Zhao Yilin, Chen Yao, Wan Qi, Xiao Chengju, Guo Zhiqing, Du Xinjie, Hu Yan, Zheng Ai, Cao Zhongwei
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.
Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.
J Cancer Res Clin Oncol. 2023 Dec;149(18):16391-16406. doi: 10.1007/s00432-023-05296-8. Epub 2023 Sep 14.
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.
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.
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.
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.
卵巢癌（OC）是一种常见的妇科恶性肿瘤，死亡率最高，由于缺乏有效的早期筛查方法和非特异性症状，通常在晚期才被诊断出来。因此，我们旨在识别新的转移标志物，并开发一种与其他传统检测技术相比具有高灵敏度、快速检测、高特异性和低成本特点的新型检测方法。
收集有或无转移的OC患者血液，采用4D无标记液相色谱-串联质谱（LC - MS/MS）进行分析。收集OC患者手术切除样本进行单细胞RNA测序（sc-RNA seq）。使用短发夹RNA（shRNA）沉默SKOV3和ID8中SAA1的表达，以验证内源性SAA1与肿瘤侵袭或转移之间的关系。通过共价结合制备的功能性石墨烯芯片用于SAA1检测。
在我们的研究中，通过对有或无转移的OC患者血浆中的蛋白质进行综合分析，使用4D无标记LC - MS/MS以及来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的基因表达模式，我们确定血清淀粉样蛋白A1（SAA1）为OC转移的血液学标志物。使用人OC和小鼠OC模型的肿瘤组织和血浆进行的进一步验证证实了SAA1与肿瘤转移之间的相关性。重要的是，人OC样本的sc-RNA seq显示SAA1在肿瘤细胞中特异性表达，并在转移组中上调。通过体内外实验证明了SAA1在转移中的功能作用。基于这些发现，我们设计并研究了一种基于石墨烯的平台用于SAA1检测，以预测OC患者的转移风险。
我们的研究表明SAA1是OC转移的生物标志物，并且我们已经开发了一种快速且高度灵敏的平台，使用石墨烯芯片检测血浆SAA1，用于早期评估OC患者的转移情况。
