26P - Liquid biopsy-based percision immunotherapy: CCAT1 and HEIH lncRNAs identify young breast cancer patients likely to respond to PD-L1 blockade

Background

Young breast cancer (BC) patients frequently exhibit aggressive characteristics such as high rates of metastases, high immune evasion and intricate therapy resistance. Recently, this group has demonstrated elevated resistance to PD-1/PD-L1 immune checkpoint inhibitors, prompting concerns regarding the effectiveness of existing treatment approaches. So, understanding the molecular processes underlying these patients' resistance to immunotherapy is critical for improving treatment selection and effectiveness. Long non-coding RNAs (LncRNAs) has recently been reported to act as immuno-modulators of BC cells. Consequently, making them potentially useful as cancer-immune biomarkers for determining treatment regimen. In BC, these lncRNAs were found to oncogenic lncRNAs and have a positive correlation with increased expression of PD-L1. Thus, our goal is to explore if these lncRNAs can serve as a non-invasive biomarker for the identification of young BC patients who are more likely to be responsive to PD-L1 inhibitors, hence assisting in the formulation of treatment decisions.

Methods

Breast tissues and serum samples were obtained from BC patients (n=40). Total RNA was isolated and extracted from serum and tissue samples and quantified via qRT-PCR. Bioinformatics and survival analysis data regarding breast cancer were gathered and retrieved from the TCGA database and by using KM plotter respectively (https://kmplot.com/analysis/).

Results

PD-L1, CCAT-1 and HEIH expression levels were considerably higher in BC tissues and serum. Young BC patients had significantly greater expression of lncRNAs compared to older patients in tissues and serum samples. TNM plot showed significant upregulation of CCAT1 in basal subtype and significant downregulation of HEIH in basal subtype. In Basal BC patients, survival study using the Kaplan-Meier plotter showed that CCAT-1 overexpression was related with lower overall survival. In contrast, HEIH overexpression was associated with higher overall survival rates.

Conclusions

CCAT1 and HEIH are novel non-invasive biomarkers that could serve as valuable predictive biomarkers to guide treatment decisions in this high-risk patient population.

Legal entity responsible for the study

The authors.

Funding

L'Oreal-UNESCO for women in science.

Disclosure

All authors have declared no conflicts of interest.