keishi Yamashita ◽

Hiroshi Kato ◽

Nobuyuki Nishizawa ◽

Hideki Ushiku ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Endoscopic Resection ◽

Predictive Factors ◽

Node Metastasis ◽

Additional Gastrectomy

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miR-21 Is a Promising Novel Biomarker for Lymph Node Metastasis in Patients with Gastric Cancer

Gastroenterology Research and Practice ◽

10.1155/2012/640168 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 18

Author(s):

Yuejuan Xu ◽

Jue Sun ◽

Jianhua Xu ◽

Qi Li ◽

Yuewu Guo ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Malignant Disease ◽

Close Association ◽

Survival Rates ◽

Expression Level ◽

Human Gastric Cancer ◽

Node Metastasis ◽

Kaplan Meier

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.

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