C-Reactive Protein, Interleukin 6 and Lung Cancer Risk: A Meta-Analysis

<div><h3>Purpose</h3><p>Epidemiologic findings are inconsistent concerning the associations between C-reactive protein (CRP), interleukin 6 (IL-6) and lung cancer risk. We conducted a meta-analysis of epidemiologic studies to examine these associations.</p> <h3>Methods</h3><p>A systematic literature search up to October 2011 was performed in MEDLINE and EMBASE. Study-specific risk estimates were pooled using a random-effects model.</p> <h3>Results</h3><p>The 10 studies on CRP involved a total of 1918 lung cancer cases. The pooled RR of lung cancer for one unit change in natural logarithm (ln) CRP was 1.28 (95% CI 1.17–1.41). There was no statistically significant heterogeneity among studies (<em>P</em> = 0.116; I² = 36.6%). We also found that CRP was significantly associated with increased risk of lung cancer among men (RR 1.18, 95% CI 1.09–1.28) but not among women. The 5 studies on IL-6 involved a total of 924 lung cancer cases. The pooled RR of lung cancer for one unit change in ln IL-6 was 1.28 (95% CI 0.92–1.79), however, statistically significant heterogeneity was found. After excluding the study contributing most to the heterogeneity, the summary estimate was essentially unchanged.</p> <h3>Conclusion</h3><p>CRP was associated with increased risk of lung cancer, especially among men. There was no significant association between IL-6 and lung cancer risk.</p> </div

Summary risk estimates of the association between ln CRP and lung cancer risk.

<p>Abbreviation: RR, relative risk; CI, confidence intervals; ELISA, enzyme-linked immunosorbent assay.</p>†<p><i>I²</i> is interpreted as the proportion of total variation across studies that are due to heterogeneity rather than chance.</p

Characteristics of studies on IL-6 and lung cancer risk.

<p>Abbreviation: RR, relative risk; CI, confidence intervals; IL-6, Interleukin 6; NCC, nested case-control; Co, cohort; HABCS, Health Aging and Body Composition study; BWHHS, British Women’s Heart and Health Study; CCS, Caerphilly Cohort Study; NCI-MD, National Cancer Institute-Maryland; PLCO, prospective Prostate, Lung, Colorectal, and Ovarian.</p

Flow diagram of study identification.

<p>Flow diagram of study identification.</p

In studies on IL-6, risk estimates of lung cancer associated with one unit change in ln IL-6.

<p>Squares indicate study-specific risk estimates (size of the square reflects the study-specific statistical weight, i.e., the inverse of the variance); horizontal lines indicate 95% confidence intervals (CIs); diamonds indicate summary risk estimate with its corresponding 95% confidence interval. Abbreviation: BWHHS, British Women’s Heart and Health Study; CCS, Caerphilly Cohort Study; NCI-MD, National Cancer Institute-Maryland; PLCO, prospective Prostate, Lung, Colorectal, and Ovarian.</p

In studies on CRP, risk estimates of lung cancer associated with one unit change in ln CRP.

<p>Squares indicate study-specific risk estimates (size of the square reflects the study-specific statistical weight, i.e., the inverse of the variance); horizontal lines indicate 95% confidence intervals (CIs); diamonds indicate summary risk estimate with its corresponding 95% confidence interval. Abbreviation: BWHHS, British Women’s Heart and Health Study; CCS, Caerphilly Cohort Study.</p

Effects of miR-125b on cell invasion in MCF-7 and MDA-MB-231 in vitro.

<p>(A) Photographs of the cell invasion through the polycarbonate membrane stain by crystal violet. The migratory cell numbers of both cell lines transfected with miR-125b mimics were significantly more than that of cells transfected with inhibitor respectively. (B) OD570 of stain crystal violet. Data were present as mean ± SEM, n = 3, *p<0.05, **p<0.01 vs. NC group. (C) Real-time PCR analysis of the expression of miR-125b with transfected miR-125b-mimics, miR-125b inhibitors, NC and untranfected one in MCF-7 and MDA-MB-231 cells. −ΔΔCt = − (Ctx-CtU6x)-(CtNCx-CtU6_NC). Data were present as mean ± SEM, n = 3, **P<0.01 vs. NC group in MCF-7, ^##P<0.01 vs. NC group in MDA-MB-231.</p

Effects of miR-125b on vimentin and α-SMA expression in MCF-7/ADR and MDA-MB-231 with ROCK inhibitor <i>in vitro</i>.

<p>(A B) Effects of miR-125b and Y-27632 on α-SMA and Vimentin expression. MCF-7/ADR and MDA-MB-231 cells were transfected with miR-125bmimics or control RNA respectively. After 24 h, cells were incubated with or without Y-27632; after 72 h, α-SMA protein, vimentin and β-actin were detected by western blot. (C D) Quantitative data of densitometric analyses. The ratio of α-SMA protein to β-actin were present as mean ± SEM, n = 3, *p<0.05, vs. NC group of α-SMA expression ^#p<0.05, vs. group of cotransfected with miR-125b and Y-27632 of α-SMA expression.</p

Effects of miR-125b on breast tumor metastasis in vivo.

<p>(A) Photographs of diagnosed tumor metastasis by NIR-imaging system, 3 weeks after injection breast cancer cells MCF-7 and MCF-7-125b NIR probe Folate-Polyethylene Glycol was injected to BALB/c nude mice and formation of imaged at 0 h and 4 h after injection of NIR-probe. (B) Images of metastatic focuses in patho-histological examination stained with H&E. (C) Images of representative liver dissected from mouse and patho-histological examination stained with H&E.</p

miR-125b directly target STARD13 mRNA.

<p>(A) MiR-125b directly target human STARD13. (A) The miR-125b targets on STARD13 were predicted using Targetscan 5.1. (A) pMiR-Report vectors containing the wt or mut miR-125b binding site from the 3′UTR of STARD13 mRNA, and miR-125b-mimics or NC, as well as an expression cassette for Rluc were co-transfected into HEK-293T cells. Two days later Fluc activity in cells was measured and normalized to Rluc activities two days after. Data were present as the mean ± SEM, n = 3, *p<0.05 vs. NC group. (C) Breast cancer cell lines of MCF-7 and MDA-MB-231 cells were transfected with miR-mimics, miR-125b-inhibitors and control miRNA, the gene expression of STARD13 was detected by real-time RT-PCR after 48 h. Data were present as the mean ± SEM, n = 3 ^ΔΔp<0.001 NC group in MDA-MB-231 vs. NC group in MCF-7; (D) Breast cancer cell lines of MCF-7 and MDA-MB-231 cells were transfected with miR-mimics, miR-125b-inhibitors and control miRNA, STARD13 protein and β-actin after 72 h were detected by western blot. (E) Quantitative data of densitometric analyses. The ratio of STARD13 protein and mRNA levels to β-actin and GAPDH were displayed as mean ± SEM, n = 3, *p<0.05, **p<0.01 vs. NC group; ^ΔΔp<0.001 NC group in MDA-MB-231 vs. NC group in MCF-7.</p