24P - High-throughput plasma proteomics profiling in early breast cancer

Background

Non-invasive early diagnosis of cancer is a highly desirable goal in oncology. Plasma proteins have potential application in clinical practice as cancer biomarker. However, their profiling in presence of small tumors, entails technical and biological challenges. Cutting-edge technologies could overcome these limitations. In the present study, we describe preliminary data on the assessment of circulating proteins in early breast cancer (eBC) patients from the RENOVATE trial by employing two high-throughput proteomics approaches.

Methods

The RENOVATE trial (NCT04781062) enrolled women with suspect breast lesions ≤ 2 cm. They were asked to donate blood sample (detailed information in Ravera et al., BMJ, 2021). Plasma samples from 31 cancer, 29 benign and 20 healthy donors, matched by age, body mass index (BMI), menopausal and smoking status, were tested by aptamer-based proteomics arrays (SomaScan Somalogic®). Nearly 370 proteins were reassessed on the same biospecimens, leveraging an antibody-DNA linker technology assay (Oncology panel, Olink®). Variance analysis was performed using ANOVA. Statistical tests with a p-value < 0.01 were considered significant. Proteomics signatures were identified by a penalized linear model (glmnet R package). The two assays correlation was evaluated using Intra-class correlation (ICC).

Results

Out of 7596 proteins, 29 showed a significant differences across the 3 groups. The detected proteins are mainly involved in differentiation, migration, and cell death pathways. The two platforms shared 300 targets; 99% (n=296) passed the quality control step. The two used methodologies displayed moderately consistent results with 22% of probes (n=66) with an ICC index ≥ 0.5.

Conclusions

In the present study, we performed a broad analysis of human circulating proteins. We detected proteins associated with early BC related to pathways influencing cancer development. Data were validated by an orthogonal technology. Despite the potentiality in early diagnosis, the application of advanced methodologies is constrained by costs, and the majority of detected biomarkers have not yet been validated by standardized routine assays. We are currently working on the validation of our findings by implementing low-throughput and low-cost methods.

Editorial acknowledgement

Clinical trial identification

NCT04781062 study start: 2021-01-19.

Legal entity responsible for the study

IRCCS Ospedale Policlinico San Martino.

Funding

AIRC - Italian Foundation for Cancer Research.

Disclosure

All authors have declared no conflicts of interest.