Liquid Biopsy in Lung Cancer: Biomarkers for the Management of Recurrence and Metastasis.

Liquid biopsies have emerged as a promising tool for the detection of metastases as well as local and regional recurrence in lung cancer. Liquid biopsy tests involve analyzing a patient's blood, urine, or other body fluids for the detection of biomarkers, including circulating tumor cells or tumor-derived DNA/RNA that have been shed into the bloodstream. Studies have shown that liquid biopsies can detect lung cancer metastases with high accuracy and sensitivity, even before they are visible on imaging scans. Such tests are valuable for early intervention and personalized treatment, aiming to improve patient outcomes. Liquid biopsies are also minimally invasive compared to traditional tissue biopsies, which require the removal of a sample of the tumor for further analysis. This makes liquid biopsies a more convenient and less risky option for patients, particularly those who are not good candidates for invasive procedures due to other medical conditions. While liquid biopsies for lung cancer metastases and relapse are still being developed and validated, they hold great promise for improving the detection and treatment of this deadly disease. Herein, we summarize available and novel approaches to liquid biopsy tests for lung cancer metastases and recurrence detection and describe their applications in clinical practice.

Typical Lung Carcinoids with Metastasis: Potential Role of MicroRNAs in the Regulation of Adaptive Immunity Associated with Disease: a Case Study.

BACKGROUND/AIMS: Lung carcinoids are uncommon neuroendocrine tumours. Molecular features of lung carcinoids have been poorly defined. microRNAs (miRNAs) are potent gene expression regulators with important roles in cancer development and progression. However, little is known on the role of miRNAs in the pathogenesis of lung carcinoids. Our goals were to identify commonly deregulated miRNAs in a rare case of lung carcinoid of typical histology with metastasis, as well as map miRNA target genes in pathways potentially associated with disease development and progression. METHODS: miRNA expression profiles were assessed using the TaqMan Low Density Arrays, which is a platform including 384 miRNAs. miRNA profiles were generated in the tumor and its corresponding lymph node metastasis, compared to reference normal lung tissues. Furthermore, miRNA expression was validated in a separate, publicly available external dataset (n=19 typical lung carcinoids; 2/19 were metastatic tumors, compared to six normal lung tissues, GSE77380). Following this analysis, computational tools were applied for data interpretation. miRTarBase was used to determine miRNA-target genes, followed by ToppGene Suite analysis to identify pathways and biological functions. In addition, the expression of genes targeted by miRNAs was validated in a second, separate external dataset (n=13 tumour samples, GSE35679). GEO2R data analysis tool was used in both validation analyses (miRNAs and genes). RESULTS: We identified 15 commonly significantly downregulated miRNAs (fold change, FC≥2 and p<0.05) in the tumour and its paired metastasis, with further decreasing levels in the metastatic lesion. Downregulation of miR-126-3p and miR-146b-5p was validated in the external dataset GSE77380. In addition, SOX2 and TCF4 genes, targeted by miR-126-3p, were consistently overexpressed in a subset of six typical lung carcinoids from the external dataset GSE35679. Pathways analysis showed that miRNAs miR-126-3p and miR-146b-5p target genes with a role in the regulation of adaptive immune response. CONCLUSION: Our results contribute to the identification of miRNA expression changes in a typical lung carcinoid and its corresponding lymph node metastasis. Down-regulated levels of miR-126-3p and miR-146b-5p and target gene over-expression could play a role in the progression of this case of primary typical lung carcinoid to regional metastasis. Identified miRNAs and target genes are potential candidates for validation in a larger number of cases.

Advances in the Molecular Landscape of Lung Cancer Brain Metastasis.

Lung cancer is one of the most frequent tumors that metastasize to the brain. Brain metastasis (BM) is common in advanced cases, being the major cause of patient morbidity and mortality. BMs are thought to arise via the seeding of circulating tumor cells into the brain microvasculature. In brain tissue, the interaction with immune cells promotes a microenvironment favorable to the growth of cancer cells. Despite multimodal treatments and advances in systemic therapies, lung cancer patients still have poor prognoses. Therefore, there is an urgent need to identify the molecular drivers of BM and clinically applicable biomarkers in order to improve disease outcomes and patient survival. The goal of this review is to summarize the current state of knowledge on the mechanisms of the metastatic spread of lung cancer to the brain and how the metastatic spread is influenced by the brain microenvironment, and to elucidate the molecular determinants of brain metastasis regarding the role of genomic and transcriptomic changes, including coding and non-coding RNAs. We also present an overview of the current therapeutics and novel treatment strategies for patients diagnosed with BM from NSCLC.