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. 2023 Dec;20(4):240-250.
doi: 10.5114/kitp.2023.134177. Epub 2024 Jan 11.

A systematic review and meta-analysis to evaluate blood levels of interleukin-6 in lung cancer patients

Seyed Vahid Jasemi  1 , Soha Zia  2 , Seyed Ghasem Mirbahari  3 , Masoud Sadeghi  4
Affiliations

A systematic review and meta-analysis to evaluate blood levels of interleukin-6 in lung cancer patients

Seyed Vahid Jasemi et al. Kardiochir Torakochirurgia Pol. 2023 Dec.

Abstract

Introduction: The exact mechanism responsible for inflammation in malignancy is not completely understood, but it is possible that interleukin-6 (IL-6) plays a major role in triggering and maintaining an inflammatory response.

Aim: To conduct a systematic review and meta-analysis of the levels of IL-6 in the serum/plasma of lung cancer (LC) patients.

Material and methods: The researchers searched four databases up to September 11, 2022, to find studies that reported on IL-6 levels in LC patients compared to healthy controls (HCs). They calculated effect sizes using standardized mean difference (SMD) with a 95% confidence interval (CI). To evaluate the quality of each study, they used the Newcastle-Ottawa Scale (NOS). They performed subgroup analysis, sensitivity analysis, meta-regression analysis, heterogeneity analyses, trial sequential analysis, and publication bias with the trim-and-fill method.

Results: The meta-analysis included 28 studies, and the results showed that the pooled SMD was 1.71 (95% CI: 1.22, 2.19; p < 0.00001; I2 = 98%), indicating that LC patients had significantly higher levels of IL-6 in their serum/plasma than HCs.

Conclusions: The study found that the publication year and quality score of the studies were positively associated with the level of IL-6, while the sample size was inversely related. The research suggests that measuring IL-6 levels in the blood could be useful for detecting and monitoring LC as it appears to be a reliable biomarker.

Keywords: interleukin-6; lung neoplasm; meta-analysis; plasma; serum.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the study selection interleukin-6 *15 studies reported polymorphisms of IL-6. 1 study reported IL-6 mRNA level. 44 studies didn’t include control group or participants were under treatment. 1 study included individuals with several cancers as case group. 1 study measured sputum IL-6. 1 study reported the levels of IL-6 in bronchoalveolar lavage fluid. 1 study reported the levels of IL-6 in breath condensate. 5 studies didn’t include required data for case and/or control groups. 1 study had duplicate data. 2 studies had no full text. 1 study reported fluorescence intensity of IL-6. 1 study reported production of IL-6 by peripheral blood monocytes. 1 study reported geometric means of IL-6. 1 study had irrelevant data.
Figure 2
Figure 2
Random-effects forest plot analysis. Comparison of blood interleukin-6 levels in lung cancer patients compared to healthy controls
Figure 3
Figure 3
Trial sequential analysis. Comparison of blood interleukin-6 levels in lung cancer patients compared to healthy controls. (heterogeneity or D2 = 100%)
Figure 4
Figure 4
Heterogeneity plots. A – Radial plot. B – L’Abbe plot. Numbers show studies
Figure 5
Figure 5
Sensitivity analyses: A – one-study-removed analysis. B – cumulative analysis
Figure 6
Figure 6
Funnel plot and trim-and-fill method. The open dots show the observed studies, and the closed dots show the missing studies imputed by the trim-and-fill method. The dashed lines that create a triangular area indicate the 95% confidence intervals, and the vertical solid line illustrates the overall effect size
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