Novel circulating tumor cell-detection chip combining conventional podoplanin and EGFR antibodies for all histological malignant pleural mesothelioma

Our plain-English summary of Novel circulating tumor cell-detection chip combining conventional podoplanin and EGFR antibodies for all histological malignant pleural mesothelioma, by M. Kanayama, R. Oyama, M. Mori, et al (Oncology Letters, 2021).

The study

• Authors: M. Kanayama, R. Oyama, M. Mori, A. Taira, S. Shinohara, T. Kuwata, M. Takenaka, K. Yoneda, K. Kuroda, T. Ohnaga, Y. Kato, F. Tanaka
• Journal: Oncology Letters
• Published: 2021;22(1):522
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In our previous study, a microfluidic system was developed based on podoplanin detection for capturing circulating tumor cells (CTCs), derived from malignant pleural mesothelioma (MPM). However, non-epithelioid MPM shows low podoplanin protein expression compared with that in epithelioid MPM; thus, some CTC populations may be missed. To overcome this limitation, a new CTC-detection chip was developed by combining the conventional podoplanin antibody (clone: NZ-1.2) with an epidermal growth factor receptor (EGFR)-targeted antibody (cetuximab). The cell-capture efficiency of the Cocktail-chip reached 100% in all the histological MPM cell lines. The median CTC-counts from 19 patients with MPM (epithelioid/non-epithelioid: 10/9) with the NZ-1.2- and Cocktail-chips were 1 and 3 (P=0.311) in 1 ml peripheral blood, 1.5 and 2 (P=0.332) in epithelioid MPM, and 1 and 3 (P=0.106) in non-epithelioid MPM, respectively. Overall, the Cocktail-chip showed an improved ability to detect more CTCs in patients with non-epithelioid MPM compared with that in the conventional NZ-1.2-chip, showing non-significant, but higher CTC detection. Furthermore, CTC-counts, determined using the Cocktail-chip were significantly correlated with the clinical stage of non-epithelioid MPM. In epithelioid MPM, the Cocktail-chip achieved a CTC-detection efficiency equivalent to that in the conventional NZ-1.2-chip. The Cocktail-chip enabled sensitive CTC detection of all histological MPM, including the non-epithelioid subtype, which may provide a foundation for the diagnosis, treatment, and prognosis of MPM progression.

Copyright: © Kanayama et al.

In plain English

This Japanese study tested a new blood-test device for malignant pleural mesothelioma (MPM). It did not examine asbestos exposure. The chip catches circulating tumor cells shed into the blood. An earlier chip used a podoplanin antibody (NZ-1.2); podoplanin is weaker in non-epithelioid MPM. The new Cocktail-chip added cetuximab, an antibody to the protein EGFR. In five MPM cell lines, the Cocktail-chip captured 100% of cells. Blood from 19 male patients was run on both chips. Median tumor-cell counts per 1 ml of blood, older chip versus Cocktail-chip, were 1 and 3 overall (P=0.311) and 1 and 3 in the 9 non-epithelioid patients (P=0.106), neither statistically significant. No cells were found in five healthy volunteers. In non-epithelioid patients, Cocktail-chip counts were significantly correlated with disease stage. Survival did not differ significantly by tumor-cell detection. The authors concluded it could detect tumor cells in all MPM types, matching the older chip in epithelioid MPM and finding more, though not significantly more, cells in non-epithelioid MPM. They noted the small group, one blood test per patient, and that captured cells were not confirmed as MPM cells.

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: Laboratory experiment with mesothelioma cell lines, plus a small clinical comparison of two cell-capture chips run on the same blood samples from patients with MPM
• Who was studied: 5 human MPM cell lines (3 epithelioid, 1 biphasic, 1 sarcomatoid). Blood from 19 patients with MPM (10 epithelioid, 9 non-epithelioid), collected January 2018 to August 2020 at diagnosis or before treatment. All 19 were male, mean age 69.0 (range 55-78). Blood from 5 healthy volunteers recruited from laboratory staff. The study was approved by the Ethics Committee of the University of Occupational and Environmental Health, Japan.
• Exposure: No asbestos or other exposure was studied. The study compared three detection chips: the earlier NZ-1.2-chip (anti-podoplanin antibody), a Cetuximab-chip (anti-EGFR), and the Cocktail-chip combining both antibodies.
• Main results:
  • In the laboratory cell lines, the Cocktail-chip captured 100% of cells in all MPM cell lines.
  • The Cetuximab-only chip had high capture in most cell lines, but only 40% capture in the epithelioid ACC-MESO-4 cell line.
  • In the 19 patients, both chips detected circulating tumor cells in 73.7% (14/19). In epithelioid MPM, the NZ-1.2-chip detected them in 90% (9/10) and the Cocktail-chip in 70% (7/10). In non-epithelioid MPM, the rates were 55.6% (5/9) and 77.7% (7/9).
  • Median counts per 1 ml of blood, NZ-1.2-chip versus Cocktail-chip, were as follows. Overall: 1 (range 0-9) and 3 (range 0-12), P=0.311. Epithelioid MPM: 1.5 (range 0-9) and 2 (range 0-12), P=0.332. Non-epithelioid MPM: 1 (range 0-4) and 3 (range 0-9), P=0.106. The authors reported no significant difference between the two chips.
  • In epithelioid MPM, the Cocktail-chip's detection efficiency was equivalent to that of the NZ-1.2-chip.
  • No cells were detected in the five healthy subjects.
  • With the Cocktail-chip, the correlation between counts and clinical stage was 0.763 (P=0.017) in non-epithelioid MPM and 0.108 (P=0.766) in epithelioid MPM. Across all patients, the correlation was 0.413 (P=0.079) with the Cocktail-chip and 0.194 (P=0.425) with the NZ-1.2-chip.
  • Survival did not differ significantly by whether tumor cells were detected, with either chip. Patients with tumor cells detected had poorer prognosis (P=0.274 for the NZ-1.2-chip and P=0.114 for the Cocktail-chip).
  • In patients' tumor tissue, podoplanin staining was negative or weak in 3 of 5 sarcomatoid cases, while no case was EGFR-negative.
• The authors' conclusion: The authors concluded that the Cocktail-chip was more effective at capturing circulating tumor cells from all histological types of MPM, including the non-epithelioid subtype. Their own results showed detection equivalent to the older chip in epithelioid MPM, and higher but not statistically significant counts in non-epithelioid MPM. They said further studies may reveal the chip's clinical value.
• Limitations the authors state:
  • Only 19 patients were included, which the authors call too small for a definitive conclusion on the Cocktail-chip's efficiency.
  • Tumor cells were detected and counted only once per patient.
  • There may have been experimental variability, because 1 ml of blood was used per chip and the protocol was not fully automated.
  • The study did not confirm that the captured cells were true MPM cells.
  • The survival analysis was insufficient because of the small number of cases and short observation in some cases.

Topics

Medical terms in this study, explained in our Lexicon: Podoplanin (D2-40), EGFR, Pleural Mesothelioma, Non-epithelioid, Epithelioid, Cetuximab (Erbitux), Prognosis.

Related studies

• Detection of Circulating Tumor Cells (CTCs) in Malignant Pleural Mesothelioma (MPM) with the "Universal" CTC-Chip and An Anti-Podoplanin Antibody NZ-1.2 — T. Kuwata, K. Yoneda, et al. (2020)
• Detection of circulating tumor cells with a novel microfluidic system in malignant pleural mesothelioma — K. Yoneda, T. Kuwata, et al. (2019)
• Establishing a Highly Accurate Circulating Tumor Cell Image Recognition System for Human Lung Cancer by Pre-Training on Lung Cancer Cell Lines — H. Matsumiya, K. Terabayashi, et al. (2025)
• EpCAM-independent capture of circulating tumor cells with a 'universal CTC-chip' — Y. Chikaishi, K. Yoneda, et al. (2017)
• Capture of mesothelioma cells with 'universal' CTC-chip — K. Yoneda, Y. Chikaishi, et al. (2018)
• Droplet digital PCR as a novel system for the detection of microRNA‑34b/c methylation in circulating DNA in malignant pleural mesothelioma — H. Sato, J. Soh, et al. (2019)

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