Nuclear staining for TGF-βR2 and SMAD4 and association with overall survival.

<p>MST: median survival time; HR: hazard ratio; CI: confidence interval.</p><p>HR was adjusted for age, sex, race, stage and CA19-9.</p

MAF and functional significance of the SNPs investigated in the current study.

<p>MAF: minor allele frequency.</p><p>No variant allele was detected in the current study population.</p><p>“ = ” represents synonymous gene variants, i.e. no amino acid change.</p

Typical Immunohistochemical staining pattern for TGF-βR2 and SMAD4 in pancreatic adenocarcinoma tumor tissues.

<p>A: Positive nuclear expression of TGF-βR2 in a moderately differentiated ductal adenocarcinoma of the pancreas (Magnification: 10×40). B: Positive nuclear expression of SMAD4 in moderately differentiated ductal adenocarcinoma of the pancreas (Magnification: 10×40).</p

Plasma TGF-β1 level and overall survival.

<p>19.05 is the 25^th percentile of the TGF-β1 value of the entire study population.</p><p>HR was adjusted for age, sex, race, stage and CA19-9.</p

Genotype frequency and median survival time.

<p>SNPs that are conformed in HWE.</p

Overall survival of patients with various nuclear expression levels of TGF-βR2 and SMAD4.

<p>Nuclear staining score 0–1 is defined as low for TGF-βR2 and a score 0 as low for SMAD4. Red line: TGF-βR2 is high and SMAD4 is low (HL); black line: both high (HH); green line: both are low (LL); purple line: TGF-βR2 is low and SMAD4 is high (LH). The median survival times are 7.8, 8.6, 11.3, and 15.6 months for the HL, HH, LL and LH groups, respectively. Log-rank test P values and results of Cox regression analysis are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085942#pone-0085942-t002" target="_blank">Table 2</a>. Thus, TGFβ-R2/SMAD4 ratio may be prognostic, with low values corresponding with an improved survival.</p

Plot of overall survival curve in patients with all patients (A), patients with localized (B), locally advanced (C) or metastatic tumors by SMAD4 SNP rs2704733 genotype.

<p>Blue line: AA genotype; green line: AG/GG genotype. AA genotype was associated with an improved survival in the entire study population. On subgroup analysis, this survival difference was more relevant for advanced disease stage. P values by log-rank test are <0.0001, 0.369, 0.007, and 0.031 for panels A, B, C and D, respectively.</p

Characteristics of the patient population (n, %).

<p>Characteristics of the patient population (n, %).</p

Association of polygenic risk scores with chemotherapy-related neutropenia and taxane-related sensory neuropathy.

<p>Association of polygenic risk scores with chemotherapy-related neutropenia and taxane-related sensory neuropathy.</p

Kaplan-Meier plot comparing relapse-free survival in patients carrying >90 risk alleles to those carrying <80 risk alleles.

<p>Kaplan-Meier plot comparing relapse-free survival in patients carrying >90 risk alleles to those carrying <80 risk alleles.</p