Dataset Information

Bronchial Washing Fluid Versus Plasma and Bronchoscopy Biopsy Samples for Detecting Epidermal Growth Factor Receptor Mutation Status in Lung Cancer.

ABSTRACT:

Background

Bronchial washing fluid (BWF) is a common specimen collected during bronchoscopy and has been suggested to contain both tumor cells and cell-free DNA. However, there is no consensus on the feasibility of BWF in epidermal growth factor receptor (EGFR) genetic analysis because of the limited sample size and varying results in previous studies. This study compared the feasibility, sensitivity, and specificity of detecting EGFR mutation using BWF, bronchoscopy biopsy, and plasma samples in patients with lung cancer (LC).

Materials and methods

A total of 144 patients (110 with LC and 34 without LC) were enrolled in the study. During diagnostic bronchoscopy for suspected LC lesions, bronchial washing with saline was performed directly or through a guide sheath. BWF was collected as well as paired bronchoscopy biopsy and plasma samples, and EGFR mutation testing was performed via highly sensitive blocker polymerase chain reaction. The EGFR mutation status of histologic samples was set as the standard reference.

Results

Compared with the histologic samples, the sensitivity, specificity, and concordance rate of EGFR mutation detected in BWF samples were 92.5%, 100%, and 97.9%, respectively. Moreover, BWF showed a higher sensitivity in EGFR mutation testing than both plasma (100% [8/8] vs. 62.5% [5/8], p = 0.095) and bronchoscopy biopsy samples (92.5% [37/40] vs. 77.5% [31/40], p = 0.012) and identified EGFR mutations in 6 cases whose biopsy failed to establish an LC diagnosis. The diameter of the target lesion and its contact degree with BWF were positive predictive factors for EGFR testing results.

Conclusions

BWF yields a high sensitivity in EGFR mutation testing, having high concordance with histologic samples, and presenting the benefit of rapid EGFR mutation detection in LC patients.

SUBMITTER: Zhang X

PROVIDER: S-EPMC8020887 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Objective: With the rapid development of cancer genomics and immunomics, some new treatments of small cell lung cancer (SCLC) are emerging. However, there are limitations to the clinical use of tumor tissue. Our study aimed to evaluate the potential use of bronchial washing fluid (BWF) in the liquid biopsy of SCLC. Methods: Twenty-one extensive SCLC (ES-SCLC) patients were enrolled in this study. For all patients, four sample types, BWF supernatant (BWFs), BWF precipitate (BWFp), plasma and tumor tissue, were collected before receiving chemotherapy, and one type, plasma, was collected after chemotherapy. All samples were conducted to NGS using the 1021-gene panel. The concordance rates of genomic profiling using NGS in the four types of samples were evaluated. Multiple clinical information was analyzed for correlation. Results: We successfully tested 20 BWFs samples, 21 BWFp samples, 21 tumor tissue samples, 20 pre-treatment plasma, and 13 post-treatment plasma of these 21 patients. The detectability of somatic mutations was 100% for BWFs, BWFp, tumor tissues, and post-treatment plasma, and only one pre-treatment plasma was absent with any mutation. Matched tumor tissue, BWFs, BWFp, and pre-treatment plasma samples were subsistent for 19 patients. For these patients, 204 genomic alterations were identified in tissue samples, while 189 (92.6%), 175 (85.5%), and 163 (79.9%) alterations were detected in the matched BWFs, BWFp, and pre-treatment plasma, respectively. Moreover, we found that the three tumor markers associated with SCLC have a lower sensitivity than genomic alterations. The endocrine resistance pathway was found enriched in hyponatremia patients which may be related to the hyponatremia. The TMBs of BWF, BWFp, and pre-treatment plasma samples all had a strong correlation with that of tissue samples. Both the VAF and the MVAF of mutations in post-treatment plasma were less than those in pre-treatment plasma, which was in accordance with the evaluation of curative effect. Conclusions: For ES-SCLC patients, the liquid biopsy of BWF showed a highly potential advantage to identify DNA alterations, which suggested that genomic analysis of BWF liquid biopsy may have clinical value as a supplement for tissue and blood detection. Through the restricted validation, it can be widely used in routine clinical practice.

Project description:Bronchoscopy is a frequently used initial diagnostic procedure for patients with suspected lung cancer (LC). Cytological examinations of bronchial washing (BW) samples obtained during bronchoscopy often yield inconclusive results regarding LC diagnosis. The present study aimed to identify molecular biomarkers as a non-invasive method for LC diagnosis. Aberrant DNA methylation is used as a useful biomarker for LC. Therefore, microarray-based methylation profiling analyses on 13 patient-matched tumor tissues at stages I-III vs. non-tumor tissues were performed, and a group of highly differentially methylated genes was identified. A subsequent analysis using bisulfite-pyrosequencing with additional tissues and cell lines revealed six methylated genes [ADAM metallopeptidase with thrombospondin type 1 motif 20, forkhead box C2 (mesenchyme forkhead 1), NK2 transcription factor related, locus 5 (Drosophila), oligodendrocyte transcription factor 3, protocadherin γ subfamily A 12 (PCDHGA12) and paired related homeobox 1 (PRRX1)] associated with LC. Next, a highly sensitive and accurate detection method, linear target enrichment-quantitative methylation-specific PCR in a single closed tube, was applied for clinical validation using BW samples from patients with LC (n=68) and individuals with benign diseases (n=33). PCDHGA12 and PRRX1 methylation were identified as the best-performing biomarkers to detect LC. The two-marker combination showed a sensitivity of 82.4% and a specificity of 87.9%, with an area under the curve of 0.891. Notably, the sensitivity for small cell LC was 100%. The two-marker combination had a positive predictive value of 93.3% and a negative predictive value of 70.7%. The sensitivity was higher than that of cytology, which only had a sensitivity of 50%. The methylation status of the two-marker combination showed no association with sex, age or stage, but was associated with tumor location and histology. In conclusion, the present study showed that the regulatory regions of PCDHGA12 and PRRX1 are highly methylated in LC and can be used to detect LC in BW specimens as a diagnostic adjunct to cytology in clinical practice.