Biology subjects

Liyanage, C.

Publications and source records attributed to Liyanage, C..

2 recordsLinked to original sources

bioRxiv2023

The circulating immune cell landscape stratifies metastatic burden in breast cancer patients

Advanced breast cancers show varying degrees of metastasis; however, reliable biomarkers of metastatic disease progression remain unknown. In circulation, immune cells are the first line of defence against tumour cells. Herein, using >109,591 peripheral blood mononuclear cells from healthy individuals and breast cancer patients, we tested whether molecular traits of the circulating immune cells, probed with single-cell transcriptomics, can be used to segregate metastatic profiles. Our analyses revealed significant compositional and transcriptional differences in PBMCs of patients with restricted or high metastatic burden versus healthy subjects. The abundance of T cell and monocyte subtypes segregated cancer patients from healthy individuals, while memory and unconventional T cells were enriched in low metastatic burden disease. The cell communication axes were also found to be tightly associated with the extent of metastatic burden. Additionally, we identified a PBMC-derived metastatic gene signature capable of discerning metastatic condition from a healthy state. Our study provides unique molecular insights into the peripheral immune system operating in metastatic breast cancer, revealing potential new biomarkers of the extent of the metastatic state. Tracking such immune traits associated with metastatic spread could complement existing diagnostic tools.

cancer biology↗

bioRxiv2023

Identification of a Micropeptide Linked to Cancer Stem Cell Regulation and Chemoresistance

Short open reading frames encoding micropeptides (miPEPs) less than 100 amino acids in length have recently emerged as important regulators of diverse biological functions. However, the functional role of cancer-specific miPEPs in cancer progression and therapeutic response remains largely unexplored. Genome-wide association studies have identified an association of Iroquois (IRX) clusters with multiple cancer risk. In this study, we identified 17 miPEPs generated from IRX clusters in prostate, breast, endometrial, and ovarian cancers using SWATH-MS/MS-based proteomic analysis. We found that IRX4-derived miPEP, IRX4_PEP1, promotes prostate cancer (PCa) cell proliferation, migration, and invasion by interacting with heterogeneous nuclear ribonucleoprotein K (hnRNPK). Overexpression of IRX4_PEP1 leads to dysregulation of stem cell pathways by co-interaction with Catenin beta-1 (CTNB1) and upregulation of prominent PCa stem markers, resulting in docetaxel resistance in PCa. IRX4_PEP1 expression is significantly upregulated in prostate tumour tissues compared to normal and is positively correlated with disease aggressiveness. SIGNIFICANCEOur findings highlight the critical role of IRX4_PEP1 in regulating PCa stem cells and chemotherapy resistance and suggest it as a novel therapeutic target for the treatment of PCa. Moreover, IRX4_PEP1 expression can serve as a novel potential diagnostic and prognostic biomarker for PCa.

cancer biology↗