In-depth proteomic analyses reveal unique subtype-specific signatures in small cell lung cancer (part I: cell pellets)

Small-cell lung cancer (SCLC) represents about 13–15% of all lung cancers and with a five-year survival rate of less than 7%, it remains one of the most lethal forms of malignant diseases. It has a very aggressive course and is characterized by extensive chromosomal rearrangements, high mutation burden, and almost universal inactivation of the tumor suppressor genes TP53 and RB1. Therefore, the vast majority of SCLC patients are diagnosed with extensive-stage disease when surgery is not feasible and the treatment options are mostly limited to cytotoxic chemotherapy (CHT) and radiation. Importantly, targeted therapies for these patients have so far failed, and the success of immunotherapy in non-SCLC (NSCLC) has not been reflected in SCLC. Although SCLC has been formerly considered as a homogeneous disease with a single morphological type, recent advances in SCLC research have led to the development of subtype-specific classifications primarily based on neuroendocrine (NE) features and unique molecular profiles. Here, we investigate the general cell line characteristics on protein level, the relationship between the RNA-based classification and the protein expression profile, and the distinct biological processes specific for each subtype.