当前位置：
X-MOL 学术
›
Clin. Cancer Res.
›
论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Spatially preserved multi-region transcriptomic subtyping and biomarkers of chemoimmunotherapy outcome in extensive-stage small cell lung cancer
Clinical Cancer Research ( IF 11.5 ) Pub Date : 2024-04-17 , DOI: 10.1158/1078-0432.ccr-24-0104 Melina Peressini 1 , Rosario Garcia-Campelo 2 , Bartomeu Massuti 3 , Cristina Marti 4 , Manuel Cobo 5 , Vanesa Gutiérrez 6 , Manuel Dómine 7 , Jose Fuentes 8 , Margarita Majem 9 , Javier de Castro 10 , Juan Felipe Cordoba 11 , Maria Pilar Diz 12 , Dolores Isla 13 , Emilio Esteban 14 , Enric Carcereny 15 , Laia Vila 16 , Alberto Moreno-Vega 17 , Silverio Ros 18 , Amaia Moreno 19 , Francisco Javier Garcia 20 , Gerardo Huidobro 21 , Carlos Aguado 22 , Victor Cebey-Lopez 23 , Javier Valdivia 24 , Ramon Palmero 25 , Pilar Lianes 26 , Marta Lopez-Brea 27 , Oscar Juan. Vidal 28 , Mariano Provencio 29 , Edurne Arriola 30 , Javier Baena 31 , Mercedes Herrera 32 , Helena Bote 33 , Magdalena Molero 1 , Vera Adradas 1 , Santiago Ponce-Aix 34 , Angel Nuñez-Buiza 35 , Álvaro Ucero 1 , Susana Hernandez 36 , Fernando Lopez-Rios 33 , Esther Conde 33 , Luis Paz-Ares 31 , Jon Zugazagoitia 31
Clinical Cancer Research ( IF 11.5 ) Pub Date : 2024-04-17 , DOI: 10.1158/1078-0432.ccr-24-0104 Melina Peressini 1 , Rosario Garcia-Campelo 2 , Bartomeu Massuti 3 , Cristina Marti 4 , Manuel Cobo 5 , Vanesa Gutiérrez 6 , Manuel Dómine 7 , Jose Fuentes 8 , Margarita Majem 9 , Javier de Castro 10 , Juan Felipe Cordoba 11 , Maria Pilar Diz 12 , Dolores Isla 13 , Emilio Esteban 14 , Enric Carcereny 15 , Laia Vila 16 , Alberto Moreno-Vega 17 , Silverio Ros 18 , Amaia Moreno 19 , Francisco Javier Garcia 20 , Gerardo Huidobro 21 , Carlos Aguado 22 , Victor Cebey-Lopez 23 , Javier Valdivia 24 , Ramon Palmero 25 , Pilar Lianes 26 , Marta Lopez-Brea 27 , Oscar Juan. Vidal 28 , Mariano Provencio 29 , Edurne Arriola 30 , Javier Baena 31 , Mercedes Herrera 32 , Helena Bote 33 , Magdalena Molero 1 , Vera Adradas 1 , Santiago Ponce-Aix 34 , Angel Nuñez-Buiza 35 , Álvaro Ucero 1 , Susana Hernandez 36 , Fernando Lopez-Rios 33 , Esther Conde 33 , Luis Paz-Ares 31 , Jon Zugazagoitia 31
Affiliation
Background: Transcriptomic subtyping holds promise for personalized therapy in extensive-stage small-cell lung cancer (ES-SCLC). In this study, we aimed to assess intratumoral transcriptomic subtype diversity and to identify biomarkers of long-term chemoimmunotherapy benefit in human ES-SCLC. Patients and methods: We analyzed tumor samples from 58 ES-SCLC patients enrolled in two multicenter single-arm phase IIIb studies evaluating front-line chemoimmunotherapy in Spain: n=32 from the IMfirst trial, and n=26 from the CANTABRICO trial. We utilized the GeoMxTM DSP system to perform multi-region transcriptomic analysis. For subtype classification, we performed hierarchical clustering using the relative expression of ASCL1 (SCLC-A), NEUROD1 (SCLC-N), POU2F3 (SCLC-P), and YAP1 (SCLC-Y). Results: Subtype distribution was similar between both cohorts, except for SCLC-P, not identified in the CANTABRICO_DSP cohort. A total of 44% of the patients in both cohorts had tumors with multiple co-existing transcriptional subtypes. Transcriptional subtypes or subtype heterogeneity were not associated with outcomes. Most potential targets did not show subtype-specific expression. Consistently in both cohorts, tumors from patients with long-term benefit (time to progression ³12 months) contained an IFNg-dominated mRNA profile, including enhanced capacity for antigen presentation. Hypoxia and glycolytic pathways were associated with resistance to chemoimmunotherapy. Conclusions: This work suggests that intratumoral heterogeneity, inconsistent association with outcome, and unclear subtype-specific target expression might be significant challenges for subtype-based precision oncology in SCLC. Pre-existing IFNg-driven immunity and mitochondrial metabolism seem correlates of long-term efficacy in this study, although the absence of a chemotherapy control arm precludes concluding that these are predictive features specific for immunotherapy.
更新日期：2024-04-17
京公网安备 11010802027423号