Circulating Biomarkers for Early Stage Non-Small Cell Lung Carcinoma Detection: Supplementation to Low‐Dose Computed Tomography

Abstract

Lung cancer is currently the leading cause of cancer death in both developing and developed countries. Given that lung cancer has poor prognosis in later stages, it is essential to achieve an early diagnosis to maximize patients’ overall survival. Non-small cell lung cancer (NSCLC) is the most common form of primary lung cancer in both smokers and non-smokers. The current standard screening method, low‐dose computed tomography (LDCT), is the only radiological method that demonstrates to have mortality benefits across multiple large randomized clinical trials (RCT). However, these RCTs also found LDCT to have a significant false positive rate that results in unnecessary invasive biopsies being performed. Due to the lack of both sensitive and specific screening methods for the early detection of lung cancer, there is an urgent need for alternative minimally or non-invasive biomarkers that may provide diagnostic, and/or prognostic information. This has led to the identification of circulating biomarkers that can be readily detectable in blood and have been extensively studied as prognosis markers. Circulating microRNA (miRNA) in particular has been investigated for these purposes as an augmentation to LDCT, or as direct diagnosis of lung cancer. There is, however, a lack of consensus across the studies on which miRNAs are the most clinically useful. Besides miRNA, other potential circulating biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNAs) and non-coding RNAs (ncRNAs). In this review, we provide the current outlook of several of these biomarkers for the early diagnosis of NSCLC.

Computational Analyses of YY1 and Its Target RKIP Reveal Their Diagnostic and Prognostic Roles in Lung Cancer

“…Although several biomarkers have been suggested for the diagnosis and prognosis of LC, in the era of precision medicine, there is still a need to identify “tailored markers” that can be proposed in clinical setting for early diagnosis, prognosis and targeted therapy [ 19 ]. Additionally, it would be beneficial to identify diagnostic biomarkers able to optimize the current LDCT protocols, allowing, for example, the identification of the false positives, as well as the stratification of CT-positive subjects [ 20 , 21 ]. Among the challenges currently faced by research on LC biomarker development, there is the need for a deeper knowledge of lung carcinogenesis at both molecular and cellular levels.…”

MicroRNA, mRNA, and Proteomics Biomarkers and Therapeutic Targets for Improving Lung Cancer Treatment Outcomes

“…MiRNAs have emerged as important diagnostic and prognostic biomarkers and therapeutic targets in cancer treatment due to their functional involvement in gene and protein regulation and intracellular signaling [ 52 , 53 ]. MiRNA biomarkers are promising for the early detection of NSCLC supplementing low-dose CT screening [ 54 ] and the prognosis of advanced NSCLC patients treated with immunotherapy [ 55 ].…”

Emerging Roles and Mechanisms of lncRNA FOXD3-AS1 in Human Diseases

“…Indeed, NSCLC has a high mortality rate, and the 5-year survival rate of these patients remain challenging (54)(55)(56)(57). Despite advancements in early detection and treatment of NSCLC, the identification of molecular markers associated with patient survival is still necessary (53,(58)(59)(60). Multiple studies have demonstrated that FOXD3-AS1 is overexpressed in NSCLC tissues and cell lines (H1299, A549 and SPC-A1 cells) (24,(26)(27)(28).…”