Development of the semi-dry dot-blot method for intraoperative detecting micropapillary component in lung adenocarcinoma based on proteomics analysis

基于蛋白质组学分析的肺腺癌术中微乳头成分半干斑点印迹检测方法的开发

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作者:Long Xu #, Hang Su #, Shengnan Zhao #, Haojie Si, Huikang Xie, Yijiu Ren, Jiani Gao, Fang Wang, Xiaofeng Xie, Chenyang Dai, Chunyan Wu, Deping Zhao, Chang Chen; Surgical Thoracic Alliance of Rising Star Group

Background

Micropapillary (MIP) component was a major concern in determining surgical strategy in lung adenocarcinoma (LUAD). We sought to develop a novel method for detecting MIP component during surgery.

Conclusions

Intraoperative examination of CRABP2 using SDB method to detect MIP component reached comparable performance to pathologist, and SDB method had notable superiority than pathologist in detecting minor MIP component.

Methods

Differentially expressed proteins between MIP-positive and MIP-negative LUAD were identified through proteomics analysis. The semi-dry dot-blot (SDB) method which visualises the targeted protein was developed to detect MIP component.

Results

Cellular retinoic acid-binding protein 2 (CRABP2) was significantly upregulated in MIP-positive LUAD (P < 0.001), and the high CRABP2 expression zone showed spatial consistency with MIP component. CRABP2 expression was also associated with decreased recurrence-free survival (P < 0.001). In the prospective cohort, the accuracy and sensitivity of detecting MIP component using SDB method by visualising CRABP2 were 82.2% and 72.7%, which were comparable to these of pathologist. Pathologist with the aid of SDB method would improve greatly in diagnostic accuracy (86.4%) and sensitivity (78.2%). In patients with minor MIP component (≤5%), the sensitivity of SDB method (63.6%) was significantly higher than pathologist (45.4%). Conclusions: Intraoperative examination of CRABP2 using SDB method to detect MIP component reached comparable performance to pathologist, and SDB method had notable superiority than pathologist in detecting minor MIP component.

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