Lung cancer remains the leading cause of cancer-related deaths in the world, and non-small cell lung cancer (NSCLC) accounts for 84% of lung cancer cases and almost 80% of lung cancer deaths. … There are currently no effective biomarkers to select chemotherapy, immunotherapy, and radiotherapy for treating lung cancer patients. Novel therapeutic strategies are needed to combat this deadly disease. Our previous study developed a 7-gene assay for NSCLC prognosis and prediction of chemotherapeutic benefits. The ability of this gene assay to identify those at high risk for recurrence or metastasis would potentially inform the selection of specific adjuvant chemotherapy for these patients. Multiple identified genes were associated with chemoresponse and radiotherapy response in NSCLC. Included in this 7-gene assay, CD27 and ZNF71 had concordant mRNA and protein expression in NSCLC tumors. Our recent study showed that ZNF71-KRAB, the KRAB isoform that is transcriptional repression, was associated with epithelial-to-mesenchymal transition (EMT) in NSCLC tumors and cell lines. CD27, an emerging immune-checkpoint inhibitor, is being tested as adjuvant therapy in phase I/II clinical trials for multiple tumor types with promising results. These biomarkers have the potential to select chemotherapy, immunotherapy, and radiotherapy in combination with patient demographic, clinical, pathological, and comorbid characteristics using the prognostic model we developed (http://www.personalizedrx.org/) to achieve the goals of precision oncology.