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Table 2 Methylation-, gene-expression- and miRNA-based biomarkers for risks and early detection of lung cancer

From: Bridging the clinical gaps: genetic, epigenetic and transcriptomic biomarkers for the early detection of lung cancer in the post-National Lung Screening Trial era

Reference

Sample type

Genetics/genomics platform

Clinical settings

Key findings

a) Epigenetic biomarkers

[59]

Sputum, lung tissue, biopsies

MSP

Lung tissue, precursor lesions and bronchial biopsies from patients with SCC and sputum from individuals with suspicion of lung cancer

CDKN21 hypermethylation more often observed in patients with cancer than with no cancer

[66]

Paired serum and lung tissue

MSP

Lung tissue and serum from patients with NSCLC and control

73% of patients had serum DNA that reflected aberrant methylation in their tumors, specifically in CDKN2A, MGMT, DAPK, GSTP1

[60]

Paired sputum and lung tissue

MSP

Lung tissue and sputum from smokers with SCC

CDKN2A and MGMT were hypermethylated in both sputum and tumor of patients at time of diagnosis

[72]

Bronchial epithelial cells, blood lymphocytes, lung tissue

MSP

Paired blood and bronchial epithelial samples from smokers/non-smokers with pre-neoplastic lesions and neoplastic lesions from individuals with NSCL versus controls

ECAD and DAPK more likely to be methylated in smokers’ peripheral lymphocytes or bronchial epithelium and never methylated in non-smokers

[58]

Peripheral blood leukocytes

Illumina Beadchip and Pyrosequencing

Smokers with recently diagnosed SCLC and controls

Forty-three CpG sites were differentially methylated between SCLC and controls, and nine of these, validated by pyrosequencing, could discriminate SCLC with AUC of 0.86

[71]

Paired serum and lung tissue

MSP

Paired serum and lung tissue samples from individuals with lung cancer and controls

Six-gene serum panel that discriminated patients with lung cancer with 75% sensitivity and 73% specificity

b) Transcriptomics biomarkers

[76]

Bronchial brushing, large airway epithelium

Affymetrix array

Bronchial brushings of cytologically normal large airway eptihelium obtained from smokers undergoing bronchoscopy for suspicion of lung cancer

Eighty gene airway biomarker with >80% diagnostic sensitivity and specificity, and 95% sensitivity and negative predictive value when biomarker is combined with cytology collected at bronchoscopy

[78]

Bronchial brushings from normal airway bronchial epithelial cells

(StaRT)-PCR

Normal bronchial epithelial cells of patients with lung cancer and non-lung cancer controls

Fourteen gene airway biomarkers of antioxidant, DNA repair and transcription factor genes with performance in a test AUC >0.84 and an accuracy of 80%

[86]

Peripheral blood mononuclear cells

cDNA array

Blood collection from smokers with newly diagnosed lung cancer confirmed by histopathology

twenty-nine-gene blood signature with >80% sensitivity and specificity

[79]

Bronchial brushing from airway epithelium

Affymetrix array

Bronchial airway brushings of cytologically normal epithelium from smokers with and without lung cancer or premalignancy

Gene-expression signature of PI3K signaling pathway activation was differentially expressed in airways of smokers with lung cancer or dysplasia and was reversible with chemopreventive therapy

[88]

Whole blood

Sentrix whole genome bead chips WG6 (Illumina)

PAX gene-stabilized blood samples from three independent groups consisting of patients with NSCLC and controls

Genes differently expressed in whole blood of patients with NSCLC and controls were used to build a diagnostic classifier with AUC >0.82

[85]

Saliva

Affymetrix array

Whole saliva collected from untreated patients with lung cancer with matched cancer-free controls

Seven highly discriminatory transcriptomic salivary biomarker with AUC = 0.925 with >82% sensitivity and specificity

c) MicroRNA biomarkers

[93]

Sputum

RT-qPCR

Sputum from patients with squamous lung cancer and healthy controls

Three miRNA diagnosed stage I squamous cell lung cancer with AUC = 0.87

[94]

Sputum

RT-qPCR

Sputum from patients with lung adenocarcinoma and healthy controls

Four miRNA diagnosed stage I lung adenocarcinoma with AUC = 0.90

[107]

Serum

Genoexplorer microRNA expression system

Serum from patients with lung cancer versus healthy controls

Two miRNA discriminated individuals with early stages NSCLC with AUC = 0.77

[103]

Serum

Taqman Low Density Arrays RT-qPCR

Serum from asymptomatic patients with NSCLC and healthy smokers. Patients were screened by low-dose CT and sera were collected at the time of diagnosis before the surgery

Thirty-two miRNA predicted risk of developing lung cancer in asymptomatic high-risk individuals with an accuracy of 80%

[109]

Plasma

Taqman Low Density Arrays RT-qPCR

Multiple plasma samples were collected before and at the time of disease, from two independent spiral CT-screening trials

Fifteen miRNA predicted the risk of lung cancer with AUC = 0.85 and 13 miRNA diagnosed lung cancer in undetermined CT nodules with AUC = 0.88

[110]

Plasma

RT-qPCR

Plasma from patients with lung cancer versus healthy controls

Four miRNAs discriminated patients with NSCLC with AUC = 0.93

[105]

Serum

RT-qPCR

Serum from patients with lung cancer versus healthy controls

Ten miRNAs discriminated patients with NSCLC with AUC = 0.97