Tumor‐derived Vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and T‐cell‐inflamed phenotype in small cell lung cancer
Abstract Despite recent progress in subtype classification for small cell lung carcinoma (SCLC), little is known about the biomarker for triple‐negative (ASCL1, NEUROD1, and POU2F3 negative) tumors. The long‐term survival, adjuvant chemotherapy (ACT) response, and immune milieu in different SCLC sub...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | MedComm |
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| Online Access: | https://doi.org/10.1002/mco2.370 |
| _version_ | 1797659154998886400 |
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| author | Chaoqiang Deng Yue Wang Fangqiu Fu Di Li Qiang Zheng Yan Jin Yuan Li Haiquan Chen Yang Zhang |
| author_facet | Chaoqiang Deng Yue Wang Fangqiu Fu Di Li Qiang Zheng Yan Jin Yuan Li Haiquan Chen Yang Zhang |
| author_sort | Chaoqiang Deng |
| collection | DOAJ |
| description | Abstract Despite recent progress in subtype classification for small cell lung carcinoma (SCLC), little is known about the biomarker for triple‐negative (ASCL1, NEUROD1, and POU2F3 negative) tumors. The long‐term survival, adjuvant chemotherapy (ACT) response, and immune milieu in different SCLC subtypes have also not been well established. Here, we retrospectively collected a large cohort of 192 primary SCLC tumors and reported that ASCL1‐, NEUROD1‐ and POU2F3‐dominant subtypes counted for 61.38%, 19.31%, and 6.21%, respectively. Subtype intra‐tumoral heterogeneity and co‐expression at the single‐cell level existed substantially. The expression of tumor‐derived Vimentin (VIM) was nearly restricted to triple‐negative SCLC tumors (15/19, 78.9%) while YAP1 expression was distributed widely in other subtypes. The SCLC subtyping model was independently prognostic of OS and RFS (p < 0.001 and p = 0.043). In particular, patients with ASCL1‐positive SCLC tumors can benefit more from ACT, and VIM‐positive tumors did the opposite. Compared with other subtypes, the VIM‐dominant SCLC subtype was associated with abundant but functionally impaired CD4+ and CD8+ T‐cells, which highly expressed inhibitory checkpoints and potentially benefit from PD‐L1 blockade therapy. Our study showed that tumor‐derived SCLC‐V subtype could independently predict ACT response. The distinct immune landscape between subtypes may help inform personalized immune therapeutic approaches. |
| first_indexed | 2024-03-11T18:09:47Z |
| format | Article |
| id | doaj.art-02e0a0ab71ae4615a33fd3f3194a6843 |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-03-11T18:09:47Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj.art-02e0a0ab71ae4615a33fd3f3194a68432023-10-16T15:20:40ZengWileyMedComm2688-26632023-10-0145n/an/a10.1002/mco2.370Tumor‐derived Vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and T‐cell‐inflamed phenotype in small cell lung cancerChaoqiang Deng0Yue Wang1Fangqiu Fu2Di Li3Qiang Zheng4Yan Jin5Yuan Li6Haiquan Chen7Yang Zhang8Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaInstitute of Thoracic Oncology Fudan University Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaInstitute of Thoracic Oncology Fudan University Shanghai ChinaInstitute of Thoracic Oncology Fudan University Shanghai ChinaInstitute of Thoracic Oncology Fudan University Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering Fudan University Shanghai Cancer Center Shanghai ChinaAbstract Despite recent progress in subtype classification for small cell lung carcinoma (SCLC), little is known about the biomarker for triple‐negative (ASCL1, NEUROD1, and POU2F3 negative) tumors. The long‐term survival, adjuvant chemotherapy (ACT) response, and immune milieu in different SCLC subtypes have also not been well established. Here, we retrospectively collected a large cohort of 192 primary SCLC tumors and reported that ASCL1‐, NEUROD1‐ and POU2F3‐dominant subtypes counted for 61.38%, 19.31%, and 6.21%, respectively. Subtype intra‐tumoral heterogeneity and co‐expression at the single‐cell level existed substantially. The expression of tumor‐derived Vimentin (VIM) was nearly restricted to triple‐negative SCLC tumors (15/19, 78.9%) while YAP1 expression was distributed widely in other subtypes. The SCLC subtyping model was independently prognostic of OS and RFS (p < 0.001 and p = 0.043). In particular, patients with ASCL1‐positive SCLC tumors can benefit more from ACT, and VIM‐positive tumors did the opposite. Compared with other subtypes, the VIM‐dominant SCLC subtype was associated with abundant but functionally impaired CD4+ and CD8+ T‐cells, which highly expressed inhibitory checkpoints and potentially benefit from PD‐L1 blockade therapy. Our study showed that tumor‐derived SCLC‐V subtype could independently predict ACT response. The distinct immune landscape between subtypes may help inform personalized immune therapeutic approaches.https://doi.org/10.1002/mco2.370chemotherapyimmune landscapelong‐term survivalmolecular subtypeSCLC |
| spellingShingle | Chaoqiang Deng Yue Wang Fangqiu Fu Di Li Qiang Zheng Yan Jin Yuan Li Haiquan Chen Yang Zhang Tumor‐derived Vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and T‐cell‐inflamed phenotype in small cell lung cancer MedComm chemotherapy immune landscape long‐term survival molecular subtype SCLC |
| title | Tumor‐derived Vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and T‐cell‐inflamed phenotype in small cell lung cancer |
| title_full | Tumor‐derived Vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and T‐cell‐inflamed phenotype in small cell lung cancer |
| title_fullStr | Tumor‐derived Vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and T‐cell‐inflamed phenotype in small cell lung cancer |
| title_full_unstemmed | Tumor‐derived Vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and T‐cell‐inflamed phenotype in small cell lung cancer |
| title_short | Tumor‐derived Vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and T‐cell‐inflamed phenotype in small cell lung cancer |
| title_sort | tumor derived vimentin as a novel biomarker for distinct subtypes predicting adjuvant chemotherapy resistance and t cell inflamed phenotype in small cell lung cancer |
| topic | chemotherapy immune landscape long‐term survival molecular subtype SCLC |
| url | https://doi.org/10.1002/mco2.370 |
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