By using the GWAS approach, we have previously identified several genetic variants located on 4q12 that were significantly associated with PFS of patients with lung adenocarcinoma (ADC) receiving first-line EGFR-TKI therapy. Intriguingly, we found those genetic variants were significantly associated with expression level of NMU , which is known to be upregulated in lung ADC and significantly associated with patients' worse poor survival. Here we found that knockdown of NMU expression remarkedly suppressed lung ADC cell proliferation in vitro and xenograft tumor growth in mice model, while forced expression of NMU had exactly the opposite effects. Also, based on xenograft model of lung ADC in mice, we further found that NMU not only can promote cancer cell growth via autocrine effect, but also can affect other cell types, e.g., fibroblast cells via paracrine effect, to foster a pro-tumor milieu by providing survival advantages to cancer cells. Our findings may lead to innovation of novel biomarkers for stratification of patients for precision medicine of lung cancer (LC) and invention of new therapeutic agents that may benefit LC patients by improving their survival and prognosis.
