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Validating Methylated HOXA9 in Bronchial Lavage as a Diagnostic Tool in Patients Suspected of Lung Cancer.

ABSTRACT: Diagnosing lung cancer requires invasive procedures with high risk of complications. Methylated tumor DNA in bronchial lavage has previously shown potential as a diagnostic biomarker. We aimed to develop and validate methylated HOXA9 in bronchial lavage as a diagnostic biomarker of lung cancer. Participants were referred on suspicion of lung cancer. Ten mL lavage fluid was collected at bronchoscopy for analysis of methylated HOXA9 based on droplet digital PCR according to our previously published method. HOXA9 status was compared with the final diagnosis. The Discovery and Validation cohorts consisted of 101 and 95 consecutively enrolled participants, respectively. In the discovery cohort, the sensitivity and specificity were 73.1% (95% CI 60.9-83.2%) and 85.3% (95% CI 68.9-95.0%), respectively. In the validation cohort, the values were 80.0% (95% CI 66.3-90.0%) and 75.6% (95% CI 60.5-87.1%), respectively. A multiple logistic regression model including age, smoking status, and methylated HOXA9 status resulted in an AUC of 84.9% (95% CI 77.3-92.4%) and 85.9% (95% CI 78.4-93.4%) for the Discovery and Validation cohorts, respectively. Methylated HOXA9 in bronchial lavage holds potential as a supplementary tool in the diagnosis of lung cancer with a clinically relevant sensitivity and specificity. It remained significant when adjusting for age and smoking status.

SUBMITTER: Wen SWC

PROVIDER: S-EPMC8393370 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Validating Methylated HOXA9 in Bronchial Lavage as a Diagnostic Tool in Patients Suspected of Lung Cancer.

Wen Sara W C SWC Andersen Rikke F RF Rasmussen Kristian K Thomsen Caroline Brenner CB Hansen Torben Frøstrup TF Nederby Line L Hager Henrik H Jakobsen Anders A Hilberg Ole O

Cancers 20210822 16

Diagnosing lung cancer requires invasive procedures with high risk of complications. Methylated tumor DNA in bronchial lavage has previously shown potential as a diagnostic biomarker. We aimed to develop and validate methylated <i>HOXA9</i> in bronchial lavage as a diagnostic biomarker of lung cancer. Participants were referred on suspicion of lung cancer. Ten mL lavage fluid was collected at bronchoscopy for analysis of methylated <i>HOXA9</i> based on droplet digital PCR according to our previ ...[more]

PMID: 34439376

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Project description:BackgroundTo evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in immunocompromised patients for the diagnosis of suspected pneumonia in comparison with that of conventional microbiological tests (CMTs).MethodsSixty-nine immunocompromised patients with suspected pneumonia received both CMTs and mNGS of BALF were analyzed retrospectively. The diagnostic value was compared between CMTs and mNGS, using the clinical composite diagnosis as the reference standard.ResultsSixty patients were diagnosed of pneumonia including fifty-two patients with identified pathogens and eight patients with probable pathogens. Taking the composite reference standard as a gold standard, 42 pathogens were identified by CMTs including nine bacteria, 17 fungi, 8 virus, 6 Mycobacterium Tuberculosis, and two Legionella and 19(45%) of which were detected by BALF culture. As for mNGS, it identified 76 pathogens including 20 bacteria, 31 fungi, 14 virus, 5 Mycobacterium Tuberculosis, four Legionella and two Chlamydia psittaci. The overall detection rate of mNGS for pathogens were higher than that of CMTs. However, a comparable diagnostic accuracy of mNGS and CMTs were found for bacterial and viral infections. mNGS exhibited a higher diagnostic accuracy for fungal detection than CMTs (78% vs. 57%, P < 0.05), which mainly because of the high sensitivity of mNGS in patients with Pneumocystis jirovecii pneumonia (PJP) (100% vs. 28%, P < 0.05). Nineteen patients were identified as pulmonary co-infection, mNGS test showed a higher detection rate and broader spectrum for pathogen detection than that of CMTs in co-infection. Moreover, Pneumocystis jirovecii was the most common pathogen in co-infection and mNGS have identified much more co-pathogens of PJP than CMTs.ConclusionsmNGS of BALF improved the microbial detection rate of pathogens and exhibited remarkable advantages in detecting PJP and identifying co-infection in immunocompromised patients.

Dataset Information

Validating Methylated HOXA9 in Bronchial Lavage as a Diagnostic Tool in Patients Suspected of Lung Cancer.

Publications

Validating Methylated HOXA9 in Bronchial Lavage as a Diagnostic Tool in Patients Suspected of Lung Cancer.

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