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Immune-related 3-lncRNA signature with prognostic connotation in a multi-cancer setting

journal contribution
submitted on 2024-04-16, 06:04 and posted on 2024-05-05, 09:57 authored by Shimaa Sherif, Raghvendra Mall, Hossam Almeer, Adviti Naik, Abdulaziz Al Homaid, Remy Thomas, Jessica Roelands, Sathiya Narayanan, Mahmoud Gasim Mohamed, Shahinaz Bedri, Salha Bujassoum Al-Bader, Kulsoom Junejo, Davide Bedognetti, Wouter Hendrickx, Julie Decock

Background

Advances in our understanding of the tumor microenvironment have radically changed the cancer field, highlighting the emerging need for biomarkers of an active, favorable tumor immune phenotype to aid treatment stratification and clinical prognostication. Numerous immune-related gene signatures have been defined; however, their prognostic value is often limited to one or few cancer types. Moreover, the area of non-coding RNA as biomarkers remains largely unexplored although their number and biological roles are rapidly expanding.

Methods

We developed a multi-step process to identify immune-related long non-coding RNA signatures with prognostic connotation in multiple TCGA solid cancer datasets.

Results

Using the breast cancer dataset as a discovery cohort we found 2988 differentially expressed lncRNAs between immune favorable and unfavorable tumors, as defined by the immunologic constant of rejection (ICR) gene signature. Mapping of the lncRNAs to a coding-non-coding network identified 127 proxy protein-coding genes that are enriched in immune-related diseases and functions. Next, we defined two distinct 20-lncRNA prognostic signatures that show a stronger effect on overall survival than the ICR signature in multiple solid cancers. Furthermore, we found a 3 lncRNA signature that demonstrated prognostic significance across 5 solid cancer types with a stronger association with clinical outcome than ICR. Moreover, this 3 lncRNA signature showed additional prognostic significance in uterine corpus endometrial carcinoma and cervical squamous cell carcinoma and endocervical adenocarcinoma as compared to ICR.

Conclusion

We identified an immune-related 3-lncRNA signature with prognostic connotation in multiple solid cancer types which performed equally well and in some cases better than the 20-gene ICR signature, indicating that it could be used as a minimal informative signature for clinical implementation.

Other Information

Published in: Journal of Translational Medicine
License: https://creativecommons.org/licenses/by/4.0
See article on publisher's website: https://dx.doi.org/10.1186/s12967-022-03654-7


Additional institutions affiliated with: Hamad Medical Corporation, Hamad General Hospital - HMC

Funding

Clonality and genomic immune signatures of infiltrating T-cells in Colorectal Carcinoma - https://app.dimensions.ai/details/grant/grant.6384668

History

Language

  • English

Publisher

Springer Nature

Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Qatar Computing Research Institute - HBKU
  • Qatar Biomedical Research Institute - HBKU
  • Cancer Research Center - QBRI
  • Sidra Medicine
  • Hamad Medical Corporation
  • Women's Wellness and Research Center - HMC
  • National Center for Cancer Care and Research - HMC
  • Weill Cornell Medicine - Qatar

Methodology

We developed a multi-step process to identify immune-related long non-coding RNA signatures with prognostic connotation in multiple TCGA solid cancer datasets.

Related Datasets

Roelands, Jessica; Mall, Raghvendra; Meer, Hossam Al; Thomas, Remy; Mohamed, Mahmoud G.; Bedri, Shahinaz; et al. (2020). Breast cancer Qatar dataset RA-QA. figshare. Dataset. https://doi.org/10.6084/m9.figshare.12901928.v1 Shimaa Sherif Khedr, & TBI and FCO labs @ Sidra Medicine Qatar. (2022). Sidra-TBI-FCO/IRlncRNA: Code accompanying the manuscript on ir-lncRNA signatures in cancer (V1.1). Zenodo. https://doi.org/10.5281/zenodo.7092234

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