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๐Ÿง‘๐Ÿผโ€๐Ÿ’ป Research - September 30, 2024

Machine learning and biological validation identify sphingolipids as potential mediators of paclitaxel-induced neuropathy in cancer patients.

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โšก Quick Summary

A recent study utilized machine learning and lipidomics to identify specific sphingolipids, particularly sphinganine-1-phosphate (SA1P), as potential mediators of paclitaxel-induced neuropathy in cancer patients. The findings suggest that targeting SA1P could help mitigate one of the major side effects of paclitaxel therapy.

๐Ÿ” Key Details

  • ๐Ÿ“Š Participants: 31 breast cancer patients
  • ๐Ÿงช Methodology: High-resolution mass spectrometry lipidomics
  • โš™๏ธ Analysis Techniques: Supervised statistical and machine-learning methods
  • ๐Ÿ† Key Lipid Identified: Sphinganine-1-phosphate (SA1P)
  • ๐Ÿ“ˆ Accuracy: Median balanced accuracy of up to 90% in identifying blood samples pre- and post-therapy

๐Ÿ”‘ Key Takeaways

  • ๐Ÿ’ก Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of anticancer drugs like paclitaxel.
  • ๐Ÿ” Lipid analysis revealed 27 lipids that could differentiate between patients with and without neuropathy.
  • โšก SA1P was linked to calcium transients in sensory neurons, indicating its role in neuropathic pain.
  • ๐Ÿฉธ Blood concentration levels of SA1P varied significantly between neuropathy-affected and unaffected patients.
  • ๐Ÿ”ฌ Potential Target: SA1P may serve as a drug target for co-therapy with paclitaxel.
  • ๐ŸŒ Study Funded by: Deutsche Forschungsgemeinschaft and Fraunhofer Foundation.
  • ๐Ÿ“… Published in: Elife, 2024.

๐Ÿ“š Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition that affects many cancer patients undergoing treatment. It can lead to significant discomfort and may limit the effectiveness of chemotherapy regimens. Previous research has indicated that lipids might play a crucial role in the development of CIPN, prompting further investigation into specific lipid mediators associated with this condition.

๐Ÿ—’๏ธ Study

The study involved 31 breast cancer patients who underwent paclitaxel therapy. Researchers employed high-resolution mass spectrometry lipidomics to analyze blood samples collected before and after treatment. By applying various machine-learning algorithms, they aimed to identify lipid profiles that could predict the onset of neuropathy in these patients.

๐Ÿ“ˆ Results

The analysis identified 27 lipids that provided significant information for training machine learning models. Notably, the model achieved a median balanced accuracy of up to 90% in distinguishing between pre- and post-therapy blood samples. Among the identified lipids, sphinganine-1-phosphate (SA1P) emerged as a key player, showing distinct concentration differences in patients with neuropathy compared to those without.

๐ŸŒ Impact and Implications

The findings of this study could have profound implications for the management of CIPN in cancer patients. By identifying SA1P as a potential mediator of neuropathic pain, there is an opportunity to develop targeted therapies that could alleviate this debilitating side effect. This research not only enhances our understanding of the biological mechanisms underlying CIPN but also opens new avenues for therapeutic interventions that could improve patient quality of life during cancer treatment.

๐Ÿ”ฎ Conclusion

This study highlights the potential of machine learning and lipidomics in uncovering critical biological insights related to chemotherapy-induced side effects. The identification of sphinganine-1-phosphate as a significant mediator of paclitaxel-induced neuropathy presents a promising target for future therapeutic strategies. Continued research in this area is essential to enhance cancer care and improve patient outcomes.

๐Ÿ’ฌ Your comments

What are your thoughts on the role of lipids in chemotherapy-induced neuropathy? Weโ€™d love to hear your insights! ๐Ÿ’ฌ Share your comments below or connect with us on social media:

Machine learning and biological validation identify sphingolipids as potential mediators of paclitaxel-induced neuropathy in cancer patients.

Abstract

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious therapy-limiting side effect of commonly used anticancer drugs. Previous studies suggest that lipids may play a role in CIPN. Therefore, the present study aimed to identify the particular types of lipids that are regulated as a consequence of paclitaxel administration and may be associated with the occurrence of post-therapeutic neuropathy.
METHODS: High-resolution mass spectrometry lipidomics was applied to quantify d=255 different lipid mediators in the blood of n=31 patients drawn before and after paclitaxel therapy for breast cancer treatment. A variety of supervised statistical and machine-learning methods was applied to identify lipids that were regulated during paclitaxel therapy or differed among patients with and without post-therapeutic neuropathy.
RESULTS: Twenty-seven lipids were identified that carried relevant information to train machine learning algorithms to identify, in new cases, whether a blood sample was drawn before or after paclitaxel therapy with a median balanced accuracy of up to 90%. One of the top hits, sphinganine-1-phosphate (SA1P), was found to induce calcium transients in sensory neurons via the transient receptor potential vanilloid 1 (TRPV1) channel and sphingosine-1-phosphate receptors.SA1P also showed different blood concentrations between patients with and without neuropathy.
CONCLUSIONS: Present findings suggest a role for sphinganine-1-phosphate in paclitaxel-induced biological changes associated with neuropathic side effects. The identified SA1P, through its receptors, may provide a potential drug target for co-therapy with paclitaxel to reduce one of its major and therapy-limiting side effects.
FUNDING: This work was supported by the Deutsche Forschungsgemeinschaft (German Research Foundation, DFG, Grants SFB1039 A09 and Z01) and by the Fraunhofer Foundation Project: Neuropathic Pain as well as the Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD). This work was also supported by the Leistungszentrum Innovative Therapeutics (TheraNova) funded by the Fraunhofer Society and the Hessian Ministry of Science and Arts. Jรถrn Lรถtsch was supported by the Deutsche Forschungsgemeinschaft (DFG LO 612/16-1).

Author: [‘Lรถtsch J’, ‘Gasimli K’, ‘Malkusch S’, ‘Hahnefeld L’, ‘Angioni C’, ‘Schreiber Y’, ‘Trautmann S’, ‘Wedel S’, ‘Thomas D’, ‘Ferreiros Bouzas N’, ‘Brandts CH’, ‘Schnappauf B’, ‘Solbach C’, ‘Geisslinger G’, ‘Sisignano M’]

Journal: Elife

Citation: Lรถtsch J, et al. Machine learning and biological validation identify sphingolipids as potential mediators of paclitaxel-induced neuropathy in cancer patients. Machine learning and biological validation identify sphingolipids as potential mediators of paclitaxel-induced neuropathy in cancer patients. 2024; 13:(unknown pages). doi: 10.7554/eLife.91941

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