Development and validation of an individualized angiogenesis and tumor-infiltrating lymphocytes prognostic signature in nasopharyngeal carcinoma

In recent years, targeted therapy and immunotherapy have become ideal choices for the treatment of advanced, metastatic, recurrent, and drug-resistant nasopharyngeal carcinoma (NPC), but the lack of understanding of the relationship and mechanism between TILs and angiogenic factors hinders therapeut...

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Veröffentlicht in:Pathology, research and practice research and practice, 2024-01, Vol.253, p.154936-154936, Article 154936
Hauptverfasser: Zhang, Ruyun, Liao, Xiaofei, Zhang, Bin, Huang, Xiaohong, Qin, Guanjie, Kong, Xiangyun, Xie, Yuan, Mo, Yunyan, Dai, Jinxuan, Gan, Chunqiao, Luo, Zan, Lu, Jingyan, Jiang, Wei
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container_title Pathology, research and practice
container_volume 253
creator Zhang, Ruyun
Liao, Xiaofei
Zhang, Bin
Huang, Xiaohong
Qin, Guanjie
Kong, Xiangyun
Xie, Yuan
Mo, Yunyan
Dai, Jinxuan
Gan, Chunqiao
Luo, Zan
Lu, Jingyan
Jiang, Wei
description In recent years, targeted therapy and immunotherapy have become ideal choices for the treatment of advanced, metastatic, recurrent, and drug-resistant nasopharyngeal carcinoma (NPC), but the lack of understanding of the relationship and mechanism between TILs and angiogenic factors hinders therapeutic development and optimization. In this study, the expression of angiogenesis-related markers (VEGF-A,VEGFR-2) and TILs (CD4+T,CD8+T) was studied by using immunohistochemistry (IHC). Then we constructed an immunohistochemical scoring model for the co-expression of angiogenesis-related markers and TILs (COV+TIL score)in the training (n = 124) and validated the accuracy and reliability of the scoring system in the validation cohorts (n = 114), respectively We established the COV+TIL score model and stratified patients into different risk level in the training cohorts according to COV+TIL score (cut-off value=28). Patients in the high-risk group had worse prognosis in the training cohorts five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) was lower than that of patients in the low-risk group, and this result was validated in the validation cohorts ( 5-year OS in the high-risk and the low-risk group 46.8% vs. 83.4%, HR: 3.42, 95%CI: 1.77–6.61, p 
doi_str_mv 10.1016/j.prp.2023.154936
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In this study, the expression of angiogenesis-related markers (VEGF-A,VEGFR-2) and TILs (CD4+T,CD8+T) was studied by using immunohistochemistry (IHC). Then we constructed an immunohistochemical scoring model for the co-expression of angiogenesis-related markers and TILs (COV+TIL score)in the training (n = 124) and validated the accuracy and reliability of the scoring system in the validation cohorts (n = 114), respectively We established the COV+TIL score model and stratified patients into different risk level in the training cohorts according to COV+TIL score (cut-off value=28). Patients in the high-risk group had worse prognosis in the training cohorts five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) was lower than that of patients in the low-risk group, and this result was validated in the validation cohorts ( 5-year OS in the high-risk and the low-risk group 46.8% vs. 83.4%, HR: 3.42, 95%CI: 1.77–6.61, p &lt; 0.001); ( 5-year PFS 45.9% vs. 81.2%, HR: 3.22, 95%CI: 1.71–6.06, p &lt; 0.001); ( 5-year LRRFS 74.6% vs. 87.5%, HR: 3.22, 95%CI: 1.16–8.93, p = 0.027); and ( 5-year DMFS79.2% vs. 93.2%, HR: 2.22, 95%CI: 0.91–5.39, p = 0.086). Upon multivariable analysis, COV+TIL score emerged as an independent prognostic indicator for defining survival in the training cohorts and the validation cohorts. Combining the COV+TIL score and TNM stage improved the prediction ability of the survival. In conclusion, NPC patients with high COV+TIL score showed worse prognosis.</description><identifier>ISSN: 0344-0338</identifier><identifier>EISSN: 1618-0631</identifier><identifier>DOI: 10.1016/j.prp.2023.154936</identifier><identifier>PMID: 38006840</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Angiogenesis ; Nasopharyngeal carcinoma ; Prognosis,biomarker ; Tumor-infiltrating lymphocytes</subject><ispartof>Pathology, research and practice, 2024-01, Vol.253, p.154936-154936, Article 154936</ispartof><rights>2023 Elsevier GmbH</rights><rights>Copyright © 2023 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c305t-c46280728a34fb751c69cc187a949f6d6875bea2e74c95b27276d7c9515639003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0344033823006374$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38006840$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Ruyun</creatorcontrib><creatorcontrib>Liao, Xiaofei</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Huang, Xiaohong</creatorcontrib><creatorcontrib>Qin, Guanjie</creatorcontrib><creatorcontrib>Kong, Xiangyun</creatorcontrib><creatorcontrib>Xie, Yuan</creatorcontrib><creatorcontrib>Mo, Yunyan</creatorcontrib><creatorcontrib>Dai, Jinxuan</creatorcontrib><creatorcontrib>Gan, Chunqiao</creatorcontrib><creatorcontrib>Luo, Zan</creatorcontrib><creatorcontrib>Lu, Jingyan</creatorcontrib><creatorcontrib>Jiang, Wei</creatorcontrib><title>Development and validation of an individualized angiogenesis and tumor-infiltrating lymphocytes prognostic signature in nasopharyngeal carcinoma</title><title>Pathology, research and practice</title><addtitle>Pathol Res Pract</addtitle><description>In recent years, targeted therapy and immunotherapy have become ideal choices for the treatment of advanced, metastatic, recurrent, and drug-resistant nasopharyngeal carcinoma (NPC), but the lack of understanding of the relationship and mechanism between TILs and angiogenic factors hinders therapeutic development and optimization. In this study, the expression of angiogenesis-related markers (VEGF-A,VEGFR-2) and TILs (CD4+T,CD8+T) was studied by using immunohistochemistry (IHC). Then we constructed an immunohistochemical scoring model for the co-expression of angiogenesis-related markers and TILs (COV+TIL score)in the training (n = 124) and validated the accuracy and reliability of the scoring system in the validation cohorts (n = 114), respectively We established the COV+TIL score model and stratified patients into different risk level in the training cohorts according to COV+TIL score (cut-off value=28). Patients in the high-risk group had worse prognosis in the training cohorts five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) was lower than that of patients in the low-risk group, and this result was validated in the validation cohorts ( 5-year OS in the high-risk and the low-risk group 46.8% vs. 83.4%, HR: 3.42, 95%CI: 1.77–6.61, p &lt; 0.001); ( 5-year PFS 45.9% vs. 81.2%, HR: 3.22, 95%CI: 1.71–6.06, p &lt; 0.001); ( 5-year LRRFS 74.6% vs. 87.5%, HR: 3.22, 95%CI: 1.16–8.93, p = 0.027); and ( 5-year DMFS79.2% vs. 93.2%, HR: 2.22, 95%CI: 0.91–5.39, p = 0.086). Upon multivariable analysis, COV+TIL score emerged as an independent prognostic indicator for defining survival in the training cohorts and the validation cohorts. Combining the COV+TIL score and TNM stage improved the prediction ability of the survival. In conclusion, NPC patients with high COV+TIL score showed worse prognosis.</description><subject>Angiogenesis</subject><subject>Nasopharyngeal carcinoma</subject><subject>Prognosis,biomarker</subject><subject>Tumor-infiltrating lymphocytes</subject><issn>0344-0338</issn><issn>1618-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9UU1v1DAUtBAV3RZ-ABeUI5cs_ortiBMqLUWq1AucLa_9knqV2MF2Vlp-BT8ZL1s4cnpPo5nRvDcIvSV4SzARH_bbJS1biinbko73TLxAGyKIarFg5CXaYMZ5ixlTl-gq5z3GWGJOXqFLpjAWiuMN-vUZDjDFZYZQGhNcczCTd6b4GJo4VKTxwfmDd2vFf4KryOjjCAGyz38EZZ1jan0Y_FRSFYaxmY7z8hTtsUBulhTHEHPxtsl-DKasCapnE0yOy5NJxzCCmRprkvUhzuY1uhjMlOHN87xG3-9uv93ctw-PX77efHpoLcNdaS0XVGFJlWF82MmOWNFbS5Q0Pe8H4YSS3Q4MBclt3-2opFI4WVfSCdZjzK7R-7NvDfhjhVz07LOFaTIB4po1VT1TnBJ1opIz1aaYc4JBL8nPNbomWJ-K0PuKLPpUhD4XUTXvnu3X3Qzun-Lv5yvh45kA9ciDh6Sz9RAsOJ_AFu2i_4_9b77wnJI</recordid><startdate>202401</startdate><enddate>202401</enddate><creator>Zhang, Ruyun</creator><creator>Liao, Xiaofei</creator><creator>Zhang, Bin</creator><creator>Huang, Xiaohong</creator><creator>Qin, Guanjie</creator><creator>Kong, Xiangyun</creator><creator>Xie, Yuan</creator><creator>Mo, Yunyan</creator><creator>Dai, Jinxuan</creator><creator>Gan, Chunqiao</creator><creator>Luo, Zan</creator><creator>Lu, Jingyan</creator><creator>Jiang, Wei</creator><general>Elsevier GmbH</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202401</creationdate><title>Development and validation of an individualized angiogenesis and tumor-infiltrating lymphocytes prognostic signature in nasopharyngeal carcinoma</title><author>Zhang, Ruyun ; Liao, Xiaofei ; Zhang, Bin ; Huang, Xiaohong ; Qin, Guanjie ; Kong, Xiangyun ; Xie, Yuan ; Mo, Yunyan ; Dai, Jinxuan ; Gan, Chunqiao ; Luo, Zan ; Lu, Jingyan ; Jiang, Wei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c305t-c46280728a34fb751c69cc187a949f6d6875bea2e74c95b27276d7c9515639003</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Angiogenesis</topic><topic>Nasopharyngeal carcinoma</topic><topic>Prognosis,biomarker</topic><topic>Tumor-infiltrating lymphocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Ruyun</creatorcontrib><creatorcontrib>Liao, Xiaofei</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Huang, Xiaohong</creatorcontrib><creatorcontrib>Qin, Guanjie</creatorcontrib><creatorcontrib>Kong, Xiangyun</creatorcontrib><creatorcontrib>Xie, Yuan</creatorcontrib><creatorcontrib>Mo, Yunyan</creatorcontrib><creatorcontrib>Dai, Jinxuan</creatorcontrib><creatorcontrib>Gan, Chunqiao</creatorcontrib><creatorcontrib>Luo, Zan</creatorcontrib><creatorcontrib>Lu, Jingyan</creatorcontrib><creatorcontrib>Jiang, Wei</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pathology, research and practice</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Ruyun</au><au>Liao, Xiaofei</au><au>Zhang, Bin</au><au>Huang, Xiaohong</au><au>Qin, Guanjie</au><au>Kong, Xiangyun</au><au>Xie, Yuan</au><au>Mo, Yunyan</au><au>Dai, Jinxuan</au><au>Gan, Chunqiao</au><au>Luo, Zan</au><au>Lu, Jingyan</au><au>Jiang, Wei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development and validation of an individualized angiogenesis and tumor-infiltrating lymphocytes prognostic signature in nasopharyngeal carcinoma</atitle><jtitle>Pathology, research and practice</jtitle><addtitle>Pathol Res Pract</addtitle><date>2024-01</date><risdate>2024</risdate><volume>253</volume><spage>154936</spage><epage>154936</epage><pages>154936-154936</pages><artnum>154936</artnum><issn>0344-0338</issn><eissn>1618-0631</eissn><abstract>In recent years, targeted therapy and immunotherapy have become ideal choices for the treatment of advanced, metastatic, recurrent, and drug-resistant nasopharyngeal carcinoma (NPC), but the lack of understanding of the relationship and mechanism between TILs and angiogenic factors hinders therapeutic development and optimization. In this study, the expression of angiogenesis-related markers (VEGF-A,VEGFR-2) and TILs (CD4+T,CD8+T) was studied by using immunohistochemistry (IHC). Then we constructed an immunohistochemical scoring model for the co-expression of angiogenesis-related markers and TILs (COV+TIL score)in the training (n = 124) and validated the accuracy and reliability of the scoring system in the validation cohorts (n = 114), respectively We established the COV+TIL score model and stratified patients into different risk level in the training cohorts according to COV+TIL score (cut-off value=28). Patients in the high-risk group had worse prognosis in the training cohorts five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) was lower than that of patients in the low-risk group, and this result was validated in the validation cohorts ( 5-year OS in the high-risk and the low-risk group 46.8% vs. 83.4%, HR: 3.42, 95%CI: 1.77–6.61, p &lt; 0.001); ( 5-year PFS 45.9% vs. 81.2%, HR: 3.22, 95%CI: 1.71–6.06, p &lt; 0.001); ( 5-year LRRFS 74.6% vs. 87.5%, HR: 3.22, 95%CI: 1.16–8.93, p = 0.027); and ( 5-year DMFS79.2% vs. 93.2%, HR: 2.22, 95%CI: 0.91–5.39, p = 0.086). Upon multivariable analysis, COV+TIL score emerged as an independent prognostic indicator for defining survival in the training cohorts and the validation cohorts. Combining the COV+TIL score and TNM stage improved the prediction ability of the survival. In conclusion, NPC patients with high COV+TIL score showed worse prognosis.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>38006840</pmid><doi>10.1016/j.prp.2023.154936</doi><tpages>1</tpages></addata></record>
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subjects Angiogenesis
Nasopharyngeal carcinoma
Prognosis,biomarker
Tumor-infiltrating lymphocytes
title Development and validation of an individualized angiogenesis and tumor-infiltrating lymphocytes prognostic signature in nasopharyngeal carcinoma
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