bims-ovdlit 2022-04-24 papers

Issue of 2022–04–24
four papers selected by
Lara Paracchini, Humanitas Research

Diagnostics (Basel). 2022 Apr 13. pii: 978. [Epub ahead of print]12(4):

Cell-Free DNA Fragmentomics in Liquid Biopsy.

Cell-free DNA (cfDNA) in bodily fluids has rapidly transformed the development of noninvasive prenatal testing, cancer liquid biopsy, and transplantation monitoring. Plasma cfDNA consists of a mixture of molecules originating from various bodily tissues. The study of the fragmentation patterns of cfDNA, also referred to as 'fragmentomics', is now an actively pursued area of biomarker research. Clues that cfDNA fragmentation patterns might carry information concerning the tissue of origin of cfDNA molecules have come from works demonstrating that circulating fetal, tumor-derived, and transplanted liver-derived cfDNA molecules have a shorter size distribution than the background mainly of hematopoietic origin. More recently, an improved understanding of cfDNA fragmentation has provided many emerging fragmentomic markers, including fragment sizes, preferred ends, end motifs, single-stranded jagged ends, and nucleosomal footprints. The intrinsic biological link between activities of various DNA nucleases and characteristic fragmentations has been demonstrated. In this review, we focus on the biological properties of cell-free DNA unveiled recently and their potential clinical applications.

Keywords: NIPT; cancer detection; cell-free DNA; fragmentomics; liquid biopsy

DOI: https://doi.org/10.3390/diagnostics12040978

Nat Med. 2022 Apr;28(4): 666-677

The future of early cancer detection.

Rebecca C Fitzgerald, Antonis C Antoniou, Ljiljana Fruk, Nitzan Rosenfeld.

A proactive approach to detecting cancer at an early stage can make treatments more effective, with fewer side effects and improved long-term survival. However, as detection methods become increasingly sensitive, it can be difficult to distinguish inconsequential changes from lesions that will lead to life-threatening cancer. Progress relies on a detailed understanding of individualized risk, clear delineation of cancer development stages, a range of testing methods with optimal performance characteristics, and robust evaluation of the implications for individuals and society. In the future, advances in sensors, contrast agents, molecular methods, and artificial intelligence will help detect cancer-specific signals in real time. To reduce the burden of cancer on society, risk-based detection and prevention needs to be cost effective and widely accessible.

DOI: https://doi.org/10.1038/s41591-022-01746-x

Cancer Cell Int. 2022 Apr 19. 22(1): 155

Technique integration of single-cell RNA sequencing with spatially resolved transcriptomics in the tumor microenvironment.

Hailan Yan, Jinghua Shi, Yi Dai, Xiaoyan Li, Yushi Wu, Jing Zhang, Zhiyue Gu, Chenyu Zhang, Jinhua Leng.

BACKGROUND: The tumor microenvironment contributes to tumor initiation, growth, invasion, and metastasis. The tumor microenvironment is heterogeneous in cellular and acellular components, particularly structural features and their gene expression at the inter-and intra-tumor levels.
MAIN TEXT: Single-cell RNA sequencing profiles single-cell transcriptomes to reveal cell proportions and trajectories while spatial information is lacking. Spatially resolved transcriptomics redeems this lack with limited coverage or depth of transcripts. Hence, the integration of single-cell RNA sequencing and spatial data makes the best use of their strengths, having insights into exploring diverse tissue architectures and interactions in a complicated network. We review applications of integrating the two methods, especially in cellular components in the tumor microenvironment, showing each role in cancer initiation and progression, which provides clinical relevance in prognosis, optimal treatment, and potential therapeutic targets.
CONCLUSION: The integration of two approaches may break the bottlenecks in the spatial resolution of neighboring cell subpopulations in cancer, and help to describe the signaling circuitry about the intercommunication and its exact mechanisms in producing different types and malignant stages of tumors.

Keywords: Integration; Single-cell RNA sequencing; Spatially resolved transcriptomics; Tumor microenvironment

DOI: https://doi.org/10.1186/s12935-022-02580-4