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 |