Small-scale external quality assessment of methylated SHOX2 and RASSF1A detection in China: findings from 2023–2024
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Chengxiang Chu
,
Chunli Shi
and
Xueliang Wang
Abstract
Objectives
DNA methylation in short homeobox gene 2 (SHOX2) and RAS association domain family protein 1 (RASSF1A) shows significant auxiliary diagnostic value for early-stage lung cancer. However, the detection accuracy is frequently compromised because of the complexity of the analytical procedures. This pilot external quality assessment (EQA) study evaluated the performance of methylated SHOX2 (mSHOX2) and methylated RASSF1A (mRASSF1A) detection across clinical laboratories in China.
Methods
A sample panel was prepared containing two mSHOX2-positive samples, one mRASSF1A-positive sample, one mSHOX2 and mRASSF1A double-positive sample, and one negative sample. The panel was randomly coded and distributed to clinical laboratories for mSHOX2 and mRASSF1A detection in 2023 and 2024. The returned results were compared and scored to evaluate laboratory performance.
Results
The sample panel demonstrated sufficient stability and applicability. Results were collected from 21 laboratories in 2023 and 29 laboratories in 2024. Approximately 90.5 % (19/21) and 75.9 % (22/29) laboratories achieved correct results in 2023 and 2024, respectively. Out of the 105 results in 2023 and 145 results in 2024, 1 false negative and 3 false positives were observed in 2023 and 6 false negatives and 12 false positives in 2024.
Conclusions
This two-round EQA study in China emphasizes the need for improvement in the performance of mSHOX2 and mRASSF1A methylation detection. These results underscore the critical role of EQA schemes in monitoring and improving the detection quality in clinical laboratories. To address the challenges in mSHOX2 and mRASSF1A detection, targeted recommendations are proposed to enhance detection accuracy and reliability.
Funding source: Shanghai Municipal Health Commission
Award Identifier / Grant number: No. 202240270
Funding source: Shanghai Public Health Research Program
Award Identifier / Grant number: No. 2024GKQ13
Funding source: Shanghai Center for Clinical Laboratory
Award Identifier / Grant number: No. 2024RCJH-04
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Research ethics: Ethical approval for the use of the urine samples was obtained from the Ethical Committee of the Shanghai Center for Clinical Laboratory (No. 202401).
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Informed consent: Not applicable.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: This work was supported by the Shanghai Public Health Research Program (No. 2024GKQ13), the Shanghai Center for Clinical Laboratory (No. 2024RCJH-04), and the Shanghai Municipal Health Commission (No. 202240270).
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Data availability: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0846).
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