1. A Predictive 7-Gene Assay and Prognostic Protein Biomarkers for Non-small Cell Lung Cancer
- Author
-
Guoan Chen, Ujala Bokhary, Afshin Dowlati, Chunlin Dong, John A. Howington, Justine Shaffer, Yong Qian, Rebecca Raese, Thomas A. Hensing, David G. Beer, Nancy Lan Guo, Lin Liu, and Salvi Singh
- Subjects
Male ,0301 basic medicine ,Oncology ,Microarray ,medicine.medical_treatment ,non-small cell lung cancer (NSCLC) ,lcsh:Medicine ,Kaplan-Meier Estimate ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Oligonucleotide Array Sequence Analysis ,lcsh:R5-920 ,Hazard ratio ,General Medicine ,Middle Aged ,Prognosis ,3. Good health ,Gene Expression Regulation, Neoplastic ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Prognostic protein biomarkers ,Female ,Immunotherapy ,lcsh:Medicine (General) ,Research Paper ,Adult ,medicine.medical_specialty ,DNA Copy Number Variations ,Predictive gene assay ,Non-small cell lung cancer (NSCLC) ,Disease-Free Survival ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Chemotherapy ,Lung cancer ,Gene ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Precision therapy ,business.industry ,lcsh:R ,medicine.disease ,Clinical trial ,030104 developmental biology ,business - Abstract
Purpose This study aims to develop a multi-gene assay predictive of the clinical benefits of chemotherapy in non-small cell lung cancer (NSCLC) patients, and substantiate their protein expression as potential therapeutic targets. Patients and methods The mRNA expression of 160 genes identified from microarray was analyzed in qRT-PCR assays of independent 337 snap-frozen NSCLC tumors to develop a predictive signature. A clinical trial JBR.10 was included in the validation. Hazard ratio was used to select genes, and decision-trees were used to construct the predictive model. Protein expression was quantified with AQUA in 500 FFPE NSCLC samples. Results A 7-gene signature was identified from training cohort (n = 83) with accurate patient stratification (P = 0.0043) and was validated in independent patient cohorts (n = 248, P, Highlights • This paper develops a RT-PCR based 7-gene assay to predict the clinical benefits of chemotherapy for precision oncology • This work discovers a prognostic protein biomarker ZNF71 using AQUA technique as a potential companion test and therapeutic target • This research identifies prognostic mRNA and protein biomarker CD27 with implications in immunotherapy The results from this paper will help clinicians to select NSCLC patients who might benefit from chemotherapy. The identified prognostic protein biomarkers might also be new therapeutic targets in chemotherapy and immunotherapy.
- Published
- 2018