Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study

Our plain-English summary of Chemokine (C-C motif) ligand 3 detection in the serum of persons exposed to asbestos: A patient-based study, by J. Xu, D.B. Alexander, M. Iigo, et al (Cancer Science, 2015).

The study

• Authors: J. Xu, D.B. Alexander, M. Iigo, H. Hamano, S. Takahashi, T. Yokoyama, M. Kato, I. Usami, T. Tokuyama, M. Tsutsumi, M. Tamura, T. Oguri, A. Niimi, Y. Hayashi, Y. Yokoyama, K. Tonegawa, K. Fukamachi, M. Futakuchi, Y. Sakai, M. Suzui, M. Kamijima, N. Hisanaga, T. Omori, D. Nakae, A. Hirose, J. Kanno, H. Tsuda
• Journal: Cancer Science
• Published: 2015;106(7):825-32
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Exposure to asbestos results in serious risk of developing lung and mesothelial diseases. Currently, there are no biomarkers that can be used to diagnose asbestos exposure. The purpose of the present study was to determine whether the levels or detection rate of chemokine (C-C motif) ligand 3 (CCL3) in the serum are elevated in persons exposed to asbestos. The primary study group consisted of 76 healthy subjects not exposed to asbestos and 172 healthy subjects possibly exposed to asbestos. The secondary study group consisted of 535 subjects possibly exposed to asbestos and diagnosed with pleural plaque (412), benign hydrothorax (10), asbestosis (86), lung cancer (17), and malignant mesothelioma (10). All study subjects who were possibly exposed to asbestos had a certificate of asbestos exposure issued by the Japanese Ministry of Health, Labour and Welfare. For the primary study group, levels of serum CCL3 did not differ between the two groups. However, the detection rate of CCL3 in the serum of healthy subjects possibly exposed to asbestos (30.2%) was significantly higher (P < 0.001) than for the control group (6.6%). The pleural plaque, benign hydrothorax, asbestosis, and lung cancer groups had serum CCL3 levels and detection rates similar to that of healthy subjects possibly exposed to asbestos. The CCL3 chemokine was detected in the serum of 9 of the 10 patients diagnosed with malignant mesothelioma. Three of the patients with malignant mesothelioma had exceptionally high CCL3 levels. Malignant mesothelioma cells from four biopsy cases and an autopsy case were positive for CCL3, possibly identifying the source of the CCL3 in the three malignant mesothelioma patients with exceptionally high serum CCL3 levels. In conclusion, a significantly higher percentage of healthy persons possibly exposed to asbestos had detectable levels of serum CCL3 compared to healthy unexposed control subjects.

© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

In plain English

This Japanese study tested whether a blood protein, CCL3, is raised in people possibly exposed to asbestos. It compared 76 healthy unexposed people with 172 healthy people without lung or pleural lesions who held government asbestos exposure certificates. Another 535 certified people with pleural plaque, asbestosis, benign hydrothorax, lung cancer or malignant mesothelioma were also tested. Among participants with detectable CCL3, levels did not differ between the two healthy groups. CCL3 was detectable in 52 of 172 possibly exposed healthy people (30.2%) and 5 of 76 unexposed people (6.6%), an odds ratio of 6.15 (95% confidence interval 2.56 to 18.3). Detection rates in the plaque, asbestosis, hydrothorax and lung cancer groups resembled the possibly exposed healthy group. CCL3 was detected in 9 of 10 mesothelioma patients, three with very high levels, and in tumor cells of all five specimens examined. The authors said a 30% detection rate limits CCL3 as an exposure marker. Because CCL3 also rises in other conditions, they suggested repeated detection over time as an additional exposure marker only for people without symptoms. One author has filed a patent application for CCL3.

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: Patient-based comparison of serum CCL3 (a blood test) between groups, plus tissue staining of mesothelioma specimens
• Who was studied: 76 healthy unexposed controls (university staff and residents or patients at a Nagoya welfare center hospital) and 707 people possibly exposed to asbestos, seen at three Japanese hospitals from 2008 to 2012. The exposed people were 172 with no detectable lesions, 412 with pleural plaque (including 12 with pneumoconiosis), 86 with asbestosis, 10 with benign hydrothorax, 17 with lung cancer and 10 with malignant mesothelioma.
• Exposure: Possible asbestos exposure, defined by holding a certificate of asbestos exposure from the Japanese Ministry of Health, Labour and Welfare. Residents near asbestos factories with no asbestos-related job were included. Fiber types were not specified.
• Main results:
  • CCL3 was detectable in 52 of 172 healthy people possibly exposed to asbestos (30.2%) and in 5 of 76 unexposed controls (6.6%)
  • The odds ratio for CCL3 detection in the possibly exposed healthy group compared with controls was 6.15 (95% confidence interval 2.56 to 18.3), P less than 0.001
  • Among people with detectable CCL3, levels did not differ between healthy controls and healthy people possibly exposed to asbestos
  • In the primary study group, age and cigarette consumption were significantly associated with CCL3 levels. Age, gender, smoking, length of exposure and time since last exposure were not significantly associated with whether CCL3 was detected.
  • Detection rates in the disease groups were similar to the possibly exposed healthy group: asbestosis 34 of 86 (39.5%), benign hydrothorax 3 of 10 (30.0%), lung cancer 5 of 17 (29.4%). For pleural plaque, the text gives 139 of 412 (33.7%) but Table 5 gives 143 of 412 (34.7%).
  • CCL3 was detected in 9 of 10 malignant mesothelioma patients, significantly more often than in the other groups
  • Three mesothelioma patients had very high CCL3 levels of 611, 1007 and 2012 pg/mL. The higher levels in the mesothelioma group were entirely due to these three patients.
  • All 4 biopsy specimens and 1 autopsy specimen of malignant mesothelioma showed CCL3 in the tumor cells
• The authors' conclusion: The authors concluded that CCL3 is detectable in the blood of a significant percentage of asymptomatic people exposed to asbestos. They suggested that persistent detection over time could serve as an adjunct marker of asbestos exposure. Because CCL3 is not specific to asbestos, they considered this use appropriate only for asymptomatic individuals.
• Limitations the authors state:
  • A 30% detection rate suggests limited use of CCL3 as a biomarker for asbestos exposure
  • Asbestos fibers could not be confirmed in the healthy certified group, and the authors considered it unlikely that most of them actually had fibers in their lungs or pleura
  • CCL3 rises with infection and other insults, so multiple blood samples are needed. The test cannot distinguish asbestos exposure from other diseases that raise CCL3.
  • The small number of mesothelioma patients (10) precludes assessing CCL3 as a marker of malignant mesothelioma

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: Biomarker, Asbestos Exposure, Pleural Plaques, Lung Cancer, Mesothelioma, Biopsy, Autopsy.

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• Serum mesothelin for early detection of asbestos-induced cancer malignant mesothelioma — J. Creaney, N.J. Olsen, et al. (2010)
• Multi-walled carbon nanotubes translocate into the pleural cavity and induce visceral mesothelial proliferation in rats — J. Xu, M. Futakuchi, et al. (2012)
• Molecular tumor markers for asbestos-related mesothelioma: serum diagnostic markers — M. Maeda, O. Hino (2006)
• Detection of serum p53 protein in lung cancer patients — J.C. Luo, R. Zehab, et al. (1994)

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