Genetic analysis detection based on BALF for lung cancer
| Study population of BALF | Genetic mutations | Source of origin | Methods | Sn/Sp (%) | Comparison (Sn/Sp) (%) | Comments | Ref. |
|---|---|---|---|---|---|---|---|
| Lung adenocarcinoma (n = 33) | EGFR 33 | Cell pellet | Sanger sequencing | 9.09/NA | Pleural effusion: 13.3/NA (unpaired) | BALF cell NGS had higher sensitivity than Sanger sequencing, and therefore could be a diagnostic supplement for better characterization of lung cancer; BALF had higher sensitivity than pleural effusion. | 69 |
| NGS | 78.8/NA | Pleural effusion: 53.3/NA (unpaired) | |||||
| Lung adenocarcinoma (n = 20) | EGFR 12 vs. WT 8 | CfDNA | PNA-PCR and PANAMutyper† | 91.7/100 | Bronchial washing samples: 18.2/100 (paired) | BALF cfDNA was useful in detecting EGFR mutation and identifying T790M mutations; BALF was more useful than bronchial washing samples. | 70 |
| Lung adenocarcinoma (n = 26) | EGFR 13 vs. WT 13 | Mixture‡ | PCR | 92.3/100 | Peripheral blood: 38.5/100 (paired) | BALF had much higher diagnostic accuracy than blood for EGFR mutation detection; two additional mutations were identified in BALF compared with tissue biopsy. | 71 |
| Malignant (n = 31) and benign (n = 9) | Mutation profiling | CfDNA | NGS | 67.7/77.8 | Bronchoscopy biopsy: 23.1/100 (unpaired) Bronchial brushing cytology: 9.7/100 (unpaired) Lavage cytology: 3.1/100 (unpaired) Plasma methylation: 66.7/71.4 (unpaired) | BALF cfDNA methylation analysis had better sensitivity in distinguishing small malignant tumors (≤ 2 cm) from benign nodules than mutation analysis; both were better than conventional methods. | 72 |
| Malignant (n = 27) and benign (n = 21) | Methylation profiling | Bisulfite sequencing and RT-PCR | 81.5/81.0 | ||||
| Lung cancer stage I-II (n = 18) | Mutation profiling | CfDNA | Tumor naïve approach | 66.7/NA | Plasma cfDNA 11.1/NA (paired) | BALF cfDNA analysis was more sensitive than plasma cfDNA for detecting lung cancer-derived mutations in stage I-II disease. | 73 |
| Lung cancer stage I-II (n = 22) | Tumor-informed analysis | 77.3/NA | Plasma cfDNA: 45.5/NA (paired) | ||||
| Lung cancer (n = 17) and non-cancer (n = 16) | Genomic classifier | 64.7/100 | BAL cytology: 11.8/100 (paired) | BALF cfDNA analysis was useful for the diagnosis of lung cancer. | |||
| Lung cancer (n = 31) | Methylation of CDH1, APC, RASSF1A, MGMT, P16, GSTP1, ARF, and RAR-β2 | Cell pellet | RT-PCR and RT-MSP | 67.7/NA | NA | Aberrant DNA methylation was detected in the majority of lung cancer patients. | 74 |
| Lung cancer (n = 123); benign lung diseases (n = 112); malignancies in other systems (n = 18) | Methylation of SHOX2 and/or RASSF1A | Cell pellet | RT-PCR and Sanger sequencing | SHOX2: 64.2/92.3; RASSF1A: 50.4/96.2; SHOX2 and RASSF1A: 71.5/90.0 | BALF cytology: 5.7/99.2 | BALF cell methylation analysis (SHOX2 and RASSF1A) improved diagnostic accuracy for lung cancer, and was superior to cytology diagnosis. | 75 |
| Lung cancer (n = 284); benign lung diseases (n = 35); malignancies in other systems (n = 3) | Methylation of SHOX2 and RASSF1A | Cell pellet | RT-PCR and Sanger sequencing | Total: 81/97.4 Stage I: 85.7/NA | Total Cytology: 68.3/97.4; Serum CEA: 30.6/100 Stage I Cytology: 46.4/NA Serum CEA: 10.7/NA | BALF cell methylation analysis had relatively satisfactory diagnostic accuracy for lung cancer, especially at early stage, and was complementary to cytology diagnosis. | 76 |
Sn, sensitivity; Sp, specificity; NA, not available; NGS, next-generation sequencing; WT, wild type; PCR, polymerase chain reaction; PNA-PCR, peptide nucleic acid-mediated PCR; RT-PCR, real-time PCR; RT-MSP, real-time methylation-specific polymerase chain reaction.
↵†Indicates PANAMutyper™ R EGFR kit with PNA clamping-assisted fluorescence melting curve analysis was used for mutation detection and genotyping.
↵‡Indicates non-centrifuged BALF.