S100A11 expression levels in adenocarcinomas with KRAS mutations and proliferating activity.

<p>The thickened lines indicate the median score of S100 A11 expression, which was 1.00 in KRAS Wild-type/Ki-67 Low cases (n = 94), 1.50 in KRAS Wild-type/Ki-67 High cases (n = 62), 1.20 in KRAS Mutated-type/Ki-67 Low cases (n = 11) and 1.80 in KRAS Mutated-type/Ki-67 High cases (n = 11). S100A11 expression levels were significantly higher in adenocarcinomas with KRAS mutations and strong proliferating activity (P = 0.038 in the Kruskal-Wallis test). Wt, Wild-type; Mt, Mutated-type.</p

Relationship between S100A11 expression and clinicopathologic characteristics of stage I lung adenocarcinomas.

<p>No., number of cases; WEL, well differentiated; MOD, moderately differentiated; POR, poorly differentiated carcinomas; AIS, adenocarcinoma in situ; MIA, minimally invasive adenocarcinoma; LEP, lepidic predominant; ACN, acinar predominant; PAP, papillary predominant, SOL, solid predominant; MUC, invasive mucinous adenocarcinoma.</p><p>Histologic subtypes were classified according to the 2011 IASLC/ ATS/ETS classification of lung adenocarcinoma.</p><p>P, significant level for Mann-Whitney or Kruskal-Wallis test.</p><p>Relationship between S100A11 expression and clinicopathologic characteristics of stage I lung adenocarcinomas.</p

The S100A11 and S100A2 expression levels in all tumors.

<p>Median expression scores were 1.30 in S100A11 (A) and 0.10 in S100A2 (B). S100A11 was not expressed in 8 cases (A), while S100A2 was not expressed in nearly half of the cases examined (83 cases) (B). ADC, Adenocarcinoma.</p

Kaplan-Meier Disease-free survival curves by S100A11 expression levels for stage I lung adenocarcinomas.

<p>Five-year disease-free survival rates were 76.3% in high-S100A11 expressers (n = 61) and 90.1% in low-S100A11 expressers (n = 118). The strong expression of S100A11 correlated with shorter disease-free survival in post-operative lung adenocarcinomas (p = 0.0182 in the Log-rank test).</p

Multiple linear regression analysis of relationships between S100A11 expression and clinicopathologic characteristics of stage I lung adenocarcinomas.

<p>WEL, well differentiated; MOD, moderately differentiated; POR, poorly differentiated carcinomas.</p><p>Histologic subtypes were excluded from factors due to the strong correlation that existed with histologic grade (Spearman’s coefficient 0.567, P<0.001).</p><p>Multiple linear regression analysis of relationships between S100A11 expression and clinicopathologic characteristics of stage I lung adenocarcinomas.</p

Downstream targets up-regulated by oncogenic KRAS with gene chip microarray analysis.

<p>Accession, gene bank accession number; Map, chromosome locus; MOCK, mock-transduced NHBE-T; G12, wild-type KRAS-transduced NHEB-T; V12, oncogenic mutant KRAS-transduced NHBE-T.</p><p>Flags indicate whether gene expression was present (P) or absent (A). Genes whose signal values were more than 20-fold higher in KRAS/V12 cells than in mock- and/or KRAS/G12 cells are extracted from our date of a gene chip microarray analysis previously described [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142642#pone.0142642.ref007" target="_blank">7</a>]. The genes sorted are listed in this table.</p><p>Downstream targets up-regulated by oncogenic KRAS with gene chip microarray analysis.</p

Downstream targets up-regulated by oncogenic KRAS with proteomic analysis.

<p>Accession, gene bank accession number; Map, chromosome locus; MOCK, mock-transduced NHBE-T; G12, wild-type KRAS-transduced NHEB-T; V12, oncogenic mutant KRAS-transduced NHBE-T.</p><p>Proteins whose signal intensities were more than 2-fold higher in KRAS/V12 cells than in mock- and/or KRAS/G12 cells are extracted from our date of a comprehensive proteomic analysis previously described [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142642#pone.0142642.ref008" target="_blank">8</a>]. The proteins sorted are listed in this table.</p><p>Downstream targets up-regulated by oncogenic KRAS with proteomic analysis.</p

Immunohistochemical examination of S100A11 and S100A2 protein expression levels in tumors and non-tumorous epithelia from lung adenocarcinoma (ADC) patients undergoing surgical resection.

<p>Representative photographs from normal bronchioles (A, E) and tumors, in which the expression of S100A11 and S100A2 was negative (B, F), weak (C, G) and strong (D, H), are shown.</p

Representative histological appearances of the biopsy specimens (A, <i>EGFR</i>-mutated lung adenocarcinoma (LADC); B, <i>EGFR</i> wild-type LADC).

<p>The micropapillary element, which is composed of papillary structures lacking fibrovascular cores, floats in alveolar spaces (A, hematoxylin and eosin (HE) stain, ×200). The acinar element (and some crush artifacts) grows in collapse fibrosis (B, HE stain, ×200).</p

Kaplan-Meier recurrence-free survival curves of the association between the proportion of micropapillary (mPAP) element and disease recurrence in patients with stage I <i>EGFR</i>-mutated lung adenocarcinomas.

<p>A, tumors in which the mPAP element accounted for ≥5% of the tumor versus (vs) those in which the mPAP element accounted for <5% of the tumor (<i>P</i> = 0.028 in the Log-rank test); B, tumors in which the mPAP element accounted for ≥10% of the tumor vs those in which the mPAP element accounted for <10% of the tumor (<i>P</i> = 0.005 in the Log-rank test); C, tumors in which the mPAP element accounted for ≥20% of the tumor vs those in which the mPAP element accounted for <20% of the tumor (<i>P</i> = 0.102 in the Log-rank test); n, number of tumors examined; asterisk(*), statistically significant.</p