Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients

Our plain-English summary of Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients, by T. Kishimoto, N. Fujimoto, T. Ebara, et al (BMC Cancer, 2019).

The study

• Authors: T. Kishimoto, N. Fujimoto, T. Ebara, T. Omori, T. Oguri, A. Niimi, T. Yokoyama, M. Kato, I. Usami, M. Nishio, K. Yoshikawa, T. Tokuyama, M. Tamura, Y. Yokoyama, K. Tsuboi, Y. Matsuo, J. Xu, S. Takahashi, M. Abdelgied, W.T. Alexander, D.B. Alexander, H. Tsuda
• Journal: BMC Cancer
• Published: 2019;19(1):1204
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients.

Methods: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA.

Results: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM.

Conclusions: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.

In plain English

This Japanese study used a laboratory test (ELISA) to measure serum levels of the chemokine CCL2 in 50 patients with malignant pleural mesothelioma, 356 people possibly exposed to asbestos with no detectable asbestos-associated disease, and 41 healthy volunteers with no history of asbestos exposure. The mean level in the mesothelioma patients was 421.3 ± 295.1 pg/ml. This was significantly higher than the possibly exposed group (307.5 ± 117.7) and unexposed volunteers (275.2 ± 98.2). The rise depended on disease stage: means were 289.9 at stage 1, 281.0 at stage 2, 486.0 at stage 3 and 493.5 at stage 4. Mesothelioma levels stayed significantly higher than both other groups after adjusting for age and gender, and also after removing two patients with extraordinarily high levels. With both steps combined, significance held only against the possibly exposed group. The possibly exposed group tended to be higher than the unexposed volunteers, but the difference was not statistically significant. The authors lacked that group's hospital records to rule out other conditions raising CCL2. The authors concluded that CCL2 is elevated in mesothelioma patients and that the increase depends on stage.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cross-sectional comparison of serum CCL2 levels between mesothelioma patients and two groups without apparent disease
• Who was studied: 50 malignant pleural mesothelioma patients (5 women, 45 men; age 72.5 ± 8.6 years), diagnosed by biopsy and chest CT, with sarcomatoid, epithelioid and biphasic types. 356 healthy subjects possibly exposed to asbestos (33 women, 323 men; age 68.7 ± 8.3 years). 41 healthy unexposed volunteers (10 women, 31 men; age 56 ± 20.0 years). Samples came from hospitals and a university in Japan. Dates of collection were not given.
• Exposure: Possible past asbestos exposure, documented by Japanese Ministry of Health, Labour and Welfare certificates for compensation of medical care. Fiber types, jobs and doses were not reported for any group. The measured outcome was serum CCL2.
• Main results:
  • Mean serum CCL2 was 421.3 ± 295.1 pg/ml in all 50 mesothelioma patients. It was 307.5 ± 117.7 in the possibly exposed group and 275.2 ± 98.2 in the unexposed volunteers. The mesothelioma level differed from the unexposed group at p less than 0.01 and from the possibly exposed group at p less than 0.05 (Table 1).
  • By stage, mean serum CCL2 was 289.9 ± 115.4 pg/ml at stage 1 (12 patients), 281.0 ± 111.2 at stage 2 (5 patients), 486.0 ± 333.4 at stage 3 (14 patients) and 493.5 ± 346.7 at stage 4 (19 patients). Stages 3 and 4 differed from both healthy groups at p less than 0.001 and from stage 1 at p less than 0.01.
  • After adjusting for age and gender, the estimated mean for all mesothelioma patients was 411.8 pg/ml (95% CI 370.9 to 452.6). For the possibly exposed group it was 305.6 (95% CI 290.4 to 320.8), and for the unexposed volunteers 303.5 (95% CI 256.0 to 351.1). The mesothelioma level remained significantly higher than both.
  • Two mesothelioma patients had extraordinarily high levels. After they were removed, the unadjusted mean for all mesothelioma patients was 368.5 ± 138.1 pg/ml, which differed from both groups without apparent disease at p less than 0.01. With age and gender adjustment as well, the estimated mean was 356.0 pg/ml (95% CI 322.8 to 389.2). This differed significantly only from the possibly exposed group (p less than 0.05). The authors reported that the dependence on stage was still apparent.
  • The possibly exposed group tended to have higher serum CCL2 than the unexposed volunteers, but the difference was not statistically significant. The authors noted that the possibly exposed group was older on average.
• The authors' conclusion: The authors concluded that CCL2 levels are elevated in mesothelioma patients and that the increase depends on disease stage. In their view, this is consistent with the CCL2/CCR2 axis and myeloid-derived cells playing a role in mesothelioma and its progression.
• Limitations the authors state:
  • Hospital records were not available for subjects without mesothelioma. It is therefore unknown whether some had health conditions or treatments that raised their serum CCL2.
  • Serum CCL2 rises with age, and the groups differed in age and gender. The authors re-analyzed the data adjusting for these factors.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pleural Cavity, Inflammation, Macrophage, Etiology, Pleural Effusion, Mesothelioma, Disease Progression.

Related studies

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• Elevated Circulating Activin A Levels in Patients With Malignant Pleural Mesothelioma Are Related to Cancer Cachexia and Reduced Response to Platinum-based Chemotherapy — J. Paajanen, I. Ilonen, et al. (2020)
• Elevated Serum Megakaryocyte Potentiating Factor as a Predictor of Poor Survival in Patients with Mesothelioma and Primary Lung Cancer — Y. Yu, B.M. Ryan, et al. (2018)
• Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma: A meta-analysis — Y. Zhuo, L. Lin, et al. (2016)
• The Correlation of Serum Mesothelin Level With Pleural Thickness in Malignant Pleural Mesothelioma Makes it a Valuable Tool for Monitoring Tumor Progression — V. Fontana, A. Vigani, et al. (2019)

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