Proteomic profiling reveals the significance of lipid metabolism in small cell lung cancer recurrence and metastasis

Small cell lung cancer (SCLC) is a lethal and recalcitrant malignancy with early metastases. However, the molecular and cellular mechanisms underlying its aggressive characteristics remain relatively elusive. In this study, we conducted a comprehensive proteomic analysis of 90 primary tumors, 15 patient-matched lymph node metastatic tumors, and 15 brain metastatic tumors derived from a cohort of 105 SCLC patients. The potential mechanism for SCLC metastasis was investigated based on the variety of protein expression profiles. Primary tumors were divided into two categories according to the their different protein expression profiles, using metastatic tumors as reference. Proteomic comparisons across different groups revealed that lipid metabolism, especially phospholipid metabolism, and immune response had a critical role in SCLC metastasis. Additionally, it was shown that high- and low-density lipoprotein cholesterol were both independent prognostic factors for disease free survival of SCLC patients. To identify critical regulators of metastasis in SCLC, support vector machine was adopted to generate a biomarker combination of ten proteins, all of which significantly correlated with the infiltration of immune cells. Furthermore, it was demonstrated that high expression of phospholipase A2 group IIA in stroma was associated with delayed disease recurrence in limited stage SCLC. This study highlighted the critical significance of lipid metabolism, especially phospholipid metabolism in the disease recurrence and metastasis of SCLC.