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Poster Presentations
02. Tumor microenvironment and microbiome in immunotherapy
P02.06 Integrated multi-omics unraveled a basal cell-dependent signature predictor of outcome and immunotherapy response in LUSC
  1. J Jia1,
  2. R Liu2,
  3. B Deng1,
  4. X Guo3,
  5. L Trassl1,
  6. GA Giotopoulou1,
  7. SJ Behrend1,
  8. Y Liu4,
  9. AÖ Yildirim1,
  10. GT Stathopoulos1,
  11. AC Schamberger1 and
  12. IE Fernandez1
  1. 1Comprehensive Pneumology Center (CPC), Institute of Lung Health and Immunity (LHI), Helmholtz Zentrum München, Munich, Germany and Member of the German Center for Lung Research (DZL), Gießen, Germany, München, Germany
  2. 2Xi’an Jiaotong University, Xi’an, China
  3. 3Dalian Medical University, Dalian, China
  4. 4Shandong University, Jinan, China

Abstract

Background Lung squamous carcinoma (LUSC) is a major lung cancer killer with no biomarkers and limited therapeutic options. Although still unclear, transformation of the pseudostratified and basal epithelium is linked with its origin.

Materials and Methods With integrated transcriptomics, proteomics, genomics, epigenetics, and single-cell RNA sequencing (scRNA-seq), we explore basal cell-dependent signatures as therapy response predictors in LUSC.

Results Unsupervised clustering of the TCGA-LUSC cohort classified patients into ‘Basalimmune-high’ and ‘Basalimmune-low’ using immune and basal cell-associated hub genes. The ‘Basalimmune-high’ cluster had higher immune scores, immune cell infiltration (ICI), and better immunotherapy response. The ‘Basalimmune-low’ cluster had a higher proliferative basal cell enrichment score and higher expression of KRT5/6 and TP63. Both clusters had a unique and distinctive mutational landscape (shared driver mutations: TP53, KRTAP-5-5; Basalimmune-high: NOTCH1, ZFR; Basalimmune-low: ARID1A, RECQL5). Copy number variants results showed that both clusters had shared amplifications and deletions, but also individual ones [amplification - Basalimmune-high: WHSC1L1, KAT6A; Basalimmune-low: EGFR, AKT1); deletion - Basalimmune-high: ROBO1, FHIT; Basalimmune-low: STK11)]. 15 key prognostic genes were identified, and for the first time, CTTNBP2 and COL22A1 predicted survival in 4 different LUSC cohorts. Intercellular communication analysis of scRNA-seq showed a novel communication dependency between basal and immune cells that might influence immunotherapy response.

Conclusions For the first time, our multi-omic integrative approach identified ‘Basalimmune-high’ and ‘Basalimmune-low’ clusters that differ substantially in their genetic landscape, a 15 key prognostic gene signature that reflect survival, and a basal cell-dependent communication that predicts immunotherapy response in LUSC.

J. Jia: None. R. Liu: None. B. Deng: None. X. Guo: None. L. Trassl: None. G.A. Giotopoulou: None. S.J. Behrend: None. Y. Liu: None. A.Ö. Yildirim: None. G.T. Stathopoulos: None. A.C. Schamberger: None. I.E. Fernandez: None.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jitc-2024-ITOC10.25

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