{"title":"肺大细胞神经内分泌癌的分子亚型和预后因素。","authors":"Tingting Liu, Xueyuan Chen, Silang Mo, Ting Zhou, Wenjuan Ma, Gang Chen, Xiang Chen, Mengting Shi, Yuwen Yang, Yan Huang, Hongyun Zhao, Wenfeng Fang, Yunpeng Yang, Jing Li, Li Zhang, Yuanyuan Zhao","doi":"10.21037/tlcr-24-292","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lung large cell neuroendocrine carcinoma (LCNEC) is an aggressive disease with poor prognosis and short-term survival, which lacks effective prognostic indicators. The study aims to investigate the molecular subtypes and prognostic markers of lung LCNEC.</p><p><strong>Methods: </strong>Patients diagnosed with lung LCNEC at Sun Yat-sen University Cancer Center (SYSUCC) between November 2007 and January 2021 were screened. Baseline clinical data were collected and routine blood indexes including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were calculated. Immunohistochemistry (IHC) of ASCL1, NEUROD1, POU2F3, YAP1 were done to perform molecular subtyping, while CD56, Syn, CgA, CD3, CD8, CD20, CD68, and CD163 were also stained on tissue samples. Then prognostic factors of lung LCNEC were explored.</p><p><strong>Results: </strong>One hundred and fifty-one lung LCNEC patients were identified, 103 of whom had complete clinical information, available routine blood and biochemical indexes were eventually included in the present study. Tumor tissue specimens were available from 64 patients. Positive expression rates of ASCL1, NEUROD1, and YAP1 were 82.8%, 50.0%, and 28.1%, respectively. No POU2F3<sup>+</sup> cases were detected. Forty (62.5%) patients co-expressed with two or three markers. High LMR (>3.3) was an independent predictor of favorable prognosis of disease-free survival (DFS) [hazard ratio (HR), 0.391; 95% confidence interval (CI): 0.161-0.948; P=0.04] and overall survival (OS) (HR, 0.201; 95% CI: 0.071-0.574; P=0.003). Notably, high LMR was correlated with higher intra-tumoral CD3<sup>+</sup> (P=0.004), CD8<sup>+</sup> (P=0.01), and CD68<sup>+</sup> (P<0.001) immune cell infiltration compared to low LMR in lung LCNEC.</p><p><strong>Conclusions: </strong>Our study validated molecular subtypes by IHC in lung LCNEC, and co-expression was found among different subtypes, with no prognostic effect. High blood LMR level was associated with a favorable prognosis in lung LCNEC, which might partly reflect a hot tumor tissue immune microenvironment. Our findings may benefit clinical practice, and further studies are warranted.</p>","PeriodicalId":23271,"journal":{"name":"Translational lung cancer research","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484736/pdf/","citationCount":"0","resultStr":"{\"title\":\"Molecular subtypes and prognostic factors of lung large cell neuroendocrine carcinoma.\",\"authors\":\"Tingting Liu, Xueyuan Chen, Silang Mo, Ting Zhou, Wenjuan Ma, Gang Chen, Xiang Chen, Mengting Shi, Yuwen Yang, Yan Huang, Hongyun Zhao, Wenfeng Fang, Yunpeng Yang, Jing Li, Li Zhang, Yuanyuan Zhao\",\"doi\":\"10.21037/tlcr-24-292\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Lung large cell neuroendocrine carcinoma (LCNEC) is an aggressive disease with poor prognosis and short-term survival, which lacks effective prognostic indicators. The study aims to investigate the molecular subtypes and prognostic markers of lung LCNEC.</p><p><strong>Methods: </strong>Patients diagnosed with lung LCNEC at Sun Yat-sen University Cancer Center (SYSUCC) between November 2007 and January 2021 were screened. Baseline clinical data were collected and routine blood indexes including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were calculated. Immunohistochemistry (IHC) of ASCL1, NEUROD1, POU2F3, YAP1 were done to perform molecular subtyping, while CD56, Syn, CgA, CD3, CD8, CD20, CD68, and CD163 were also stained on tissue samples. Then prognostic factors of lung LCNEC were explored.</p><p><strong>Results: </strong>One hundred and fifty-one lung LCNEC patients were identified, 103 of whom had complete clinical information, available routine blood and biochemical indexes were eventually included in the present study. Tumor tissue specimens were available from 64 patients. Positive expression rates of ASCL1, NEUROD1, and YAP1 were 82.8%, 50.0%, and 28.1%, respectively. No POU2F3<sup>+</sup> cases were detected. Forty (62.5%) patients co-expressed with two or three markers. High LMR (>3.3) was an independent predictor of favorable prognosis of disease-free survival (DFS) [hazard ratio (HR), 0.391; 95% confidence interval (CI): 0.161-0.948; P=0.04] and overall survival (OS) (HR, 0.201; 95% CI: 0.071-0.574; P=0.003). Notably, high LMR was correlated with higher intra-tumoral CD3<sup>+</sup> (P=0.004), CD8<sup>+</sup> (P=0.01), and CD68<sup>+</sup> (P<0.001) immune cell infiltration compared to low LMR in lung LCNEC.</p><p><strong>Conclusions: </strong>Our study validated molecular subtypes by IHC in lung LCNEC, and co-expression was found among different subtypes, with no prognostic effect. High blood LMR level was associated with a favorable prognosis in lung LCNEC, which might partly reflect a hot tumor tissue immune microenvironment. Our findings may benefit clinical practice, and further studies are warranted.</p>\",\"PeriodicalId\":23271,\"journal\":{\"name\":\"Translational lung cancer research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2024-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484736/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational lung cancer research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.21037/tlcr-24-292\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/9/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational lung cancer research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/tlcr-24-292","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Molecular subtypes and prognostic factors of lung large cell neuroendocrine carcinoma.
Background: Lung large cell neuroendocrine carcinoma (LCNEC) is an aggressive disease with poor prognosis and short-term survival, which lacks effective prognostic indicators. The study aims to investigate the molecular subtypes and prognostic markers of lung LCNEC.
Methods: Patients diagnosed with lung LCNEC at Sun Yat-sen University Cancer Center (SYSUCC) between November 2007 and January 2021 were screened. Baseline clinical data were collected and routine blood indexes including lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were calculated. Immunohistochemistry (IHC) of ASCL1, NEUROD1, POU2F3, YAP1 were done to perform molecular subtyping, while CD56, Syn, CgA, CD3, CD8, CD20, CD68, and CD163 were also stained on tissue samples. Then prognostic factors of lung LCNEC were explored.
Results: One hundred and fifty-one lung LCNEC patients were identified, 103 of whom had complete clinical information, available routine blood and biochemical indexes were eventually included in the present study. Tumor tissue specimens were available from 64 patients. Positive expression rates of ASCL1, NEUROD1, and YAP1 were 82.8%, 50.0%, and 28.1%, respectively. No POU2F3+ cases were detected. Forty (62.5%) patients co-expressed with two or three markers. High LMR (>3.3) was an independent predictor of favorable prognosis of disease-free survival (DFS) [hazard ratio (HR), 0.391; 95% confidence interval (CI): 0.161-0.948; P=0.04] and overall survival (OS) (HR, 0.201; 95% CI: 0.071-0.574; P=0.003). Notably, high LMR was correlated with higher intra-tumoral CD3+ (P=0.004), CD8+ (P=0.01), and CD68+ (P<0.001) immune cell infiltration compared to low LMR in lung LCNEC.
Conclusions: Our study validated molecular subtypes by IHC in lung LCNEC, and co-expression was found among different subtypes, with no prognostic effect. High blood LMR level was associated with a favorable prognosis in lung LCNEC, which might partly reflect a hot tumor tissue immune microenvironment. Our findings may benefit clinical practice, and further studies are warranted.
期刊介绍：
Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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