Combing proteomics with the long standing success of genomics, the new initiative of large-scale tissue proteogenomics demonstrated discovery to reveal new molecular subtypes of cancer in recent years. The different genetic background and environmental factors contribute to unique features of cancers in diversity of population, awaiting full delineation of genomic-to-proteomic network to identify the fundamental drivers and underlying mechanism. With the aim of accelerating the progress toward prevention, control and treatment for cancer, Taiwan joined the global effort of International Cancer Proteogenome Consortium (ICPC) to apply proteogenomics as a precision approach to delineate the connection of genomic abnormalities and protein alteration in individual cancer patient, which subsequently stimulates academia-government-industry collaboration to jointly map the pathway for next generation precision medicine for Taiwan/Asia cohort.
On the pilot study of early stage and never smoking lung adenocarcinoma (LUAD), the genomic landscape confirmed the distinct mutational profile of our cohort compared to previously reported studies. We observed gender-specific differences in driver and passenger mutations, which likely contribute to the disease heterogeneity and different clinical outcomes. We discovered mutation signatures predominantly associated with carcinogen as well as early onset females. Proteome subtypes highlight molecular differences that extend the classification beyond the level of clinical staging and genomic driver mutation, which signatures may provide clues on patient outcome and progression. Proteomics landscape also revealed the stage-specific progression signatures characterized by dramatic molecular reorganization at early stage to regulate cancer cell survival, migration and proliferation. Further validations by retrospective cohort not only supported the new molecular staging but also nominated biomarker candidates associated with the poor overall survival in patients. In summary, the integrated proteogenomics profile may provide molecular map for next generation precision medicine to address the unmet clinical need of NSCLC in Taiwan/Asia.