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. 2023 Apr 24;13:6620. doi: 10.1038/s41598-023-33698-8

Table 4.

Exhaled microRNA RF models.

RF models, lower stringency Individual component factors Accuracy (p-value) Sensi, Speci PPV, NPV ROC-AUC AUC difference, Clinical versus Clinical + micro-RNA, % (p-value)
All subjects, all smoking categories, all tumor histologies, n = 166 cases, 185 controls
 Clinical variables alone (unselected) All clinical variables [age, gender, smoking status, pack-years, quit-years, underlying lung disease, tumor histology for cases]

0.74

(< 2.2e−16)

0.74,

0.74

0.76,

0.72

0.814
 microRNAs alone

All 24 microRNAs

Important miRs: 21, 33b, 944, 1269a, 1910

0.57

(< 2.2e−16)

0.63,

0.50

0.58,

0.55

0.611
 Clinical + microRNA All Clinical factors and All 24 miRs

0.74

(2e−16)

0.74,

0.74

0.76,

0.73

0.826 1.2% (0.07)
Former smokers only n = 79cases, 77 controls
 Clinical variables alone All clinical variables [age, gender, smoking status, pack-years, quit-years, underlying lung disease]

0.69

(< 2.2e−16)

0.69

0.69

0.69

0.70

0.777
 microRNAs alone

All 24 microRNAs

Important miRs: 33b, 146a.5p, 200a, 212, 1293

0.59

(< 2.0e−16)

0.57

0.61

0.59

0.59

0.656
 Clinical + microRNA All Clinical and All miRs

0.70

(< 2.0e−16)

0.67

0.72

0.70

0.69

0.807 3.0% (6.0e−03)
Early stage only (stages I and II) n = 78 cases, 184 controls
 Clinical Variables Alone All clinical variables [age, gender, smoking status, pack-years, quit-years, underlying lung disease]

0.75

(2.2e−16)

0.86

0.50

0.80,

0.60

0.806
 microRNAs alone

All 24 microRNAs

Important miRs: 96, 146a.5p, 944, 1269a, 1910

0.700

(NS)

0.90,

0.23

0.73

0.49

 Clinical + microRNA All Clinical variables and All miRs

0.76

(< 2.2e−16)

0.90,

0.45

0.79

0.65

0.828 (2.2% (5.1e−03)
Former Smoker x Early Stage Sub-subgroup n = 34 cases, 77 controls
 Clinical variables alone All clinical variables [age, gender, smoking status, pack-years, quit-years, underlying lung disease, tumor histology for cases]

0.71

(1.9e−03)

0.87

0.35

0.75

0.54

0.714
 microRNAs alone

All 24 microRNAs

Important miRs: 96, 146a.5p, 200b, 345, 1910

0.67

(NS)

0.86

0.25

0.72

0.44

0.641
 Clinical + microRNA All Clinical and All miRs

0.71

(1.4e−02)

0.90

0.28

0.74

0.54

0.738 2.4% (NS)
Current Smokers only, n = 38cases, 72 controls
 Clinical variables alone All clinical variables [age, gender, smoking status, pack-years, quit-years, underlying lung disease, tumor histology for cases]

0.78

(2.2e−16)

0.59

0.87

0.71

0.80

0.731
 microRNAs alone

All 24 microRNAs

Important miRs: 105, 146a.5p, 182.5p, 200a, 205

0.59

(NS)

0.15

0.82

0.30

0.65

0.464
 Clinical + microRNA All Clinical and All miRs 0.76 (2.2e−16)

0.48

0.90

0.73

0.77

0.764 3.3% (3.5e−02)
Adenocarcinoma only, n = 87cases, 184 controls
 Clinical variables alone All clinical variables [age, gender, smoking status, pack-years, quit-years, underlying lung disease]

0.74

(< 2.2e−16)

0.83

0.53

0.79

0.60

0.817
 microRNAs alone

All 24 microRNAs

Important miRs: 96, 146a.5p, 221, 944, 1269a

0.65

(NS)

0.87

0.18

0.69

0.40

0.579
 Clinical + microRNA All Clinical and All miRs

0.73

(2.2e−16)

0.87

0.43

0.76

0.61

0.796 −2.1% (1.1e−02), neg direction
Late Stage (III, IV) only, n = 77cases, 184 controls
 Clinical variables alone All clinical variables [age, gender, smoking status, pack-years, quit years, underlying lung disease, underlying lung disease] 0.74 (2.2e−16)

0.84

0.49

0.80

0.56

0.797
 microRNAs alone

All 24 microRNAs

Important miRs: 31, 33b, 105, 212, 944

0.67

(NS)

0.90

0.12

0.71

0.35

0.541
 Clinical + microRNA All Clinical and All miRs 0.74 (2.2e−16)

089

0.38

0.77

0.58

0.809 1.2% (NS)
Late Stage (III, IV) x Former Smoker, n = 40 cases, 77 controls
 Clinical variables alone All clinical variables [age, gender, smoking status, pack-years, quit years, underlying lung disease, underlying lung disease] histologies?]

0.70

(1.6e−13)

0.82

0.46

0.75

0.57

0.781
 microRNAs alone

All 24 microRNAs

Important miRs: 33b, 200a, 212, 345, 1293

0.63

(NS)

0.84

0.22

0.67

0.41

0.654
 Clinical + microRNA All Clinical and All miRs 0.69 (1.1e−07)

0.85

0.37

0.72

0.57

0.789 0.8% (NS)

RF Models of case–control distinction, including clinical variables alone, exhaled microRNAs alone, and the two combined, and performance characteristics of accuracy, sensitivity, specificity, positive and negative predictive value (PPV, NPV, resp.), Underlying lung disease is treated as a (trichotomous) variable: (3). COPD or fibrosis or inflammation or asthma (all carry some lung cancer risk); versus (2). sarcoid bronchiectasis; versus (1) none/other).