黃其晟1 塗昭江1 張景年1 張偉嶠2 1天主教輔仁大學附設醫院 乳房外科 2台北醫學大學 藥學系 基因表現圖譜與功能性分析顯示乙一型整合素 (ITGB1)是三重陰性乳癌的潛在性預後標記 Gene expression profiling combined with functional analysis identify integrin beta1 (ITGB1) as a potential prognosis biomarker in triple negative breast cancer 黃其晟1 塗昭江1 張景年1 張偉嶠2 1天主教輔仁大學附設醫院 乳房外科 2台北醫學大學 藥學系

Introduction Triple negative breast cancer (TNBC) accounts for approximately 15-20% of all types of breast cancer, and treatment is still limited. This type of breast cancer shows a high risk of recurrence, visceral metastasis, a worse prognosis, and shorter distant metastasis-free survival. Several studies have been reported that genetics factors are associated with breast cancer disease progression and patients' survival.

TNBC Migration Biomed Res Int. 2014;2014:536591 PIK3R3, ITGB1, ITGAL, and ITGA6 involved in the regulation of actin cytoskeleton

ITGB1, SOC Channel High ITGB1 expression in ovarian, lung, colon, prostate cancer. Regulate cell migration and invasion Activating EMT process (in gall bladder cancer) Targeted by miRNA 9-3p in claudin-low BC Calcium regulates cell migration Calcium influx through Store-operated calcium channel STIM1 and Orai1 Physiol Rev. 2015;95:1383-436.

Materials and methods We combined Taiwanese microarray data from the GEO database and The Cancer Genome Atlas (TCGA) database to study the role of Integrin Beta1 (ITGB1) in TNBC. Two triple negative breast cancer cell lines (MDA-MB-231; MDA- MB-468) were used to validate the functions of ITGB1.

Results We found that a higher ITGB1 gene expression level was associated to lower survival. Silencing of ITGB1 inhibited TNBC cell migration, invasion and store-operated calcium influx.

Taiwanese BC GSE53752 Early (stage I and II, n=37) vs. late (stage III and IV, n=14)

MDA-MB231 Cell Lines Transfected with SiControl and SiITGB1 qPCR for mRNA and Western blot for protein expression

MDA-MB231 Migration and Invasion Wound healing assay Migration calculated by ImageJ

MDA-MB231 Invasion Matrigel-coated transwell cell culture Quantification of cell invasion by phase-contrast microscopy

Store-operated Calcium Channel Thapsigargin to open the SOC channel

MDA-MB468 MDA-MB231: basal-B, highly invasive MDA-MB468: basal-A, weakly invasive

TCGA TNBC

Discussion Knockdown of ITGB1 inhibits TNBC migration and invasion Knockdown of ITGB1 reduces calcium influx through SOC channel High ITGB1 correlated to lower survival in Taiwanese TNBC

Conclusion Our study provided a potential candidate biomarker for breast cancer cells migration, invasion and TNBC patients' survival.