Hedgehog Signaling in Mesothelioma: 2019 Status

Our plain-English summary of Hedgehog Signaling in Mesothelioma: 2019 Status, by E. Felley-Bosco (Frontiers in Genetics, 2019).

The study

• Author: E. Felley-Bosco
• Journal: Frontiers in Genetics
• Published: 2019;10:1121
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

In plain English

This was a short opinion article by a single author, not a new study of patients or workers. The author discussed whether hedgehog signaling, a cell-signaling pathway, could matter for treating malignant pleural mesothelioma. The article describes this cancer as mostly associated with exposure to asbestos. The author's own analysis of public tumor data (TCGA) found that few mesothelioma patients had PTCH1 truncation mutations or SUFU deep deletions. It also found a statistically significant co-occurrence of alterations in several parts of the pathway. The article summarized earlier studies, including some by the author's group. In two patient groups, high GLI-1 levels were linked to worse overall survival. The pathway was activated as mesothelioma developed in mice exposed to asbestos. In one earlier trial, Smo-blocking drugs were given to only three unselected mesothelioma patients, and none responded. The author noted that part of the hedgehog signal might come from surrounding tissue (stroma) rather than tumor cells. The author concluded that hedgehog signaling likely promotes tumor growth in some malignant pleural mesothelioma and called for coordinated further research.

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: Opinion article (short commentary reviewing published studies, plus the author's look at public TCGA tumor data)
• Who was studied: No new patients were studied. The article discusses published studies and public TCGA mesothelioma tumor data; the number of TCGA samples is not stated.
• Exposure: Not an exposure study. The subject is hedgehog signaling in malignant pleural mesothelioma. Asbestos is mentioned only as background, citing a review, and no fiber types are named.
• Main results:
  • The author's analysis of TCGA mesothelioma data: few patients had PTCH1 truncation mutations or SUFU deep deletions, and alterations in several hedgehog pathway components showed statistically significant co-occurrence.
  • In the TCGA data, pathway alterations did not strictly correlate with ligand expression, and DHH was the ligand with the highest differential level.
  • Cited from earlier work (Shi et al., 2012, and a TCGA analysis), not new data: high GLI-1 expression was significantly associated with worse overall survival in two independent patient cohorts.
  • Cited from the author's group's earlier study (Rehrauer et al., 2018): hedgehog signaling was activated during mesothelioma development in mice exposed to asbestos.
  • Cited from an earlier trial (LoRusso et al., 2011): Smo inhibitors were tested in only three unselected mesothelioma patients, and no response was observed.
• The authors' conclusion: The author concluded that hedgehog signaling likely acts as a pro-tumor signal in some malignant pleural mesothelioma. The author called on the mesothelioma research community to coordinate further investigation.
• Limitations the authors state:
  • Part of the hedgehog activation signature may reflect activity of surrounding stromal tissue rather than tumor cells.
  • It is not known whether the five-gene hedgehog signature used to select medulloblastoma patients would apply to mesothelioma.
  • Prognostic findings differed between the TCGA data and two other datasets, and the reasons are unclear.

Topics

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

Related studies

• Hedgehog Signaling in Malignant Pleural Mesothelioma — E. Felley-Bosco, I. Opitz, et al. (2015)
• Mutational analysis of hedgehog signaling pathway genes in human malignant mesothelioma — C.B. Lim, C.M. Prêle, et al. (2013)
• CK2α, over-expressed in human malignant pleural mesothelioma, regulates the Hedgehog signaling pathway in mesothelioma cells — S. Zhang, Y.L. Yang, et al. (2014)
• Inhibition of hedgehog signaling reduces the side population in human malignant mesothelioma cell lines — H.A. Kim, M.C. Kim, et al. (2015)
• HDACi inhibits liposarcoma via targeting of the MDM2-p53 signaling axis and PTEN, irrespective of p53 mutational status — W.B. Ou, J. Zhu, et al. (2015)
• Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma — M. Meerang, K. Bérard, et al. (2016)

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