CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer

Patients of colorectal cancer (CRC) with BRAF V600E mutation obtain poor prognosis. This study aimed to explore the role and mechanism of BRAF V600E mutation in angiogenesis of tumor micro-environment (TME). It has been reported that CXCL16 expression in TME is closely related to BRAF mutation. Clin...

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Main Authors: Weihao Deng, Xiaoxia Liu, Shuhui Huang, Zhijie Wu, Fichera Alessandro, Qingfeng Lin, Zonglu Cai, Zitong Zhang, Yan Huang, Hui Wang, Zixu Yuan
Format: Article
Language:English
Published: Elsevier 2024-03-01
Series:Translational Oncology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1936523323002401
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author Weihao Deng
Xiaoxia Liu
Shuhui Huang
Zhijie Wu
Fichera Alessandro
Qingfeng Lin
Zonglu Cai
Zitong Zhang
Yan Huang
Hui Wang
Zixu Yuan
author_facet Weihao Deng
Xiaoxia Liu
Shuhui Huang
Zhijie Wu
Fichera Alessandro
Qingfeng Lin
Zonglu Cai
Zitong Zhang
Yan Huang
Hui Wang
Zixu Yuan
author_sort Weihao Deng
collection DOAJ
description Patients of colorectal cancer (CRC) with BRAF V600E mutation obtain poor prognosis. This study aimed to explore the role and mechanism of BRAF V600E mutation in angiogenesis of tumor micro-environment (TME). It has been reported that CXCL16 expression in TME is closely related to BRAF mutation. Clinicopathological features of CRC with BRAF V600E mutant or wild type were collected in this study. Immunohistochemistry (IHC) assays were conducted to test the expressions of vascular endothelial growth factor (VEGF), CD31 and CXCL16. ROC curve was used to determine the optimal cut off values of CXCL16. A total of 680 patients including 141 BRAF V600E type and 679 wild type were included. BRAF V600E mutant tumors were presented with significant worse clinicopathological features and a shorter overall survival (OS) than wild-type. Besides, chemokines CXCL16 was up-regulated in BRAF V600E mutant tissues and was associated with poorer prognosis. In addition, VEGF levels and vascular endothelial cell density was significantly increased in BRAF mutation. At last, CXCL16 was positively correlated with VEGF expression and vascular endothelial cell density. In conclusion, BRAF V600E mutations may promote metastasis of CRC by regulating CXCL16 expression and promoting angiogenesis in the TME.
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spelling doaj.art-d71361668e20495c8a7a6db3e7531a342024-02-05T04:31:36ZengElsevierTranslational Oncology1936-52332024-03-0141101854CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancerWeihao Deng0Xiaoxia Liu1Shuhui Huang2Zhijie Wu3Fichera Alessandro4Qingfeng Lin5Zonglu Cai6Zitong Zhang7Yan Huang8Hui Wang9Zixu Yuan10Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Department of General Surgery, Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, ChinaDepartment of Pathology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Department of General Surgery, Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, ChinaColon and Rectal Surgery, Baylor University Medical Center, TX, United States of AmericaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Department of General Surgery, Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, ChinaGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Department of General Surgery, Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, ChinaDepartment of General Surgery, Houjie Hospital, Dongguan, Guangdong, China; Corresponding author at: Rt. 21 Hetian, Dongguan, Guangdong, China.Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Corresponding authors at: No. 26, Erheng Road, Yuancun, Guangzhou 510655, China.Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Department of General Surgery, Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Corresponding authors at: No. 26, Erheng Road, Yuancun, Guangzhou 510655, China.Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Department of General Surgery, Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, China; Corresponding authors at: No. 26, Erheng Road, Yuancun, Guangzhou 510655, China.Patients of colorectal cancer (CRC) with BRAF V600E mutation obtain poor prognosis. This study aimed to explore the role and mechanism of BRAF V600E mutation in angiogenesis of tumor micro-environment (TME). It has been reported that CXCL16 expression in TME is closely related to BRAF mutation. Clinicopathological features of CRC with BRAF V600E mutant or wild type were collected in this study. Immunohistochemistry (IHC) assays were conducted to test the expressions of vascular endothelial growth factor (VEGF), CD31 and CXCL16. ROC curve was used to determine the optimal cut off values of CXCL16. A total of 680 patients including 141 BRAF V600E type and 679 wild type were included. BRAF V600E mutant tumors were presented with significant worse clinicopathological features and a shorter overall survival (OS) than wild-type. Besides, chemokines CXCL16 was up-regulated in BRAF V600E mutant tissues and was associated with poorer prognosis. In addition, VEGF levels and vascular endothelial cell density was significantly increased in BRAF mutation. At last, CXCL16 was positively correlated with VEGF expression and vascular endothelial cell density. In conclusion, BRAF V600E mutations may promote metastasis of CRC by regulating CXCL16 expression and promoting angiogenesis in the TME.http://www.sciencedirect.com/science/article/pii/S1936523323002401CXCL16BRAF V600E mutantColorectal cancerTumor micro-environmentAngiogenesis
spellingShingle Weihao Deng
Xiaoxia Liu
Shuhui Huang
Zhijie Wu
Fichera Alessandro
Qingfeng Lin
Zonglu Cai
Zitong Zhang
Yan Huang
Hui Wang
Zixu Yuan
CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer
Translational Oncology
CXCL16
BRAF V600E mutant
Colorectal cancer
Tumor micro-environment
Angiogenesis
title CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer
title_full CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer
title_fullStr CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer
title_full_unstemmed CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer
title_short CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer
title_sort cxcl16 promotes tumor metastasis by regulating angiogenesis in the tumor micro environment of braf v600e mutant colorectal cancer
topic CXCL16
BRAF V600E mutant
Colorectal cancer
Tumor micro-environment
Angiogenesis
url http://www.sciencedirect.com/science/article/pii/S1936523323002401
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