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A Next-generation Tissue Microarray ngTMA Protocol for Biomarker Studies
Published on: September 23, 2014
ITGB2 Gene Gain as a Prognostic Marker for Early Recurrence in Luminal HER2-Negative High Proliferative Breast Cancer
Chun-Yu Liu1,2,3, Ji-Lin Chen1,2, Yi-Fang Tsai1,2,4
1School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Purpose:
Early recurrence reflects aggressive disease and poor prognosis, with patterns varying across breast cancer subtypes. Early recurrence is a major challenge in luminal HER2-negative high proliferative breast cancer, yet reliable biomarkers remain limited. Identifying biomarkers associated with early recurrence is therefore of significant interest.
Materials And Methods:
Forty-two patients with stage I-III luminal HER2-negative, high-proliferative breast cancer were enrolled in the VGHTPE cohort and underwent targeted next-generation sequencing using the ACTOnco Comprehensive Cancer Panel. Findings were validated in The Cancer Genome Atlas (TCGA) and METABRIC datasets, and in vitro experiments were conducted to assess cell aggressiveness.
Results:
We examined 42 patients, including 15 who experienced recurrence within five years and 27 who did not. Next-generation sequencing revealed that the most prevalent alterations in this luminal HER2-negative, high-proliferative breast cancer cohort were mutations in PIK3CA and TP53, and amplifications/gains in MCL1, MYC, and KLF6. Patients with recurrence within five years exhibited a higher frequency of ITGB2 gain compared with non-recurrent patients. Validation in the TCGA and METABRIC cohorts confirmed the prognostic significance of ITGB2 gain in ER+/HER2- breast cancers. Gene Set Enrichment Analysis indicated that high ITGB2 expression was enriched in KRAS and EMT pathways. In vitro experiments further demonstrated that ITGB2 knockdown led to inactivation of Akt and ERK signaling and suppression of cell aggressiveness in ER+/HER2- breast cancer cells.
Conclusion:
ITGB2 gain represents an unfavorable prognostic marker for early recurrence in luminal HER2-negative high proliferative breast cancer, with potential therapeutic implications.
