Characteristics of the nested case-control studies included in this meta-analysis.

<p>M,male; F,female; T, storage temperature; RIA, radioimmunoassay assay; IRMA, immunoradiometric assay; ELISA, enzyme-linked immunoabsorbent assay; BMI,body mass index.</p

Sensitivity to CP treatment in SCLC cell line.

<p><b>(a)</b> Cells were starved for 12h and stimulated with 6.5nM IGF-1 for 10min. p-IGF-1R, t-IGF-1R, p-ERK, t-ERK, p-AKT, t-AKT and GAPDH were detected by WB. <b>(b)</b> Cells were treated with 0.065nM, 0.65nM, and 6.5nM of CP for 48h with presence or absence of serum. Cell viability was tested through MTT. The number of viable cells following CP treatment was presented as percentage of untreated cells. We did each experiment for three times, and data were represented as mean±SEM. Statistical analysis: *P<0.05, **P<0.01, ***P<0.001.</p

Metformin had additive anti-tumor effect with CP to target SCLC.

<p><b>(a)</b> H446 cells were pre-treated with 3mM Metformin for 1h, and then 0.65nM CP was added with presence or absence of serum. MTT was conducted to test cell viability after 48h of incubation. The number of viable cells following treatment is presented as percentage of untreated cells. <b>(b)</b> After 12h starvation, cells were treated with or without 3mM of metformin for 1h, and then treated with 0.65nM CP for 10min. Cell lysates were analyzed for p-IGF-1R, t-IGF-1R, p-ERK, t-ERK and GAPDH via WB. <b>(c)</b> 3mM Metformin was added to cells for 1h, then 0.65nM CP was added for a series of time points. The expression level of IGF-1R and GAPDH were detected through WB. <b>(d)</b> ß-arr1 KD H446 cells were treated with 3mM metformin for 1h, and then incubated with 0.65nM CP for 24h. Levels of IGF-1R and GAPDH were detected via WB. We did each experiment for three times, and data were represented as mean±SEM. Statistical analysis: *P<0.05, **P<0.01, ***P<0.001.</p

Receiver operating characteristics analysis based on the model of 7 resected lymph nodes in Stage I, Stage II and Stage I and Stage II results with OS as end point.

<p>In this model, the area under the curve (AUC) was 0.537, 0.586 and 0.719, respectively.</p

Survival curves of the new predictor (nLNs combined with tumor size).

<p>(A) Overall survival curves of the new predictor (<i>p</i><0.001). (B) Disease free survival curves of the new predictor (<i>p</i><0.001).</p

Flow chart of the cohort selection.

<p>Flow chart of the cohort selection.</p

Independent prognostic factor for OS and DFS by multivariate Cox regression analysis for the entire cohort of patients (n = 428).

<p>OS, overall survival; DFS, disease-free survival; HR, hazard ratio; 95% CI, 95% confidence interval; <i>p</i>, <i>p</i>-value; NS, not significant; nLNs, the number of resected lymph nodes;</p>*<p>variables, considering 65 as age cutoff and 3.5cm as cutoff for nLNs.</p

Flow diagram of included studies for this meta-analysis.

<p>Flow diagram of included studies for this meta-analysis.</p

Characteristics of patients and correlation between IGF-1R expression and clinic-pathological characters.

<p>Characteristics of patients and correlation between IGF-1R expression and clinic-pathological characters.</p

Characteristics of the case-control studies included in this meta-analysis.

<p>M,male; F,female; N,NSCLC; S,SCLC; T, storage temperature; RIA, radioimmunoassay assay; IRMA, immunoradiometric assay; ELISA, enzyme-linked immunoabsorbent assay; WLB, Western ligand blot.</p