Serum Levels of N- and C-ERC/Mesothelin and Clinicopathological Factors in Mesothelioma Patients and Those without Mesothelioma

Our plain-English summary of Serum Levels of N- and C-ERC/Mesothelin and Clinicopathological Factors in Mesothelioma Patients and Those without Mesothelioma, by A.I. Koyanagi, K. Kajino, S. Nojiri, et al (Juntendō Iji Zasshi = Juntendo Medical Journal, 2023).

The study

• Authors: A.I. Koyanagi, K. Kajino, S. Nojiri, M. Abe, T. Kobayashi, Y. Sugitani, L. Yue, N. Ohtsuji, A. Arakawa, T. Sato, K. Takahashi, K. Suzuki, A. Orimo, T. Yao, O. Hino
• Journal: Juntendō Iji Zasshi = Juntendo Medical Journal
• Published: 2023;69(2):124-136
• Read it: PubMed · Publisher · Free full text

Abstract

Objectives: ERC/mesothelin is a glycosylphosphatidylinositol (GPI)-anchor protein expressed in mesothelioma. A precursor protein is cleaved by proteases and an N-terminal fragment (N-ERC) is extracellularly secreted. A remaining C-terminal fragment (C-ERC) is tethered on cellular membranes by the GPI-anchor, but C-ERC is also released after cleavage by proteases. We and other groups reported that serum N-/C-ERC levels are associated with stages of mesothelioma and suggested the possibility of their usefulness as diagnostic markers. However, the N-ERC level is also influenced by renal functions that are not directly associated with conditions of mesothelioma. It is not known whether other clinical factors influence serum N-/C-ERC values. Furthermore, their relationship to the amount of ERC/Mesothelin in mesothelioma is not yet validated. The objective of this study is to clarify the relationship of serum N-/C-ERC levels and the status of mesothelioma and several clinical factors.

Materials And Methods: We analyzed relations of serum N-/C-ERC levels and ages, gender and other clinical factors in 522 patients without mesothelioma and examined their relation to the amount of ERC/Mesothelin in mesothelioma tissues in 13 mesothelioma cases.

Results: Serum N-ERC levels were influenced by renal functions. On the contrary, those of C-ERC were not influenced by any clinical factors examined in this study and were significantly correlated with the amount of ERC/Mesothelin in mesothelioma.

Conclusion: Although both markers are good indicators of treatment-responses in individual patients with mesothelioma, only C-ERC reflected the amount of ERC/Mesothelin in mesothelioma among multiple patients, possibly because N-ERC was influenced by renal functions.

© 2023 The Juntendo Medical Society.

In plain English

This study, from the Asbestos/mesothelioma clinic at Juntendo University in Tokyo, measured two blood fragments of the protein ERC/mesothelin, N-ERC and C-ERC. It included 42 mesothelioma patients and 522 outpatients without clinical evidence of mesothelioma, seen between 2005 and 2019. The article did not report an assessment of asbestos exposure. Average levels of both markers were higher in 42 mesothelioma patients than in 518 of the outpatients without mesothelioma (N-ERC 19.0 versus 5.4 ng/mL; C-ERC 15.7 versus 3.8 ng/mL; p less than 0.05). In 13 mesothelioma patients with tumor images, serum C-ERC was associated with the estimated amount of ERC-positive tumor (p = 0.0005), but N-ERC was not. Among patients without mesothelioma, N-ERC rose with serum creatinine, a kidney-function marker, but C-ERC did not. Other factors examined, including age, sex, inflammation and diabetes, showed no correlation with either marker. In two patients followed during chemotherapy, both markers tracked tumor burden. The authors concluded that the values must be interpreted carefully across different patients, but both markers remain useful for monitoring individual patients. They noted that the tissue comparison involved only 13 cases.

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: Biomarker study comparing serum N-ERC and C-ERC levels between patients with and without mesothelioma, with tissue staining and tumor-volume analysis in a subset; chemotherapy course data obtained retrospectively
• Who was studied: 42 mesothelioma patients (33 male, 9 female; 34 epithelioid, 3 biphasic, 3 sarcomatoid, 2 desmoplastic) and 522 outpatients (421 male, 101 female) with no clinical evidence of mesothelioma, from the Asbestos/mesothelioma clinic at Juntendo University, Tokyo, Japan, 2005 to 2019; tumor-volume analysis in 13 mesothelioma patients (11 epithelioid, 2 biphasic)
• Exposure: The article did not report an assessment of asbestos exposure for study participants, and no fiber types are named. The clinic was set up to screen asbestos-exposed laborers and their family members. The study's measured variables were serum N-ERC and C-ERC levels and how they related to tumor ERC content and to clinical factors.
• Main results:
  • Serum N-ERC was 19.0 plus or minus 24.7 in 42 mesothelioma patients versus 5.4 plus or minus 9.5 in 518 patients without mesothelioma (p less than 0.05). Serum C-ERC was 15.7 plus or minus 36.2 versus 3.8 plus or minus 8.4 (p less than 0.05). The tables give serum levels in ng/mL.
  • N-ERC and C-ERC levels were positively correlated with each other: correlation coefficient 0.71 in mesothelioma patients and 0.54 in patients without mesothelioma
  • In 13 mesothelioma patients, serum C-ERC correlated positively with ERC-positive tumor volume, but serum N-ERC did not
  • In the 13 patients, the p-value for the relationship with ERC-positive volume was 0.0005 for C-ERC and 0.69 for N-ERC. For tumor volume alone, the p-values were 0.28 for C-ERC and 0.11 for N-ERC (not significant).
  • In patients without mesothelioma (504 in the creatinine analysis), serum creatinine correlated positively with N-ERC but not with C-ERC
  • In patients without mesothelioma, none of the other clinical parameters examined (age, gender, CRP, albumin, hemoglobin, platelets, ALT, HbA1c) correlated with either marker
  • Among the 522 patients without mesothelioma, the text reports 43 C-higher patients (C-ERC more than twice N-ERC) and 184 N-higher patients (N-ERC more than twice C-ERC)
  • The N-higher group (142 male, 42 female) had a larger share of women than the C-higher group (37 male, 3 female), p less than 0.05. No other clinical factor differed between the groups.
  • In 2 mesothelioma patients followed during chemotherapy, both N-ERC and C-ERC reflected tumor burden
• The authors' conclusion: The authors concluded that serum C- and N-ERC values must be interpreted with caution as mesothelioma markers when comparing different patients, partly because N-ERC is influenced by renal function. They concluded that both markers are still valuable for monitoring mesothelioma in individual patients.
• Limitations the authors state:
  • The authors suggested that the small number of tissue cases (13) may explain why no significant relationship was seen between serum C-ERC and tumor volume
  • The authors stated that the reason for the sex difference between the N-higher and C-higher groups is unknown

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Mesothelioma.

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