Deciphering the Molecular Profile of Lung Cancer: New Strategies for the Early Detection and Prognostic Stratification

Dama, Elisa; Melocchi, Valentina; Colangelo, Tommaso; Cuttano, Roberto; Bianchi, Fabrizio

doi:10.3390/jcm8010108

Cited by 8 publications

(8 citation statements)

References 98 publications

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“…Nowadays, the advent of more sophisticated and precise bioinformatic tools and computational approaches has sped up the identification of novel diagnostic and prognostic cancer biomarkers, either focused on proteins, coding transcripts, epigenome modifications or non-coding transcripts [ 14 , 15 ]. In lung cancer, in particular, the differential expression of miRNAs allowed the development of innovative and promising cancer biomarkers [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas

Dama

Melocchi

Mazzarelli

et al. 2020

ncRNA

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Lung cancer burden can be reduced by adopting primary and secondary prevention strategies such as anti-smoking campaigns and low-dose CT screening for high risk subjects (aged >50 and smokers >30 packs/year). Recent CT screening trials demonstrated a stage-shift towards earlier stage lung cancer and reduction of mortality (~20%). However, a sizable fraction of patients (30–50%) with early stage disease still experience relapse and an adverse prognosis. Thus, the identification of effective prognostic biomarkers in stage I lung cancer is nowadays paramount. Here, we applied a multi-tiered approach relying on coupled RNA-seq and miRNA-seq data analysis of a large cohort of lung cancer patients (TCGA-LUAD, n = 510), which enabled us to identify prognostic miRNA signatures in stage I lung adenocarcinoma. Such signatures showed high accuracy (AUC ranging between 0.79 and 0.85) in scoring aggressive disease. Importantly, using a network-based approach we rewired miRNA-mRNA regulatory networks, identifying a minimal signature of 7 miRNAs, which was validated in a cohort of FFPE lung adenocarcinoma samples (CSS, n = 44) and controls a variety of genes overlapping with cancer relevant pathways. Our results further demonstrate the reliability of miRNA-based biomarkers for lung cancer prognostication and make a step forward to the application of miRNA biomarkers in the clinical routine.

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Section: Discussionmentioning

confidence: 99%

Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas

Dama

Melocchi

Mazzarelli

et al. 2020

ncRNA

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“…The National Comprehensive Cancer Network Guidelines recommends testing a panel of genes for NSCLC, which consists of epidermal growth factor ( EGFR ) mutations, anapestic lymphoma kinase ( ALK ) rearrangements, and c-ros oncogene 1 ( ROS1 ) rearrangements. These biomarkers are considered the “must-tests” biomarkers in lung cancer patient diagnosis and are analyzed by single-gene assays such as PCR, immunohistochemistry (IHC), and FISH [ 20 , 55 , 56 , 57 , 58 , 59 , 60 ]. Sanger sequencing, qPCR, ddPCR, IHC, and FISH are regarded as the gold standard techniques of molecular analysis in clinical practice, while tumor-only sequencing, matched-tumor, and normal-tissue sequencing are the gold standards in somatic mutation detection [ 18 , 61 ].…”

Section: Advancement Of Molecular Strategies and Techniques Used Tmentioning

confidence: 99%

“…An example is a new nomenclature for the adenocarcinoma subtype proposed by The Cancer Genome Atlas Consortium (TCGA). The TCGA′s classification integrated the transcriptional subtypes with the histopathological, anatomic, and mutational categorizations and consists of three subtypes that are characterized by specific genetic alterations ( Table 4 ) [ 56 ].…”

Section: Lung Cancer Genetic Heterogeneitymentioning

confidence: 99%

“…There are a number of other important recognized oncogenic alterations in lung adenocarcinoma that may be also used as potentially targetable alterations, including B-Raf proto-oncogene (BRAF), Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2), mesenchymal-epithelial transition factor (MET), and rearranged during transfection (RET). Current technologies such as the NGS approach reveal multiple gene alterations in a single tumor, however the co-occurrence of more than one oncogenic driver is infrequent [20,26,[56][57][58][59][60]. The data collected in the study of the Lung Cancer Mutation Consortium (Sholl et al, 2015) [70] revealed that, among 1007 lung adenocarcinomas, the co-occurrence of more than one oncogenic driver was found in only 3% of patients.…”

Section: Oncogenes and Tumor Suppressor Genes In Lung Cancermentioning

confidence: 99%

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Genetic Markers in Lung Cancer Diagnosis: A Review

Wadowska

Bil‐Lula

Trembecki

et al. 2020

IJMS

154

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Lung cancer is the most often diagnosed cancer in the world and the most frequent cause of cancer death. The prognosis for lung cancer is relatively poor and 75% of patients are diagnosed at its advanced stage. The currently used diagnostic tools are not sensitive enough and do not enable diagnosis at the early stage of the disease. Therefore, searching for new methods of early and accurate diagnosis of lung cancer is crucial for its effective treatment. Lung cancer is the result of multistage carcinogenesis with gradually increasing genetic and epigenetic changes. Screening for the characteristic genetic markers could enable the diagnosis of lung cancer at its early stage. The aim of this review was the summarization of both the preclinical and clinical approaches in the genetic diagnostics of lung cancer. The advancement of molecular strategies and analytic platforms makes it possible to analyze the genome changes leading to cancer development—i.e., the potential biomarkers of lung cancer. In the reviewed studies, the diagnostic values of microsatellite changes, DNA hypermethylation, and p53 and KRAS gene mutations, as well as microRNAs expression, have been analyzed as potential genetic markers. It seems that microRNAs and their expression profiles have the greatest diagnostic potential value in lung cancer diagnosis, but their quantification requires standardization.

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“…More recently, serum metabolites and lipids have emerged as another class of potential biomarkers in lung cancer [ 16 , 17 ]. Several other review papers could be suggested that cover this well-researched field [ 11 , 12 , 13 , 18 , 19 , 20 , 21 ]. However, though numerous biomarker candidates have been proposed only a few of them have been positively validated in the proper clinical settings.…”

Section: Introductionmentioning

confidence: 99%

Serum Exosomes and Their miRNA Load—A Potential Biomarker of Lung Cancer

Smolarz

Widłak

2021

Cancers

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Early detection of lung cancer in screening programs is a rational way to reduce mortality associated with this malignancy. Low-dose computed tomography, a diagnostic tool used in lung cancer screening, generates a relatively large number of false-positive results, and its complementation with molecular biomarkers would greatly improve the effectiveness of such programs. Several biomarkers of lung cancer based on different components of blood, including miRNA signatures, were proposed. However, only a few of them have been positively validated in the context of early cancer detection yet, which imposes a constant need for new biomarker candidates. An emerging source of cancer biomarkers are exosomes and other types of extracellular vesicles circulating in body fluids. Hence, different molecular components of serum/plasma-derived exosomes were tested and showed different levels in lung cancer patients and healthy individuals. Several studies focused on the miRNA component of these vesicles. Proposed signatures of exosome miRNA had promising diagnostic value, though none of them have yet been clinically validated. These signatures involved a few dozen miRNA species overall, including a few species that recurred in different signatures. It is worth noting that all these miRNA species have cancer-related functions and have been associated with lung cancer progression. Moreover, a few of them, including known oncomirs miR-17, miR-19, miR-21, and miR-221, appeared in multiple miRNA signatures of lung cancer based on both the whole serum/plasma and serum/plasma-derived exosomes.

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Deciphering the Molecular Profile of Lung Cancer: New Strategies for the Early Detection and Prognostic Stratification

Cited by 8 publications

References 98 publications

Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas

Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas

Genetic Markers in Lung Cancer Diagnosis: A Review

Serum Exosomes and Their miRNA Load—A Potential Biomarker of Lung Cancer

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