Proteogenomic Prognosis

Lung cancer remains the leading cause of death in cancer patients worldwide (1). Could advanced analytical investigations change the status quo? A recent study subjected 87 lung adenocarcinoma (LUAD) tumors to a plethora of techniques, including whole-genome sequencing, transcriptome sequencing, mass spectrometry-led proteomics and phosphoproteomics, and reverse-phase protein arrays (2). The multi-pronged approach led to the discovery of three distinct forms of LUAD – a transition-high subtype linked to non-smokers, a transversion-high subtype linked with current smokers, and a structurally altered subtype linked to former smokers and characterized by TP53 alterations and genome-wide structural alterations. 

The researchers also identified that protein expression and groups of RNA within sample tumors were linked to cell immunity and concentration of cancer cells within tissue. The team was then able to identify and validate the expression signatures of RNA and proteins and establish their association with patient survival.

When the tumor subtypes were compared by outcome, the team saw that expression and histological subtypes were strongly associated with metastasis-free survival (MFS). Meanwhile, somatic genome signature subtypes were not linked with overall or MFS. The paper suggests that the biological factors of LUAD recorded in the proteomic approach hold a determining effect on MFS.

Finally, the authors of the paper highlighted how a detailed understanding of th e different molecular subtypes of LUAD could lead to therapy pathways designed to halt the development in pre-cancerous and early-stage LUAD tumors.