Thread by @LM_Orre

Very happy to present our #proteomics analysis of #lungcancer published today @NatureCancer!🙂
Here’s a walk-through: #MassSpec analysis covering almost 14k proteins in 141 NSCLC tumors revealed 6 proteome subtypes with distinct biology. 1/6
rdcu.be/cBOtU

#NSCLC proteome subtypes are driven by histology, growth pattern, immune cell infiltration, driver mutations, oncogenic pathways, and cell types, suggesting potential clinical value for treatment stratification and #PrecisionMedicine. 2/6

Unexpectedly, #proteogenomics analysis revealed that high neoantigen burden was linked to global hypomethylation, and that complex neoantigens mapping to genomic regions normally not active in lung were produced in immune-cold subtypes. 3/6

Immune evasion in one immune-cold subtype was linked to STK11 inactivation through an HNF1A-driven liver-specific transcriptional program resulting in expression of FGL1, a secreted ligand to the inhibitory T-cell receptor LAG3. #Immunotherapy. 4/6

Finally, we present a DIA MS and #ML-based NSCLC subtype classification pipeline, validate it in an independent cohort of 208 NSCLC cases and, in a first POC study, demonstrate the clinical applicability of the method by analyzing 84 biopsy samples from inoperable NSCLC. 5/6

Many thanks to all funders and contributing authors @lehtiolab, @karolinskainst, @scilifelab, @Lundsuni, @Oslounivsykehus and @EdinburghUni. If you want to learn more, you can also watch a video of me presenting the findings at the ICAP 2021 meeting!🤓 6/6