Abstract
Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. Currently, a lack of serological biomarkers for early LC diagnosis is a major roadblock for early intervention and prevention of LC. To undertake this challenge, we employed a two-phase strategy to discover and validate a biomarker panel using a protein array-based approach. In Phase I, we obtained serological autoimmune profiles of 80 LC patients and 20 healthy subjects on HuProt arrays, and identified 170 candidate proteins significantly associated with LC. In Phase II, we constructed a LC focused array with the 170 proteins, and profiled a large cohort, comprised of 352 LC patients, 93 healthy individuals, and 101 patients with lung benign lesions (LBL). The comparison of autoimmune profiles between the early stage LC and the combined group of healthy and LBL allowed us to identify and validate a biomarker panel of p53, HRas, and ETHE1 for diagnosis of early stage LC with 50% sensitivity at >90% specificity. Finally, the performance of this biomarker panel was confirmed in ELISA tests. In summary, this study represents one of the most comprehensive proteome-wide surveys with one of the largest (i.e. 1,101 unique samples) and most diverse (i.e. nine disease groups) cohorts, resulting in a biomarker panel with good performance.
Highlights
Lung cancer (LC)1 remains the leading cause of mortality from malignant tumors worldwide [1, 2]
Regardless of the great advancements in targeted therapy and immunotherapy against LC in recent years, surgical resection followed by adjunctive radiation and/or chemotherapy is still the preferred method in the treatment of nonsmall-cell lung cancer (NSCLC) patients in early stages (e.g. I-II LC), and when surgery is performed, there is a 70% one-year survival rate if the diagnosis is made at the earliest stage [6]
100 serum samples collected from 80 LC patients and 20 healthy individuals, were individually profiled on human proteome (HuProt) arrays
Summary
Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide [1, 2]. High-resolution (or low-dose) computed tomography (CT) of the chest is the only screening test shown to be efficacious at reducing mortality from early stages of lung cancer (8 –10). As reported by the National Lung Screening Trial (NLST) of randomized 53,454 high-risk, asymptomatic adults, three rounds of annual screening with low-dose CT decreased LC mortality by 20% [8]. The discovery of noninvasive serological biomarkers for early stage LC diagnosis that yield high sensitivity and specificity will greatly benefit intervention and prevention of LC. We employed a protein array-based approach to comprehensively survey autoantibodies against the human proteome for identification of novel serological biomarkers for early diagnosis in LC. ELISA tests further demonstrated the potential of this biomarker panel in future clinical diagnostic test formats
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