Differential expression of the MYC‐Notch axis drives divergent responses to the front‐line therapy in central and peripheral extensive‐stage small‐cell lung cancer

Central and peripheral extensive-stage small-cell lung cancer (ES-SCLC) are reported to be two distinct tumor entities, but their responses to the front-line therapies and underlying biological mechanisms remain elusive. In this study, we first compared the outcomes of central and peripheral ES-SCLC receiving front-line chemotherapy or chemo-immunotherapy with a cohort of 265 patients. Then we performed single-cell RNA sequencing (scRNA-seq) on nine treatment-naïve ES-SCLC samples to investigate potential mechanisms underlying the response differences. Under chemotherapy, the peripheral type had a lower objective response rate (44.8% vs. 71.2%, <i>p </i>= 0.008) and shorter progression-free survival (median 3.4 vs. 5.1 months, <i>p </i>= 0.001) than the central type. When comparing chemo-immunotherapy with chemotherapy, the peripheral type showed a greater potential to reduce progression (HR, 0.18 and 0.52, respectively) and death (HR, 0.44 and 0.91 respectively) risks than the central type. Concerning the scRNA-seq data, the peripheral type was associated with chemo-resistant and immune-responsive tumoral and microenvironmental features, including a higher expression level of MYC-Notch-non-neuroendocrine (MYC-Notch-non-NE) axis and a more potent antigen presentation and immune activation status. Our results revealed that central and peripheral ES-SCLC had distinct responses to front-line treatments, potentially due to differential activation statuses of the MYC-Notch-non-NE axis.

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Publication Details

Journal
MedComm
Published
2025-02-18
DOI
https://doi.org/10.1002/mco2.70112
Citations
2
Primary Topic
Lung Cancer Research Studies
Type
article
Field-Weighted Citation Impact
2.09

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article

Differential expression of the MYC‐Notch axis drives divergent responses to the front‐line therapy in central and peripheral extensive‐stage small‐cell lung cancer

Fengying Wu, Luonan Chen, Guanghui Gao, Rui Xia et al.
2 citations
MedComm
Lung Cancer Research Studies
2.09
article

Differential expression of the MYC‐Notch axis drives divergent responses to the front‐line therapy in central and peripheral extensive‐stage small‐cell lung cancer

Fengying Wu, Luonan Chen, Guanghui Gao, Rui Xia, Caicun Zhou, Jingyun Shi, Shiqi Mao, Libo Luo, Lei Cheng, Wei Li, Qian Liu, Yan Wang, Xuefei Li, Chao Zhao, Tao Jiang, He Du, Jia Yu, Shuo Yang, Fei Zhou, Shengxiang Ren, Xiaoxia Chen
article en
2 citations

Abstract

Central and peripheral extensive-stage small-cell lung cancer (ES-SCLC) are reported to be two distinct tumor entities, but their responses to the front-line therapies and underlying biological mechanisms remain elusive. In this study, we first compared the outcomes of central and peripheral ES-SCLC receiving front-line chemotherapy or chemo-immunotherapy with a cohort of 265 patients. Then we performed single-cell RNA sequencing (scRNA-seq) on nine treatment-naïve ES-SCLC samples to investigate potential mechanisms underlying the response differences. Under chemotherapy, the peripheral type had a lower objective response rate (44.8% vs. 71.2%, <i>p </i>= 0.008) and shorter progression-free survival (median 3.4 vs. 5.1 months, <i>p </i>= 0.001) than the central type. When comparing chemo-immunotherapy with chemotherapy, the peripheral type showed a greater potential to reduce progression (HR, 0.18 and 0.52, respectively) and death (HR, 0.44 and 0.91 respectively) risks than the central type. Concerning the scRNA-seq data, the peripheral type was associated with chemo-resistant and immune-responsive tumoral and microenvironmental features, including a higher expression level of MYC-Notch-non-neuroendocrine (MYC-Notch-non-NE) axis and a more potent antigen presentation and immune activation status. Our results revealed that central and peripheral ES-SCLC had distinct responses to front-line treatments, potentially due to differential activation statuses of the MYC-Notch-non-NE axis.

MedCommVol. 6(3)
Tongji University (CN), Hubei University of Medicine (CN), Chinese Academy of Sciences (CN), Center for Excellence in Molecular Cell Science (CN), Shanghai Pulmonary Hospital (CN), University of Chinese Academy of Sciences (CN), Lac Courte Oreilles Ojibwe University (US)
National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, Science and Technology Commission of Shanghai Municipality, Natural Science Foundation of Hubei Province, Shanghai Shenkang Hospital Development Center, Shanghai Pulmonary Hospital, National Key Clinical Specialty Discipline Construction Program of China
Good health and well-being
Openalex Percentile: Top 14%
Lung Cancer Research Studies
2.09
DOIOpen Access PDFOpenAlex
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