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Molecular Diagnostics

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

British Journal of Cancer volume 128, pages 2116–2125 (2023)Cite this article

Subjects

Abstract

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.

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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Fig. 1: The flow diagram of SDB method for detecting micropapillary.
Fig. 2: Identification and validation of targeted proteins for SDB method.
Fig. 3: Validation of SDB method for detecting MIP component through colorimetric comparison.
Fig. 4: Performance of SDB method for detecting MIP component and compare it with pathologist.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

This work was supported by the National Key Research and Development Program of China (grant no. 2022YFC2407401), the Shanghai Hospital Development Center (SHDC2020CR1021B and SHDC22021217), Shanghai Municipal Health Commission (202040322 and 20194Y0129), Shanghai Science and Technology Commission (20XD1403000 and 21S31905200).

Author information

Author notes

  1. These authors contributed equally: Long Xu, Hang Su, Shengnan Zhao.

Authors and Affiliations

  1. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China

    Long Xu, Hang Su, Haojie Si, Yijiu Ren, Jiani Gao, Fang Wang, Chenyang Dai & Deping Zhao

  2. Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China

    Shengnan Zhao, Huikang Xie, Xiaofeng Xie & Chunyan Wu

  3. Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Clinical Center for Thoracic Surgery Research, Tongji University, Shanghai, People’s Republic of China

    Chang Chen

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Consortia

Surgical Thoracic Alliance of Rising Star Group

  • 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

Contributions

Conception and design: LX, HS, SZ, DZ and CC; Administrative support: CW, DZ and CC; Provision of study materials or patients: CW, DZ and CC; Collection and assembly of data: HS, HX, YR, JG, FW, XX and CD. Data analysis and interpretation: LX, HS and SZ. Manuscript writing: All authors; Final approval of manuscript: All authors.

Corresponding authors

Correspondence to Deping Zhao or Chang Chen.

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The authors declare no competing interests.

Ethics approval and consent to participate

The institutional review board of Shanghai Pulmonary Hospital affiliated to Tongji University approved this study (IRB NO: L21-340).

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Xu, L., Su, H., Zhao, S. et al. Development of the semi-dry dot-blot method for intraoperative detecting micropapillary component in lung adenocarcinoma based on proteomics analysis. Br J Cancer 128, 2116–2125 (2023). https://doi.org/10.1038/s41416-023-02241-x

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