High CTLA-4 gene expression is an independent good prognosis factor in breast cancer patients, especially in the HER2-enriched subtype

CTLA-4 基因高表达是乳腺癌患者(尤其是 HER2 富集亚型)的独立良好预后因素

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作者:Yoel G Montoyo-Pujol, José J Ponce, Silvia Delgado-García, Tina A Martín, Hortensia Ballester, Elena Castellón-Molla, Angela Ramos-Montoya, Inmaculada Lozano-Cubo, J Miguel Sempere-Ortells, Gloria Peiró0

Background

Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-related death worldwide. This heterogeneous disease has been historically considered a non-immunogenic type of cancer. However, recent advances in immunotherapy have increased the interest in knowing the role of the immune checkpoints (IC) and other immune regulation pathways in this neoplasia.

Conclusion

Considering all these data, we can conclude that the expression of immunoregulatory genes depends on tumor phenotype and has potential clinical implications in BC patients.

Methods

In this retrospective study, we evaluated the correlation of mRNA expression of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), PDCD1LG2 (PD-L2), CD276 (B7-H3), JAK2, and FOXO1 with clinicopathological factors and BC patient's outcome by real-time quantitative polymerase chain reaction (qPCR).

Results

Our results showed that immunoregulatory gene expression depends on BC immunophenotype being CTLA-4 and PDCD1 (PD1) overexpressed on triple-negative/basal-like (TN/BL) and luminal B/HER2-positive phenotypes, respectively, and CD276 (B7-H3), JAK2 and FOXO1 associated with both luminal A and luminal B/HER2-negative tumors. In addition, we found that these genes can also be related to aggressive and non-aggressive clinicopathological characteristics in BC. Finally, survival analysis showed that CTLA-4 expression levels emerge as a significant independent factor of good prognosis in BC patients, especially in the HER2-enriched subtype.

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