Evidence map›Paper›PMID 39107788›Full record

ArticleJournal of translational medicine2024

Vasorin (VASN) overexpression promotes pulmonary metastasis and resistance to adjuvant chemotherapy in patients with locally advanced rectal cancer.

Da Kang, Shanshan Huang, Yijun Liao, Siyuan Mi, Jingying Zhou, Yu Feng, Riming Huang, Zhen-Hai Lu, Z Z Pan, Wenjuan Ma and 4 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Da Kang *Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, P. R. China.
Shanshan Huang *State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.
Yijun Liao *Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, P. R. China.
Siyuan Mi *Department of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, P. R. China.
Jingying ZhouSchool of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong SAR, 999077, China.
Yu FengBGI-Shenzhen, Shenzhen, 519103, P. R. China.
Riming HuangGuangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou, 510642, China.
Zhen-Hai LuDepartment of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, P. R. China.
Z Z PanDepartment of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, P. R. China.
Wenjuan MaState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China.
Gong ChenDepartment of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, P. R. China. chengong@sysucc.org.cn.
Jia-Xing YueState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China. yuejiaxing@gmail.com.
Jingxiu HuangState Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China. huangjx@sysucc.org.cn.
R X ZhangDepartment of Colorectal Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Centre, Guangzhou, Guangdong, 510060, P. R. China. zhangrx@sysucc.org.cn.

Funding

Basic and Applied Basic Research Foundation of Guangdong Province 2021A1515010096Basic and Applied Basic Research Foundation of Guangdong Province 2022A1515010717Basic and Applied Basic Research Foundation of Guangdong Province 2023A1515010243Chinese Society of Clinical Oncology Y-HR2018-319Chinese Society of Clinical Oncology Y-JS2019-009Chinese Society of Clinical Oncology Y-L2017-002Guangdong Provincial Pearl River Talents Program 2019QN01Y183Guangzhou Medical University 202011-103Guangzhou Medical University 202301-314National Natural Science Foundation of China 32070592National Natural Science Foundation of China 82002628Sun Yat-sen University 19ykpy180Sun Yat-sen University 201313Sun Yat-sen University YTP-SYSUCC-0042
6 · The paper itself

Abstract

backgroundLARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection.

methodsSequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome.

resultsOur study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer.

conclusionsOur study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.

Indexed as

Drug Resistance, NeoplasmLung NeoplasmsRectal NeoplasmsAnimalsCell Line, TumorCell ProliferationChemotherapy, AdjuvantFemaleGene Expression Regulation, NeoplasticHumansMaleMAP Kinase Signaling SystemMice, NudeMicrofilament ProteinsMiddle AgedReceptor, Notch1Microfilament ProteinsReceptor, Notch1Adjuvant therapyMAPK pathwayNOTCH pathwayPulmonary metastasisRectal cancer

Identifiers

PMID39107788
PMCPMC11301854

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.