miR-204-5p Suppress Lymph Node Metastasis via Regulating CXCL12 and CXCR4 in Gastric Cancer

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Abstract

Gastric cancer (GC) exhibits a poor prognosis due to extensive invasion and lymphatic metastasis in the advanced stage. In this study, we firstly found that the expression of miR-204-5p markedly decreased in GC patients' tissue and serum, especially in GC with lymphatic metastasis. And ROC analysis showed miR-204-5p also served as a predicted factor for the lymphatic metastasis of GC. CXCL12 and CXCR4 were predicted and confirmed as the functional targets of miR-204-5p by Targetscan analysis, dual luciferase assay and western blotting analysis. In addition, we further determined that miR-204-5p suppresses migration and invasion in GC. This finding elucidates new functions and mechanisms for miR-204-5p in GC development and provides a new potential diagnostic marker and therapeutic targets for GC.

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CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment.

Jan A Burger, Thomas J Kipps (2006)

Signals from the microenvironment have a profound influence on the maintenance and/or progression of hematopoietic and epithelial cancers. Mesenchymal or marrow-derived stromal cells, which constitute a large proportion of the non-neoplastic cells within the tumor microenvironment, constitutively secrete the chemokine stromal cell-derived factor-1 (SDF-1/CXCL12). CXCL12 secretion by stromal cells attracts cancer cells, acting through its cognate receptor, CXCR4, which is expressed by both hematopoietic and nonhematopoietic tumor cells. CXCR4 promotes tumor progression by direct and indirect mechanisms. First, CXCR4 is essential for metastatic spread to organs where CXCL12 is expressed, and thereby allows tumor cells to access cellular niches, such as the marrow, that favor tumor-cell survival and growth. Second, stromal-derived CXCL12 itself can stimulate survival and growth of neoplastic cells in a paracrine fashion. Third, CXCL12 can promote tumor angiogenesis by attracting endothelial cells to the tumor microenvironment. CXCR4 expression is a prognostic marker in various types of cancer, such as acute myelogenous leukemia or breast carcinoma. Promising results in preclinical tumor models indicate that CXCR4 antagonists may have antitumor activity in patients with various malignancies. Collectively, these observations reveal that CXCR4 is an important molecule involved in the spread and progression of a variety of different tumors. As such, CXCR4 antagonists, although initially developed for treatment of AIDS, actually may become effective agents for the treatment of neoplastic disease.

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Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer.

Jianqiang Liu, Jun- Gao, Yiqi Du … (2012)

This study was performed to identify plasma microRNAs (miRNAs) as diagnostic biomarkers for pancreatic cancer (PCa) and to assess their supplementary role with serum CA19-9 in early identification of tumors. Plasma RNAs were extracted from 140 PCa patients, 111 chronic pancreatitis (CP) patients and 68 normal controls, and the relative abundances of seven miRNAs (miR-16, 21, 155, 181a, 181b, 196a and 210) were measured using real-time PCR. Their diagnostic utility for PCa and correlation with clinical characteristics were analyzed. All seven miRNAs were significantly aberrantly upregulated in the PCa group compared with both the CP and normal groups, between which only four miRNAs (miR-155, 181a, 181b and 196a) were significantly different. Logistic modeling proved that only miR-16 and miR-196a possessed an independent role in discriminating PCa from normal and CP. Furthermore, after including serum CA19-9 in the logistic model, the combination of miR-16, miR-196a and CA19-9 was more effective for discriminating PCa from non-PCa (normal+CP) (AUC-ROC, 0.979; sensitivity, 92.0%; specificity, 95.6%), and for discriminating PCa from CP (AUC-ROC, 0.956; sensitivity, 88.4%; specificity, 96.3%) compared with the miRNA panel (miR-16+miR-196a) or CA19-9 alone. Most significantly, the combination was effective at identification of tumors in Stage 1 (85.2%). In conclusion, plasma miRNAs were effective for distinguishing PCa from non-PCa (normal+CP). The combination of miR-16, miR-196a and CA19-9 was more effective for PCa diagnosis, especially in early tumor screening. Copyright © 2011 UICC.

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The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients.

Alberto Marchet, Simone Mocellin, Alessandro Ambrosi … (2007)

To investigate whether the ratio between metastatic and examined lymph nodes (N ratio) is a better prognostic factor as compared with traditional staging systems in patients with gastric cancer regardless of the extension of lymph node dissection. We retrospectively reviewed the data of 1853 patients who underwent radical resection for gastric carcinoma at 6 Italian centers. Patients with >15 (group 1, n = 1421) and those with 25%) were determined by the best cut-off approach. After a median follow-up of 45.5 months (range, 4-182 months), the 5-year overall survival of N0, N1, and N2 patients of group 1 versus group 2 was 83.4% versus 74.2% (P = 0.0026), 54.3% versus 44.3% (P = 0.018), and 32.7% versus 14.7% (P = 0.004), respectively, suggesting that a low number of excised lymph nodes can lead to the understaging of patients. N ratio identified subsets of patients with significantly different survival rates within N1 and N2 stages in both groups. At multivariate analysis, the N ratio (but not N stage) was retained as an independent prognostic factor both in group 1 and group 2 (HR for N ratio 1, N ratio 2, and N ratio 3 = 1.67, 2.96, and 6.59, and 1.56, 2.68, and 4.28, respectively). In our series, the implementation of N ratio led to the identification of subgroups of patients prognostically more homogeneous than those classified by the TNM system. N ratio is a simple and reproducible prognostic tool that can stratify patients with gastric cancer also in case of limited lymph node dissection. These data may represent the rational for improving the prognostic power of current UICC TNM staging system and ultimately the selection of patients who may most benefit from adjuvant treatments.

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Author and article information

Journal

Journal ID (nlm-ta): J Cancer

Journal ID (iso-abbrev): J Cancer

Journal ID (publisher-id): jca

Title: Journal of Cancer

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1837-9664

Publication date Collection: 2020

Publication date (Electronic): 5 March 2020

Volume: 11

Issue: 11

Pages: 3199-3206

Affiliations

[1 ]Department of Gastroenterology, The First Affiliated Hospital of Xi'an JiaoTong University, 277 Yanta West Road, Xi'an, Shaanxi, China.

[2 ]Department of Gastroenterology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China.

[3 ]Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.

[4 ]Department of Gastroenterology, Kunshan traditional Chinese medicine hospital. Jiangsu, China.

[5 ]Department of General Surgery, The First Affiliated Hospital of Xi'an Jiao Tong University, 277 Yanta West Road, Xi'an, Shaanxi, China.

[6 ]Institute of Oncology, Second Affiliated Hospital, Xi'an Medical College, China.

Author notes

✉ Corresponding authors: Jun Gao, MD, PhD (E-mail: 13816012151@ 123456163.com ) & Shuixiang He, MD (E-mail: dyyyjxk@ 123456mail.xjtu.edu.cn ).

#These authors contributed equally to this work.

Competing Interests: The authors have declared that no competing interest exists.

Article

Publisher ID: jcav11p3199

DOI: 10.7150/jca.33273

PMC ID: 7097947

PubMed ID: 32231725

SO-VID: 32ae467c-d209-468e-a87e-ffd8afe979cb

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This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

miR-204-5p Suppress Lymph Node Metastasis via Regulating CXCL12 and CXCR4 in Gastric Cancer

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Most cited references 26

CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment.

Combination of plasma microRNAs with serum CA19-9 for early detection of pancreatic cancer.

The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients.

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