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

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.

Keywords: Biomarker; Graphene chip; Metastasis; Ovarian cancer; Rapid detection; SAA1.