Prognostic and clinicopathological significance of serum interleukin-6 expression in colorectal cancer: a systematic review and meta-analysis

Wang, Zhen; Wu, Pin; Wu, Dang; Zhang, Zhigang; Hu, Guoming; Zhao, Shuai; Lai, Yucheng; Huang, Jian

doi:10.2147/ott.s93297

Cited by 18 publications

(19 citation statements)

References 47 publications

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“…[19][20][21][22] IL-6 levels are correlated with CRC development, tumor cell invasion, increased distant metastasis and decreased survival time. 23,24 In mouse models of CRC, ablation of IL-6 reduces tumor burden and increases survival time, suggesting it is a critical tumor-promoting factor. 25 The combination of TNF-a and IL-6 produces a synergistic response in CRC that promotes proliferation, survival and further cytokine production.…”

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confidence: 99%

“…IL‐1β signaling in many cell types, including epithelial cells, fibroblasts and infiltrating immune cells, results in production of IL‐6 and TNF‐α . IL‐6 levels are correlated with CRC development, tumor cell invasion, increased distant metastasis and decreased survival time . In mouse models of CRC, ablation of IL‐6 reduces tumor burden and increases survival time, suggesting it is a critical tumor‐promoting factor .…”

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confidence: 99%

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Inhibition of MK2 suppresses IL‐1β, IL‐6, and TNF‐α‐dependent colorectal cancer growth

Ray

Berggren

Cruz

et al. 2017

Intl Journal of Cancer

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Colorectal cancer (CRC) development and progression is associated with chronic inflammation. We have identified the MAPK-activated protein kinase 2 (MK2) pathway as a primary mediator of inflammation in CRC. MK2 signaling promotes production of proinflammatory cytokines IL-1β, IL-6 and TNF-α. These cytokines have been implicated in tumor growth, invasion and metastasis. For the first time, we investigate whether MK2 inhibition can improve outcome in two mouse models of CRC. In our azoxymethane/dextran sodium sulfate (AOM/DSS) model of colitis-associated CRC, MK2 inhibitor treatment eliminated murine tumor development. Using the implanted, syngeneic murine CRC cell line CT26, we observe significant tumor volume reduction following MK2 inhibition. Tumor cells treated with MK2 inhibitors produced 80% less IL-1β, IL-6 and TNF-α and demonstrated decreased invasion. Replenishment of downstream proinflammatory MK2-mediated cytokines (IL-1β, IL-6 and TNF-α) to tumors led to restoration of tumor proliferation and rapid tumor regrowth. These results demonstrate the importance of MK2 in driving proinflammatory cytokine production, its relevance to in vivo tumor proliferation and invasion. Inhibition of MK2 may represent an attractive therapeutic target to suppress tumor growth and progression in patients.

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confidence: 99%

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confidence: 99%

Inhibition of MK2 suppresses IL‐1β, IL‐6, and TNF‐α‐dependent colorectal cancer growth

Ray

Berggren

Cruz

et al. 2017

Intl Journal of Cancer

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“…IL-6, a pleiotropic pro-inflammatory Th2 cytokine, has been demonstrated by several studies to participate in tumor cell proliferation, apoptosis and angiogenesis (21,22). It was also reported that high IL-6 expression in patient plasma was associated with shorter OS in lung (23) and colorectal cancer (24). In addition, IL-6 alone was found to be significantly associated with PFS in the TG4010 study.…”

Section: Discussionmentioning

confidence: 89%

Elevated IL‑6/IL‑1Ra ratio as a prognostic biomarker of poor chemotherapy efficacy in Chinese patients with metastatic NSCLC, validated in a Caucasian patient cohort

Liu¹,

Sansas

Préville

et al. 2018

mol clin onc

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The treatment options for advanced (stage IV) non-small cell lung cancer (NSCLC) at diagnosis remain disappointing. The development of immunotherapeutic drugs may represent a promising alternative approach to the treatment of late-stage cancer at diagnosis. These current paradigms in cancer treatment highlight the need for new biomarkers related to the immune status of the patients and/or the tumor microenvironment, for immune as well as chemotherapeutic treatment options. The aim of the present study was to analyze soluble immune factors in patients with lung cancer treated with chemotherapy to identify prognostic biomarkers. For this purpose, the data obtained from two cohorts of patients from different clinical trials were analyzed: A Chinese patient cohort to identify potential prognostic biomarkers, and a validation cohort comprising patients with a similar clinical stage from a clinical trial in Europe. Analyses of soluble markers for inflammation and immune status were performed by standard assays and multiplex Luminex assays. Differences in overall survival (OS) and progression-free survival (PFS) were evaluated with the log-rank test and robustness was evaluated with the resampling approach. In the Chinese cohort, four prognostic biomarkers of poor response to chemotherapy were identified, which had a significant impact on OS and PFS. It was confirmed in the Caucasian validation cohort that an increased value of the interleukin (IL)-6/IL-1Ra cytokine ratio at inclusion was correlated with significantly shorter OS and PFS, whereas no other biomarkers were found to be significant. The IL-6/IL-1Ra ratio reflects the imbalance between pro-and anti-inflammatory status in the plasma of patients and may be associated with tumor inflammatory status and the therapeutic outcome. The present study highlights the identification of the IL-6/IL-1Ra ratio as a biomarker of poor prognosis in terms of response to chemotherapy in two independent clinical studies.

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“…Two cytokines with a more established prognostic role in colorectal cancer are IL-6 and IL-8 and whilst these cytokines were included in the majority of panels tested, they were only identified as independent predictors in two of the studies (49,50). Given the high level of co-variance between many cytokines, one explanation may be that individual cytokines negate each other in multi-variate analysis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of multiple cytokine analysis in colorectal cancer: a systematic review

Gunawardene

Dennett

Larsen

2018

J. Gastrointest. Oncol

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The link between inflammation and outcome has been established in colorectal cancer through experimental evidence demonstrating an influential role of pro-inflammatory cytokines on tumour growth and progression. Furthermore, prognostic scores based on overall markers of systemic inflammation such as C-reactive protein and neutrophil count have been validated. Over recent years, an increasing number of inflammatory cytokines have been identified as prognostic predictors in colorectal cancer and the aim of this review was to evaluate the literature on the prognostic value of multiple cytokine measurement. The English language literature published since the year 2000 was searched using terms including, 'colorectal cancer', 'cytokines' and 'prognosis' through Medline, Embase and Scopus databases. Reports were screened by two independent reviewers and studies evaluating fewer than three cytokines were excluded. Quality assessments were performed in six domains before data extraction was undertaken in duplicate. Seven studies were found to evaluate multiple cytokines after 570 records were screened. The quality of these studies ranged from poor to moderate and were heterogeneous in terms of the patient population and the number and selection of cytokines tested. Four studies combined multiple cytokine levels into a single score and found them to be predictive of prognosis whereas the association between individual cytokines and outcome was not demonstrated consistently. The combination of multiple cytokine markers into a single prognostic score shows promise in colorectal cancer and further research is required to establish and validate such a score.

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Prognostic and clinicopathological significance of serum interleukin-6 expression in colorectal cancer: a systematic review and meta-analysis

Cited by 18 publications

References 47 publications

Inhibition of MK2 suppresses IL‐1β, IL‐6, and TNF‐α‐dependent colorectal cancer growth

Inhibition of MK2 suppresses IL‐1β, IL‐6, and TNF‐α‐dependent colorectal cancer growth

Elevated IL‑6/IL‑1Ra ratio as a prognostic biomarker of poor chemotherapy efficacy in Chinese patients with metastatic NSCLC, validated in a Caucasian patient cohort

Prognostic value of multiple cytokine analysis in colorectal cancer: a systematic review

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