Sphingolipids: A Promising Diagnostic Toolset for Breast Cancer Subtyping and Prognosis

Work done in the lab of Dr. Ujjaini Dasgupta at Amity University, Haryana

About author

Animesh is a highly qualified individual with a strong background in the field of biomedical science. He hails from Midnapore, West Bengal, and completed his undergraduate studies at the University of Delhi, earning a Bachelor’s degree in Biomedical Science. He then went on to earn a Master’s degree in Biophysics from the All India Institute of Medical Sciences in New Delhi. In 2016, he was accepted into the JGEEBILS program at the National Centre for Biological Sciences/Tata Institute of Fundamental Research and began his Ph.D. studies under the guidance of Professor Avinash Bajaj at the Regional Centre for Biotechnology in Faridabad and Dr. Ujjaini Dasgupta, Amity University Haryana. His research focuses on understanding the molecular mechanisms of tumor progression in various animal models and patient populations in response to chemotherapy. In addition to his work, Animesh has a passion for reading science fiction and non-fiction books, sketching scientific and non-scientific illustrations, and wildlife photography.

Interview

How would you explain your research outcomes to the non-scientific community?

In this study, we have investigated the role of sphingolipids in breast cancer progression. The study found that sphingolipids, which are a type of fat/lipid in the body, can be used for diagnosis and prediction of the severity of breast cancer. In this study, we used targeted liquid chromatography-mass spectrometry to perform a comparative analysis of sphingolipid profiles in breast cancer tissue samples from patients of luminal and triple-negative subtypes as well as the corresponding adjacent normal tissue from an Indian cohort.

Analysis of the level of sphingolipids in tumor and normal tissue samples led to the identification of a distinct five-sphingolipid signature that distinguished the two subtypes of breast cancer. We also found that these sphingolipid signatures can be used to predict the aggressive nature of cancer, specifically, whether it is a grade II or III tumor and if it has spread to nearby blood vessels causing lymph invasion. Therefore, the estimation of these sphingolipids from biopsy samples can help clinicians determine the best course of treatment for each patient. These findings may provide a foundation for the development of sphingolipid-based signatures that can serve as diagnostic and prognostic tools in breast cancer.

How do these findings contribute to your research area?

Sphingolipids have emerged as promising biomarkers in recent studies for the diagnosis and prognosis of several cancer types, including colorectal cancer, lung cancer, head and neck cancer, and squamous cell carcinoma. These lipids were shown to be deregulated in the breast tumour tissue of different subtypes, majorly from cohorts in western countries. Unlike the only study on an Indian cohort that has been reported so far (Bhadwal, Dahiya, et al. 2020) our study covers a larger sample size and systematically distinguishes the tumor from adjacent normal tissue and importantly the luminal from the TNBC subtype. Our work revealed a lipid signature that can distinguish between the two subtypes and discovered a correlation between altered lipid profiles for each subtype and clinicopathological parameters. These results promise to serve as a starting point for the establishment of sphingolipid-based signatures that can be used, particularly in the Indian population, as diagnostic and prognostic tools.

“Our work revealed a lipid signature that can distinguish between the two subtypes and discovered a correlation between altered lipid profiles for each subtype and clinicopathological parameters. “

What was the exciting moment during your research?

At the initial stages, our preliminary analysis of the sphingolipid levels in a subset of breast cancer patients did not yield any significant findings. However, upon integrating additional patient information, such as age, menopausal status, and the presence of lymph invasion, a clear pattern began to emerge in a larger cohort of patients. This pattern was dependent on various clinicopathological factors related to the patients upon diagnosis. Careful analysis and interpretation of this pattern identified differences in levels of certain sphingolipid species that could distinguish between different subtypes of breast cancer and levels of tumor severity.

What do you hope to do next?

The research presented in this study has the potential to pave the way for the development of sphingolipid-based signatures as diagnostic and prognostic tools in breast cancer. The research aims to validate these markers in a larger patient cohort and further develop them to be robust, accurate, and reliable diagnostic and prognostic markers for breast cancer. The authors of the study believe that the sphingolipid-based signatures identified in this study hold great promise to be used for diagnosis along with existing immunohistochemistry-based markers. Validations in a larger cohort will establish their use for prognosis and even identify key species that can be developed into therapeutic interventions. Last, but not least, developing sphingolipid-based non-invasive markers for breast cancer will be the next challenge that needs to be addressed soon.

Where do you seek scientific inspiration from?

My interest in the sciences began when I first observed a plant cell under a microscope. This sparked a curiosity in me to understand the complex mechanisms that govern life. I find great pleasure and fulfillment in uncovering new information, solving unresolved questions, and developing solutions that can contribute to the advancement of humanity. The works of renowned planetary scientist and communicator, Neil DeGrasse Tyson and Sir David Attenborough continue to inspire me in my passion for science. I am also deeply grateful for the guidance and inspiration provided by my guide, Dr. Avinash Bajaj, and co-guide, Dr. Ujjaini Dasgupta, who have encouraged me to take on new challenges and strive for excellence in scientific research.

How do you intend to help Indian science improve?

The Indian science sector has been making steady progress and expanding its horizons in various fields such as basic science, technology, medicine, agriculture, engineering, space, and climate research, thanks to the efforts of visionary scientists and top bureaucrats. However, there still exists a disconnect, often referred to as the “valley of death”, between patients, clinicians, scientists, industries, and regulatory authorities. Our focus is to bridge this gap and facilitate early diagnosis, knowledge transfer, and technology development to tackle diseases. Sustained scientific growth requires the cultivation of curious and innovative young minds, and we are dedicated to training the next generation of scientists to take on complex challenges in various fields.

Reference

Kar, A, Medatwal, N, Rajput, K, et al. Unique sphingolipid signature identifies luminal and triple-negative breast cancer subtypes. Int J Cancer. 2023; 1- 14. doi:10.1002/ijc.34423 https://onlinelibrary.wiley.com/doi/10.1002/ijc.34423

Copy Editor

Nikita Nimbark

PostGrad in Biotechnology

Nikita Completed her PostGrad in Biotechnology. She has interest in Bioinformatics. Her hobbies include travelling and calligraphy. She is always up for new challenges.

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