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Table 1 Protein signal pathway correlates of breast pCR

From: Pathologic complete response after preoperative anti-HER2 therapy correlates with alterations in PTEN, FOXO, phosphorylated Stat5, and autophagy protein signaling

Analyte Treatment arm (Baseline/Day 14) Reverse phase protein microarray results Interpretation
pCR Breast Yes pCR p Value <0.05
Breast No
EGFR Tyr1068 Lapatinib arm Baseline Mean: Mean: p = 0.02c Phosphorylation of EGFR at Tyrosine 1068 occurs during receptor activation, leading to downstream activation of growth and pro-survival pathway proteins.
-0.66 -0.01
(n = 6) (n = 11)
FOXO1/03A Ratios All treatment arms Baseline     FOXO is a transcription factor that functions as a tumor suppressor. FOXO triggers cell cycle arrest and apoptosis after it enters the nucleus. Phosphorylation of FOXO (pFOXO) causes export from the nucleus and inactivates its tumor suppressor function. Trastuzumab inhibits HER2+ cells by reactivation of FOXO1A [15]
pPTEN:pFOXO   Mean ratio: 2.79 Mean ratio: 0.04 p = 0.01b
(n = 27) (n = 22)
PI3K:pFOXO   Mean ratio: 3.23 (n = 27) Mean ratio p = 0.039
-0.2 (n = 22)
pStat5 Tyr694 Trastuzumab arm day 14 Mean: Mean: p = 0.017b Stat5 is a transcription factor. After phosphorylation by JAK2, pStat5 translocates to the nucleus to initiate transcription of e-cadherin, which promotes homotypic adherence between breast cells and basement membrane, i.e., normal behavior. Absent nuclear pStat5 is a negative prognostic factor [16, 17]. Increased pStat indicates transcription functionality in our pCR subjects.
1.14 -0.49
(n = 11) (n = 9)
Protein linkage correlation analysisa All treatment arms Baseline     Autophagy is a normal cellular process to promote cell survival under stress (hypoxia, nutrient deprivation, loss of adhesion). Autophagy allows the cell to “self eat” to generate ATP from cellular contents and thereby survive in times of stress, starvation, hypoxia, or chemotherapy. Autophagy is regulated by a network of cell signaling proteins, including mTOR, Beclin (upstream markers), Bcl2, LC3B (downstream markers), Atg5. Cells from patients classified as pCR No appear to engage autophagy to survive in the presence of treatment with trastuzumab, lapatinib or the combination [18].
LC3B-Beclin    LC3B-Beclin 1 SR = 0.88 p < 0.001
LC3B-MMP14    LC3B-MMP14 p < 0.001
SR = 0.83
LC3B-Her2   LC3B-HER2   p < 0.001
SRa = 0.88
LC3B-Stat5 Tyr694   LC3B-pStat5   p < 0.001
SR = 0.84
  1. aNonparametric Spearman’s rho (SR) correlation coefficient; bWilcoxon rank sum; cTwo sample t-test.