Single‐Cell Transcriptome Analysis Uncovers La Ribonucleoprotein 6 (LARP6) as a Dual Regulator of Proliferation and Immune Infiltration in Triple‐Negative Breast Cancer

TL;DR

This study identifies LARP6 as a key gene linked to both cancer growth and immune response in aggressive triple-negative breast cancer.

Contribution

LARP6 is newly identified as a dual regulator of proliferation and immune infiltration in TNBC through single-cell transcriptome analysis.

Findings

LARP6 is significantly upregulated in TNBC compared to other breast cancer subtypes.

High LARP6 levels correlate with reduced patient survival and increased cancer cell proliferation.

LARP6 expression is associated with specific immune cell populations in the tumor microenvironment.

Abstract

Breast cancer is classified into multiple subtypes, including hormone receptor‐positive (oestrogen/progesterone receptor, ER/PR), HER2‐positive (human epidermal growth factor receptor 2), and triple‐negative breast cancer (TNBC). Among these, TNBC is more aggressive and susceptible to recurrence. The identification of novel TNBC‐specific markers is crucial for the development of advancing therapeutic approaches for this subtype. In our study, firstly we integrated single‐cell RNA sequencing data from more than 260,000 cells from previously published breast cancer datasets with ER‐positive, HER2‐positive and TNBC samples, determined the cell types based on the marker genes and identified the differentially expressed genes across various cell types between TNBC and ER/HER2‐positive cancers using pseudobulk analysis. Additionally, we conducted gene set enrichment analysis (GSEA) with the differentially expressed genes and identified 8 pathways which are consistent between the comparisons of TNBC/ER‐positive and TNBC/HER2‐positive. Furthermore, we found the shared gene, LARP6 (La Ribonucleoprotein 6) was significantly upregulated in TNBC compared to ER and HER2‐positive breast cancers. Also, the result from survival analysis revealed that the high LARP6 level significantly affected patient survival. At last, we found LARP6 was highly expressed in the TNBC cell line, and knockdown of LARP6 reduced cell proliferation, which was associated with the cell cycle alterations as determined by TriCycle analysis. Immune infiltration analysis further revealed that LARP6 expression correlates with distinct immune cell populations in the tumour microenvironment, suggesting its role beyond cancer cell intrinsic functions.

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