We also report that RANK is frequently and highly expressed on primary human lung tumors and that a molecular signature of high RANKL and high RANK expression and low expression of OPG and LGR4, the natural endogenous inhibitors of the RANKL/RANK pathway, is associated with worse prognosis for lung cancer patients, in particular females, mirroring our genetic mouse data. Here, LGR4 is linked to lung cancer.