Biomarkers in lung cancer screening: a narrative review

Abstract

Although when used as a lung cancer screening tool low-dose computed tomography (LDCT) has demonstrated a significant reduction in lung cancer related mortality, it is not without pitfalls. The associated high false positive rate, inability to distinguish between benign and malignant nodules, cumulative radiation exposure, and resulting patient anxiety have all demonstrated the need for adjunctive testing in lung cancer screening. Current research focuses on developing liquid biomarkers to complement imaging as non-invasive lung cancer diagnostics. Biomarkers can be useful for both the early detection and diagnosis of disease, thereby decreasing the number of unnecessary radiologic tests performed. Biomarkers can stratify cancer risk to further enrich the screening population and augment existing risk prediction. Finally, biomarkers can be used to distinguish benign from malignant nodules in lung cancer screening. While many biomarkers require further validation studies, several, including autoantibodies and blood protein profiling, are available for clinical use. This paper describes the need for biomarkers as a lung cancer screening tool, both in terms of diagnosis and risk assessment. Additionally, this paper will discuss the goals of biomarker use, describe properties of a good biomarker, and review several of the most promising biomarkers currently being studied including autoantibodies, complement fragments, microRNA, blood proteins, circulating tumor DNA (ctDNA), and DNA methylation. Finally, we will describe future directions in the field of biomarker development.

Combination Analysis of PCDHGA12 and CDO1 DNA Methylation in Bronchial Washing Fluid for Lung Cancer Diagnosis

“…This study did not combine with methylation of other DNAs known to be associated with lung cancer including SOX17, TAC1, HOXA7, and RASSF1A. 10 36 37 38 Lastly, in this study, a statistically significant increase in sensitivity was shown as the stage of the patients in the subgroup progressed, with 57.1% in stages I and II compared to 88% in stage III and IV of lung cancer. The sensitivity of this study increases as the stage progresses, however patients with advanced lung cancer require biopsy for chemotherapy rather than surgery.…”

The Role of Biomarkers in Lung Cancer Screening

“…Additionally, positive and negative predictive values are of equal importance; it is necessary to be able to discern those patients with a positive test who actually have the disease and those with a negative test who are truly disease-free [ 11 ]. The use of a risk-predictive biomarker for a disease with low prevalence requires a strong negative predictive value [ 12 ]. Furthermore, a clinically useful biomarker should be easily measurable, accurate, reproducible and inexpensive [ 13 ].…”

Smart Sensors and Microtechnologies in the Precision Medicine Approach against Lung Cancer

“…A neoplastic mass can be detected, at least at routine imaging screening, once it has reached a diameter of at least 0.5/1 cm [ 133 , 134 ]; however, noninvasive blood tests based on circulating tumor DNA and epigenetic traits can allow earlier diagnosis [ 135 , 136 , 137 ]. This approach has been widely implemented and validated for lung cancer as well for a review, see [ 138 , 139 , 140 , 141 , 142 ]. Notably, lung cancer marker detection can be more efficiently reached through the so-called semiconductor quantum dots (QDs), namely nanoparticles featuring stable and intense fluorescence which are now employed to expand the in vitro analysis of blood and tissue samples, as well as molecular imaging [ 143 ].…”