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Identification of SAA1 as a novel metastasis marker in ovarian cancer and development of a graphene-based detection platform for early assessment

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Abstract

Background

Ovarian cancer (OC) is a prevalent gynecological malignancy with the highest mortality rate, which generally diagnosed at late stages due to the lack of effective early screening methods and the nonspecific symptoms. Hence, here we aim to identify new metastasis markers and develop a novel detection method with the characteristics of high sensitivity, rapid detection, high specificity, and low cost when compared with other conventional detection technologies.

Methods

Blood from OC patients with or without metastasis were collected and analyzed by 4D Label free LC − MS/MS. Surgically resect samples from OC patients were collected for Single cell RNA sequencing (sc-RNA seq). Short hairpin RNA (shRNA) was used to silence SAA1 expression in SKOV3 and ID8 to verify the relationship between endogenous SAA1 and tumor invasion or metastasis. The functional graphene chips prepared by covalent binding were used for SAA1 detection.

Results

In our study, we identified Serum Amyloid A1 (SAA1) as a hematological marker of OC metastasis by comprehensive analysis of proteins in plasma from OC patients with or without metastasis using 4D Label free LC − MS/MS and gene expression patterns from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Further validation using tumor tissues and plasma from human OC and mouse OC model confirmed the correlation between SAA1 and tumor metastasis. Importantly, sc-RNA seq of human OC samples revealed that SAA1 was specifically expressed in tumor cells and upregulated in the metastasis group. The functional role of SAA1 in metastasis was demonstrated through experiments in vitro and in vivo. Based on these findings, we designed and investigated a graphene-based platform for SAA1 detection to predict the risk of metastasis of OC patients.

Conclusion

Our study suggests that SAA1 is a biomarker of OC metastasis, and we have developed a rapid and highly sensitive platform using graphene chips to detection of plasma SAA1 for the early assessment of metastasis in OC patients.

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Data availability statement

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

Abbreviations

OC:

Ovarian cancer

SAA:

Serum amyloid A

sc-RNA seq:

Single cell RNA sequencing

TCGA:

The cancer genome Atlas

GEO:

Gene expression omnibus

IHC:

Immunohistochemical

NAC:

Neoadjuvant chemotherapy

FIGO:

The International Federation of Gynecology and Obstetrics

HGSC:

High-grade serous carcinoma

CCC:

Clear-cell carcinoma

EC:

Endometrioid carcinoma

LBP:

Lipopolysaccharide-binding protein

HP:

Haptoglobin

PIGR:

Polymeric immunoglobulin receptor

shRNA:

Short hairpin RNA

PASE:

1-Pyrene-butanoic acid succinimidyl ester

FET:

Field effect transistor

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Acknowledgements

We are grateful to thank Bisen Ding (West China Second University Hospital, Sichuan University) for providing the ID8, SKOV3 and 293T cells. We would also like to thank Xiaoqing Tang and Xiangqi Chen (West China Second University Hospital, Sichuan University) for providing pLKO.1-TRC, pMD2.G and pSPAX2.

Funding

This work was supported by National Science Foundation of China (82125002, 00402154A1062), Sichuan Science and Technology Program (23NSFSC0014) and China Postdoctoral Science Foundation (0040214153014).

Author information

Author notes

  1. Yilin Zhao, Yao Chen and Qi Wan have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, No.17 Section 3, Renmin South Road, Chengdu, 610041, People’s Republic of China

    Yilin Zhao, Qi Wan, Chengju Xiao, Zhiqing Guo, Xinjie Du, Yan Hu, Ai Zheng & Zhongwei Cao

  2. Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China

    Yao Chen

  3. Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, 610041, China

    Qi Wan & Ai Zheng

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  1. Yilin Zhao
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Contributions

ZC, AZ and YH conceived and designed the study. YZ and ZG developed the study methodology. YZ, YC and XD acquired, analyzed, and/or interpreted data. QW constructed graphene chips and detected the plasma. CX analyzed the TCGA, GEO database and sc-RNA Seq data. ZC and YH wrote the original draft of the manuscript, and all authors wrote, reviewed, and/or revised the manuscript.

Corresponding authors

Correspondence to Yan Hu, Ai Zheng or Zhongwei Cao.

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Conflict of interest

The authors declare no competing interests.

Ethical approval

All recruited individuals gave written informed consent, and the ethics review board of the West China Second University Hospital, Sichuan University approved the protocol Medical Research 2020 (059).

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Zhao, Y., Chen, Y., Wan, Q. et al. Identification of SAA1 as a novel metastasis marker in ovarian cancer and development of a graphene-based detection platform for early assessment. J Cancer Res Clin Oncol 149, 16391–16406 (2023). https://doi.org/10.1007/s00432-023-05296-8

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