Combining PET/CT with serum tumor markers to improve the evaluation of histological type of suspicious lung cancers

<div><p>Objective</p><p>Histological type is important for determining the management of patients with suspicious lung cancers. In this study, PET/CT combined with serum tumor markers were used to evaluate the histological type of lung lesions.</p><p>Materials and methods</p><p>Patients with suspicious lung cancers underwent ¹⁸F-FDG PET/CT and serum tumor markers detection. SUVmax of the tumor and serum levels of tumor markers were acquired. Differences in SUVmax and serum levels of tumor markers among different histological types of lung cancers and between EGFR mutation statues of adenocarcinoma were compared. The diagnostic efficiencies of SUVmax alone, each serum tumor marker alone, combined tumor markers and the combination of both methods were further assessed and compared.</p><p>Results</p><p>SCC had the highest level of SUVmax, followed by SCLC and adenocarcinoma, and benign lesions had a lowest level. CYFRA21-1 and SCC-Ag were significantly higher in SCC, NSE was significantly higher in SCLC (P<0.001), and CEA was higher in adenocarcinoma (P = 0.343). The diagnostic efficiencies in evaluating histological types of suspicious lung cancers were insufficient when using each serum tumor marker or SUVmax alone. When combined, the AUC, sensitivity and specificity increased significantly (P<0.05 for all). Additionally, to adenocarcinoma, no significant difference was found between EGFR mutation statuses in SUVmax or serum tumor markers (P>0.05 for all).</p><p>Conclusions</p><p>SUVmax and serum tumor markers show values in evaluating the histological types of suspicious lung cancers. When properly combined, the diagnostic efficiency can increase significantly.</p></div

Additional file 1: of LAIT: a local ancestry inference toolkit

Simulation details of comparison analysis. (DOCX 14 kb

Lentivirus-mediated FGFR1 overexpression in A549 cells significantly decreased influenza A virus replication.

<p>A549 cells were infected with recombinant lentivirus expressing FGFR1, FGFR4, or GFP (as a control). After 48 h, A549 cells were infected with PR8 virus (MOI = 1). The supernatants and lysates of A549 cells were harvested after 24 h virus infection. (<b>A</b>, <b>B</b>) Influenza M1 mRNA levels in A549 cells with PR8 and H5N1 were detected using real-time PCR. (<b>C</b>, <b>D</b>) Progeny virus titers of PR8 and H5N1 were determined as described previously. (<b>E</b>, <b>F</b>) FGFR1 and FGFR4 expression efficiencies were detected using real-time PCR and Western blotting. All graphs present the means ± s.e.m. (n = 3). Values of P<0.05 * were considered statistically significant and P<0.001 *** statistically highly significant.</p

Statistical values of all metrics for differentiating between lung cancers and benign lesions and NSCLC and SCLC.

<p>Statistical values of all metrics for differentiating between lung cancers and benign lesions and NSCLC and SCLC.</p

FGFR1 silencing by RNAi increased influenza A/PR8 and H5N1 virus replication.

<p>(<b>A</b>-<b>D</b>) A549 cells were transiently transfected with specific siRNA targeting FGFR1, FGFR4, or negative control siRNA. Forty-eight hours later, A549 cells were infected with PR8 virus at an MOI of 1. The cell culture supernatants and cell lysates were obtained at 24 hpi. Influenza virus M1 mRNA expression in A549 cells with PR8 (<b>A</b>) or H5N1 (<b>B</b>) infection was detected using real-time PCR. Progeny virus titers of PR8 (<b>C</b>) or H5N1 (<b>D</b>) were determined using MDCK cells with the TCID₅₀ assay. (<b>E</b>) The knockdown efficiencies of FGFR1 and FGFR4 by target siRNA were tested using real-time PCR. (<b>F</b>) Protein expressions of FGFR1 and FGFR4 were detected using specific antibodies by Western blotting assay. All graphs represent the means ± s.e.m. (n = 3). Values of P<0.01 **and P<0.001 *** were considered statistically highly significant.</p

Descriptive statistics for 201 study patients.

<p>Descriptive statistics for 201 study patients.</p

Specific siRNA target FGFR1 markedly increased PR8 virus entry at an early stage of the viral life cycle.

<p>(<b>A</b>-<b>C</b>) A549 cells were transfected with FGFR1 siRNA#1, FGFR4 siRNA#1, and negative control siRNA. After 48 h of transduction, A549 cells were incubated with PR8 virus at an MOI of 0.01 for 4 h, followed by indirect immunofluorescence assays. A549 cells were stained with anti-influenza A virus NP antibodies (green) and Hoechst 33342 (nucleus, blue). (<b>D</b>) The data of PR8-infected cells were presented as the percentages of NP-positive cells to the total number of cells. The bars represent the means ± s.e.m. (n = 3). P<0.001 *** were considered statistically highly significant.</p

Differences in SUVmax and serum tumor markers among different histological types.

<p>Differences in SUVmax and serum tumor markers among different histological types.</p

Differences in SUVmax and serum tumor markers between different EGFR mutation statues.

<p>Differences in SUVmax and serum tumor markers between different EGFR mutation statues.</p

Primer pairs used for real-time PCR.

<p>Primer pairs of human <i>FGFR1</i>, <i>FGFR2</i>, <i>FGFR3</i>, <i>FGFR4</i>, influenza virus <i>M1</i>, and <i>GAPDH</i> were designed using Primer 5.0 and presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124651#pone.0124651.t001" target="_blank">Table 1</a>.</p><p>Primer pairs used for real-time PCR.</p