Defining the landscape of circRNAs in non-small cell lung cancer and their potential as liquid biopsy biomarkers: a complete review including current methods.

Despite the significant decrease in population-level mortality of lung cancer patients as reflected in the Surveillance Epidemiology and End Results program national database, lung cancer, with non-small cell lung cancer (NSCLC) in the lead, continues to be the most commonly diagnosed cancer and foremost cause of cancer-related death worldwide, primarily due to late-stage diagnosis and ineffective treatment regimens. Although innovative single therapies and their combinations are constantly being tested in clinical trials, the five-year survival rate of late-stage lung cancer remains only 5% (Cancer Research, UK). Henceforth, investigation in the early diagnosis of lung cancer and prediction of treatment response is critical for improving the overall survival of these patients. Circular RNAs (circRNAs) are a re-discovered type of RNAs featuring stable structure and high tissue-specific expression. Evidence has revealed that aberrant circRNA expression plays an important role in carcinogenesis and tumor progression. Further investigation is warranted to assess the value of EV- and platelet-derived circRNAs as liquid biopsy-based readouts for lung cancer detection. This review discusses the origin and biology of circRNAs, and analyzes their present landscape in NSCLC, focusing on liquid biopsies to illustrate the different methodological trends currently available in research. The possible limitations that could be holding back the clinical implementation of circRNAs are also analyzed.