CD157 enhances malignant pleural mesothelioma aggressiveness and predicts poor clinical outcome

Our plain-English summary of CD157 enhances malignant pleural mesothelioma aggressiveness and predicts poor clinical outcome, by E. Ortolan, A. Giacomino, F. Martinetto, et al (Oncotarget, 2014).

The study

• Authors: E. Ortolan, A. Giacomino, F. Martinetto, S. Morone, N. Lo Buono, E. Ferrero, G. Scagliotti, S. Novello, S. Orecchia, E. Ruffini, I. Rapa, L. Righi, M. Volante, A. Funaro
• Journal: Oncotarget
• Published: 2014;5(15):6191-205
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma is a deadly tumor whose diagnosis and treatment remain very challenging. There is an urgent need to advance our understanding of mesothelioma biology and to identify new molecular markers for improving management of patients. CD157 is a membrane glycoprotein linked to ovarian cancer progression and mesenchymal differentiation. The common embryonic origin of ovarian epithelial cells and mesothelial cells and the evident similarities between ovarian and mesothelial cancer prompted us to investigate the biological role and clinical significance of CD157 in malignant pleural mesothelioma (MPM). CD157 mRNA and protein were detected in four of nine MPM cell lines of diverse histotype and in 85.2% of MPM surgical tissue samples (32/37 epithelioid; 37/44 biphasic). CD157 expression correlated with clinical aggressiveness in biphasic MPM. Indeed, high CD157 was a negative prognostic factor and an independent predictor of poor survival for patients with biphasic MPM by multivariate survival analysis (HR = 2.433, 95% CI 1.120-5.284; p = 0.025). In mesothelioma cell lines, CD157 gain (in CD157-negative cells) or knockdown (in CD157-positive cells) affected cell growth, migration, invasion and tumorigenicity, most notably in biphasic MPM cell lines. In these cells, CD157 expression was associated with increased activation of the mTOR signaling pathway, resulting in decreased platinum sensitivity. Moreover, a trend towards reduced survival was observed in patients with biphasic MPM receiving postoperative platinum-based chemotherapy. These findings indicate that CD157 is implicated in multiple aspects of MPM progression and suggest that CD157 expression could be used to stratify patients into different prognostic groups or to select patients that might benefit from particular chemotherapeutic approach.

In plain English

This laboratory and clinical study from Torino, Italy, examined the protein CD157 in malignant pleural mesothelioma. The authors tested nine mesothelioma cell lines and retrospectively stained tumors from 81 patients operated on from 1998 to 2005 (37 epithelioid, 44 biphasic), plus 20 sarcomatoid biopsies. CD157 appeared in 85.2% of surgical specimens and 9 of 20 sarcomatoid biopsies. Across all 81 patients, CD157 was not associated with asbestos history or outcome; in epithelioid tumors it did not correlate with survival. In biphasic patients, median survival was 13.067 months (95% CI 4.771 to 21.362) for the 23 with high CD157 (H-score above 50) versus 20.433 months (95% CI 16.546 to 24.321) for the 21 with an H-score of 50 or less (p = 0.037). High CD157 remained an independent survival predictor in multivariate analysis. In biphasic cell lines, changing CD157 levels altered growth, migration, invasion and resistance to cisplatin and carboplatin; rapamycin restored drug sensitivity. In biphasic patients given platinum chemotherapy, shorter survival with high CD157 was not statistically significant. The authors concluded CD157 could help sort biphasic patients into prognostic groups.

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 study of mesothelioma cell lines combined with a retrospective analysis of patient tumor specimens and survival
• Who was studied: Nine human malignant pleural mesothelioma cell lines. Tumor specimens from 81 consecutive patients operated on for malignant pleural mesothelioma between 1998 and 2005 at San Giovanni Hospital, Torino, Italy (37 epithelioid, 44 biphasic). Also 20 consecutive thoracoscopic biopsies of sarcomatoid mesothelioma diagnosed between 2004 and 2010 at San Luigi Hospital, Orbassano, Italy.
• Exposure: The factor studied was the level of the protein CD157 in tumors, not asbestos exposure. Occupational exposure to asbestos was documented in 41 of the 81 surgical patients. No fiber types are given.
• Main results:
  • CD157 was detected in 85.2% of the 81 surgical specimens: 86.5% of epithelioid and 84% of biphasic tumors.
  • In the cell lines, CD157 was detected in two of five epithelioid lines and one of three biphasic lines. The one sarcomatoid line was negative.
  • CD157 was present in 9 of 20 (45%) sarcomatoid biopsies.
  • Across all 81 surgical specimens, CD157 level was not associated with sex, age, histology, asbestos history, disease stage or patient outcome.
  • In epithelioid tumors, CD157 level did not correlate with survival.
  • In the 44 biphasic patients, median survival was 13.067 months (95% CI 4.771 to 21.362) with a CD157 H-score above 50, and 20.433 months (95% CI 16.546 to 24.321) with an H-score of 50 or less (log-rank p = 0.037).
  • In Table 1B (biphasic patients), 21 patients had a CD157 H-score of 50 or less and 23 had an H-score above 50.
  • In biphasic patients, the multivariable Cox model found CD157 H-score to be an independent predictor of survival. Table 1B reports a hazard ratio of 2.433 (95% CI 1.120 to 5.284; p = 0.025).
  • In biphasic patients, CD157 located in the cell membrane was associated with the worst prognosis (HR 2.031, 95% CI 1.022 to 4.038).
  • Adding or removing CD157 changed cell growth in biphasic cell lines but not in epithelioid lines.
  • Adding CD157 increased invasiveness in one biphasic line (MSTO) and one epithelioid line (REN).
  • Biphasic cell lines expressing CD157 showed higher activation of the mTOR signaling pathway.
  • Biphasic cell lines expressing CD157 were more resistant to cisplatin and carboplatin. Pretreatment with rapamycin, an mTOR inhibitor, brought back sensitivity to both drugs.
  • Among the 22 of 44 biphasic patients given postoperative platinum-based chemotherapy, those with a CD157 H-score above 50 showed a trend toward shorter survival, but the difference was not statistically significant (p = 0.062).
• The authors' conclusion: The authors concluded that CD157 is involved in several aspects of malignant pleural mesothelioma progression and may be useful as a marker for sorting patients with biphasic mesothelioma into different prognostic groups.
• Limitations the authors state:
  • Because the cohort came from surgical patients, it did not reflect the usual proportion of epithelioid tumors.
  • No surgical specimens from sarcomatoid patients were available, because surgery was not an option for them.
  • The authors stated that further studies are needed before drawing definitive conclusions from the clinical chemotherapy data.

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, Malignant Mesothelioma, Mesothelioma, Glycoprotein, Ovarian Cancer, Mesothelial Cells, Epithelioid, Biphasic Mesothelioma.

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• Mesothelioma cells breaking bad: loss of integrin α7 promotes cell motility and poor clinical outcomes in patients — D.J. Burkin, T.M. Fontelonga (2015)
• Epigenetic down-regulation of integrin α7 increases migratory potential and confers poor prognosis in malignant pleural mesothelioma — V. Laszlo, M.A. Hoda, et al. (2015)
• Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma — S. Inaguma, J. Lasota, et al. (2018)
• Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China — Z. Jiang, W. Shen, et al. (2020)
• Retrospective response analysis of BAP1 expression to predict the clinical activity of systemic cytotoxic chemotherapy in mesothelioma — N. Kumar, D. Alrifai, et al. (2019)

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