CXCL1 and CXCL8: Reliable and feasible biomarkers differentiating intrapulmonary metastasis from multiple primary neoplasms in non-small cell lung cancers

ObjectiveIn NSCLC, the main approach to differentiate between intrapulmonary metastases (IPM) and multiple primary lung cancer (MPLC) is to integrate histopathological and genomic information. Here, we identified viable biomarkers that can distinguish IPM from MPLC by integrating comprehensive genomic profiling (CGP) and targeted RNA sequencing.MethodsWe retrospectively collected tissues from at least two lesions in 34 patients. 29 and 5 out of 34 patients determined as pathologic MPLC (pMPLC) and pathologic IPM, respectively, according to Martini-Melamed criteria (M-M criteria). A comprehensive investigation at genomic and transcriptomic level was conducted.ResultsNine of the 29 pMPLCs shared trunk mutations in their lesions and were consequently reclassified as IPM. Survival analyses revealed that classification integrated M-M criteria and mutational profiling could distinguish IPM/MPLC more accurately. Further exploration at the transcriptomic level revealed elevated expression levels of genes related to epithelial-mesenchymal transition and immunomodulatory pathways in IPM. Notably, the expression of <i>CXCL1</i> and <i>CXCL8</i> was significantly upregulated in IPM.ConclusionsWe found that the expression of <i>CXCL1</i> and <i>CXCL8</i> in any tumor lesion within a patient could reliably indicate IPM. Additionally, assessing the transcriptional levels of <i>CXCL1</i> and <i>CXCL8</i> also provide a dependable and practical approach to identify IPM from MPLC.