四川大学学报（医学版）2026，Vol.57Issue(2)：411-418,8.DOI:10.12182/20260360603
宏基因组二代测序在毛霉菌病诊断中的效能评估:一项回顾性队列研究
Diagnostic Performance of Metagenomic Next-Generation Sequencing for Mucormycosis:A Retrospective Cohort Study
摘要
Abstract
Objective Mucormycosis is a life-threatening invasive fungal infection with high mortality,yet traditional diagnostic methods are limited by low positivity rates.This study aims to evaluate the diagnostic performance and clinical utility of metagenomic next-generation sequencing(mNGS)in mucormycosis.Methods A retrospective analysis was conducted on 135 patients with mNGS results positive for Mucorales fungi at West China Hospital of Sichuan University from November 1,2022,to October 31,2024.Based on comprehensive clinical diagnostic criteria(including proven and probable cases),patients were classified into a confirmed mucormycosis group and a non-mucormycosis group.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic performance of normalized read counts(lgRPM)from different specimen types.Fungal species distribution and laboratory parameters were compared between the two groups.Results Among the 135 patients with positive mNGS results for Mucorales,100(74.1%)were ultimately diagnosed with mucormycosis.ROC curve analysis revealed that the diagnostic performance of mNGS varied by specimen type.For blood specimens,the area under the curve(AUC)was 0.772,with a specificity of 87.5%at the optimal cutoff value of 0.11 RPM.For bronchoalveolar lavage fluid specimens,the AUC was 0.717,with a sensitivity of 76.5%at the optimal cutoff value of 0.02 RPM.Combined analysis of all specimens showed that at the optimal cutoff value of 0.08 RPM(approximately 8 reads/100M),the sensitivity and specificity were 62.0%and 71.4%,respectively.Species distribution analysis showed that the proportions of Cunninghamella elegans(11.0%vs.2.9%)and Rhizomucor pusillus(9.0%vs.2.9%)were significantly higher in the confirmed group than in the non-mucormycosis group(P<0.05).Levels of C-reactive protein and interleukin-6 were also significantly higher in the confirmed group(P<0.05).Notably,all seven renal perfusion fluid samples yielded false-positive mNGS results.Conclusion mNGS technology can effectively improve the diagnostic yield for mucormycosis.However,results should be interpreted in conjunction with specimen type,read count,and clinical characteristics.BALF specimens offer high sensitivity,making them suitable for screening,while blood specimens demonstrate high specificity,making them valuable for confirmation.Positive results from low-biomass samples such as renal perfusion fluid warrant caution against false positivity.Fungal species identification and inflammatory markers may serve as adjunctive evidence for clinical diagnosis.关键词
毛霉菌病/宏基因组二代测序/诊断效能/菌种分布Key words
Mucormycosis/Metagenomic next-generation sequencing/Diagnostic performance/Species distribution引用本文复制引用
张为利,钟山,陆思芬,肖侠,谢轶..宏基因组二代测序在毛霉菌病诊断中的效能评估:一项回顾性队列研究[J].四川大学学报（医学版）,2026,57(2):411-418,8.基金项目
This study was supported by the National Science and Technology Major Project for Research on Prevention and Treatment of Cancer,Cardiovascular and Cerebrovascular Diseases,and Respiratory and Metabolic Diseases(No.2024ZD0532800). 癌症、心脑血管、呼吸和代谢性疾病防治研究国家科技重大专项(No.2024ZD0532800)资助 （No.2024ZD0532800）
