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MET inhibitors have shown promising efficacy for MET-dysregulated non-small cell lung cancer (NSCLC). However, quite a few patients cannot benefit from it due to the lack of powerful biomarkers. This study aims to explore the potential role of plasma proteomics-derived biomarkers for patients treated with MET inhibitors using mass spectrometry. We analyzed the plasma proteomics from patients with MET dysregulation (including MET amplification and MET overexpression) treated with MET inhibitors. Thirty-three MET-dysregulated NSCLC patients with longitudinal 89 plasma samples were included. We classified patients into the PD group and non-PD group based on clinical response. The baseline proteomic profiles of patients in the PD group were distinct from those in the non-PD group. Through protein screening, we found that a four-protein signature (MYH9, GNB1, ALOX12B, HSD17B4) could predict the efficacy of patients treated with MET inhibitors, with an area under the curve (AUC) of 0.93, better than conventional fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC) tests. In addition, combining the four-protein signature with FISH or IHC test could also reach higher predictive performance. Further, the combined signature could predict progression-free survival for MET-dysregulated NSCLC (p < 0.001). We also validated the performance of the four-protein signature in another cohort of plasma using an enzyme-linked immunosorbent assay. In conclusion, the four plasma protein signature (MYH9, GNB1, ALOX12B, and HSD17B4 proteins) might play a substitutable or complementary role to conventional MET FISH or IHC tests. This exploration will help select patients who may benefit from MET inhibitors.

Dissecting the functional diversity of T cells is critical in elucidating mechanisms and in developing therapies for various diseases. Here, we designed a 31-parameter (29-color) panel to enable the characterization of T-cell subsets and immunophenotyping of the human peripheral blood and lymph nodes using cell surface staining. In addition to adaptive T-cell markers, TCR Vα24-Jα18, TCR γδ, TCR Vɑ7.2, and CD161 were included to identify iNKT, γδ T, and MAIT cells, respectively, which are innate-like T cells. C-X-C chemokine receptors (CXCR3, CXCR4, CXCR5, CXCR6) and C-C motif chemokine receptors (CCR4, CCR6, CCR7) were included to enable the identification of Th cell subsets (Th1, Th2, Th17), Tfh cell subsets (Tfh1, Tfh2, Tfh17), and Th cells with specific homing capacities. Furthermore, in this panel, we also used markers for assessing cell differentiation (CD45RO, CD7), activation (CD57, CD95, HLA-DR) and the expression of some cosignaling molecules (PD-1, NKG2D, CD28). Particularly, CD69 and CD103 were included for the further analysis of tissue resident memory T (Trm) cells. This panel would enable the in-depth immunophenotyping of human T-cell subsets, and may be applied in the monitoring, prognosis, and mechanistic studies of various immune-related diseases.