Blood-Based Biomarker Panel for Personalized Lung Cancer Risk Assessment

Abstract

PURPOSE To investigate whether a panel of circulating protein biomarkers would improve risk assessment for lung cancer screening in combination with a risk model on the basis of participant characteristics. METHODS A blinded validation study was performed using prostate lung colorectal ovarian (PLCO) Cancer Screening Trial data and biospecimens to evaluate the performance of a four-marker protein panel (4MP) consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in combination with a lung cancer risk prediction model (PLCOm2012) compared with current US Preventive Services Task Force (USPSTF) screening criteria. The 4MP was assayed in 1,299 sera collected preceding lung cancer diagnosis and 8,709 noncase sera. RESULTS The 4MP alone yielded an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.77 to 0.82) for case sera collected within 1-year preceding diagnosis and 0.74 (95% CI, 0.72 to 0.76) among the entire specimen set. The combined 4MP + PLCOm2012 model yielded an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.82 to 0.88) for case sera collected within 1 year preceding diagnosis. The benefit of the 4MP in the combined model resulted from improvement in sensitivity at high specificity. Compared with the USPSTF2021 criteria, the combined 4MP + PLCOm2012 model exhibited statistically significant improvements in sensitivity and specificity. Among PLCO participants with ≥ 10 smoking pack-years, the 4MP + PLCOm2012 model would have identified for annual screening 9.2% more lung cancer cases and would have reduced referral by 13.7% among noncases compared with USPSTF2021 criteria. CONCLUSION A blood-based biomarker panel in combination with PLCOm2012 significantly improves lung cancer risk assessment for lung cancer screening.

The Blood Proteome of Imminent Lung Cancer Diagnosis

“…Encouragingly, this also implies that the markers have potential to improve short-term lung cancer risk prediction beyond existing risk calculators that leverage detailed information from smoking history. 33,34,50…”

“…Encouragingly, this also implies that the markers have potential to improve short-term lung cancer risk prediction beyond existing risk calculators that leverage detailed information from smoking history. 33,34,50 To better understand the relationships between the 36 markers, we conducted a sparse graphical LASSO-based network analysis and observed specific associations between 12 proteins among cases that did not appear among controls. These case-specific protein connections were clustered in three groups and were all broadly implicated in an extracellular defense response to somatic stress.…”

A Comprehensive Search of Non-Canonical Proteins in Non-Small Cell Lung Cancer and Their Impact on the Immune Response

“…Moreover, the ability to detect Ig-bound cryptoproteins in pre-diagnostic plasmas provides the potential that these may be sensitive and specific markers of lung cancer risk and presence of disease. These could either serve to complement to existing markers [ 31 , 32 , 33 ] or may offer sufficient performance to stand alone as a new source of biomarkers for lung cancer early detection or risk assessment. Future studies, exploring the utility of autoantibodies directed against cancer-associated cryptoproteins alone or in combination with other biomarker types for risk prediction of lung cancer, are warranted.…”

Lung cancer susceptibility beyond smoking history: opportunities and challenges

“…Lung cancer risk models that include genetic predisposition as well as other types of biomarkers have the potential to increase the effectiveness of lung cancer screening. A case in point is the recent validation of a biomarker panel based on four proteins ( 16 ). This blinded validation study was performed in combination with a lung cancer risk prediction model based on subject characteristics, using prostate lung colorectal ovarian (PLCO) Cancer Screening Trial data.…”