Table 1.
Summary of the noninvasive detection methods for lung cancer.
| Biomarkers/Specimen | Analytic Platform | Detection Target | Sensitivity (%) | Advantages | Deficiencies | Ref. |
|---|---|---|---|---|---|---|
| CTCs/Blood | IF; FISH | EpCAM, Size-based cells | 30.0–69.5 | Viable cell, high specificity, high throughput | Limited sensitivity; require enrichment; only detect advanced cancers | [14,15] |
| Traditional Proteins/Blood | ECLIA | CEA, CYFRA 21-1 | 22–69 | Rapid and common | Limited sensitivity and specificity | [16] |
| Novel Proteins/EBC, Saliva, Urine, Blood | Microarray; LC-MS/MS | CKAP4, exosomal proteins (NFX1, PKG1, GPC1) | 70.0–84.0 | Higher sensitivity; high throughput; rapid | Quantity required (MS); validation required | [17,18,19] |
| microRNA/Blood | Microarray; RT-PCR; NGS | miRNAs-126, -145, -210 and -205-5p, -17, -190b, -19a, -19b, -26b, -375 | 80.0–91.5 | High throughput, stable | Specialized abilities and facilities are required | [20,21,22,23,24] |
| Methylated DNA/Blood | NGS; PCR | HOXD10, PAX9, PTPRN2, STAG3, SHOX2 | 70.0–87.8 | High sensitivity and specificity | Require standardization | [25,26,27] |
| ctDNA/Blood | NGS; Multiplex-PCR | Genetic mutation, SNVs | 48.0–59.0 | Target for precision medicine; early detection (~70 days prior to CT image) | Limited sensitivity, require expensive equipment | [28,29,30] |
| VOCs/Exhaled Breath | E-Nose sensors; GC-MS; PTR-MS, IMS; LPPI-MS | propanol, isoprene, acetone, pentane, hexanal, toluene, benzene, ethylbenzene, and others | 81.0–96.5 | Rapid, simple, noninvasive; inexpensive | Require standardization | [7,31,32] |
Abbreviations: CTCs (circulating tumor cells); IF (immunofluorescence); FISH (fluorescence in situ hybridization); EpCAM (epithelial cell adhesion molecule); ECLIA (electrochemiluminescence immunoassay); CEA (carcinoembryonic antigen); CYFRA 21-1 (cytokeratin fraction 21-1); EBC (exhaled breath condensate); NGS (next-generation sequencing); CT(computed tomography); RT-PCR (reverse transcription PCR); ctDNA (circulating tumor DNA); SNVs (single-nucleotide variants); GC-MS (gas chromatography mass spectrometry); PTR-MS (proton transfer reaction mass spectrometry); IMS (ion mobility spectrometry); LPPI-MS (low-pressure photoionization mass spectrometry); VOCs (volatile organic compounds).