bims-ovdlit 2023-11-19 papers

Issue of 2023–11–19
four papers selected by
Lara Paracchini, Humanitas Research

Diagnostics (Basel). 2023 Oct 28. pii: 3331. [Epub ahead of print]13(21):

Current and Emerging Strategies for Tubo-Ovarian Cancer Diagnostics.

Mark R Brincat, Ana Rita Mira, Alexandra Lawrence.

Tubo-ovarian cancer is the most lethal gynaecological cancer. More than 75% of patients are diagnosed at an advanced stage, which is associated with poorer overall survival. Symptoms at presentation are vague and non-specific, contributing to late diagnosis. Multimodal risk models have improved the diagnostic accuracy of adnexal mass assessment based on patient risk factors, coupled with findings on imaging and serum-based biomarker tests. Newly developed ultrasonographic assessment algorithms have standardised documentation and enable stratification of care between local hospitals and cancer centres. So far, no screening test has proven to reduce ovarian cancer mortality in the general population. This review is an update on the evidence behind ovarian cancer diagnostic strategies.

Keywords: biomarkers; diagnosis; imaging; ovarian cancer; screening

DOI: https://doi.org/10.3390/diagnostics13213331

BMC Biol. 2023 Nov 13. 21(1): 253

Circulating cell-free DNA fragmentation is a stepwise and conserved process linked to apoptosis.

Dandan Zhu, Haihong Wang, Wei Wu, Shuaipeng Geng, Guolin Zhong, Yunfei Li, Han Guo, Guanghui Long, Qingqi Ren, Yi Luan, Chaohui Duan, Bing Wei, Jie Ma, Shiyong Li, Jun Zhou, Mao Mao.

BACKGROUND: Circulating cell-free DNA (cfDNA) is a pool of short DNA fragments mainly released from apoptotic hematopoietic cells. Nevertheless, the precise physiological process governing the DNA fragmentation and molecular profile of cfDNA remains obscure. To dissect the DNA fragmentation process, we use a human leukemia cell line HL60 undergoing apoptosis to analyze the size distribution of DNA fragments by shallow whole-genome sequencing (sWGS). Meanwhile, we also scrutinize the size profile of plasma cfDNA in 901 healthy human subjects and 38 dogs, as well as 438 patients with six common cancer types by sWGS.
RESULTS: Distinct size distribution profiles were observed in the HL60 cell pellet and supernatant, suggesting fragmentation is a stepwise process. Meanwhile, C-end preference was seen in both intracellular and extracellular cfDNA fragments. Moreover, the cfDNA profiles are characteristic and conserved across mammals. Compared with healthy subjects, distinct cfDNA profiles with a higher proportion of short fragments and lower C-end preference were found in cancer patients.
CONCLUSIONS: Our study provides new insight into fragmentomics of circulating cfDNA processing, which will be useful for early diagnosis of cancer and surveillance during cancer progression.

Keywords: Circulating cell-free DNA; End preference; Shallow whole-genome sequencing; Size profiling of cfDNA

DOI: https://doi.org/10.1186/s12915-023-01752-6

Front Immunol. 2023 ;14 1285540

Application of single-cell sequencing to the research of tumor microenvironment.

Sijie Chen, Zhiqing Zhou, Yu Li, Yuhui Du, Guoan Chen.

Single-cell sequencing is a technique for detecting and analyzing genomes, transcriptomes, and epigenomes at the single-cell level, which can detect cellular heterogeneity lost in conventional sequencing hybrid samples, and it has revolutionized our understanding of the genetic heterogeneity and complexity of tumor progression. Moreover, the tumor microenvironment (TME) plays a crucial role in the formation, development and response to treatment of tumors. The application of single-cell sequencing has ushered in a new age for the TME analysis, revealing not only the blueprint of the pan-cancer immune microenvironment, but also the heterogeneity and differentiation routes of immune cells, as well as predicting tumor prognosis. Thus, the combination of single-cell sequencing and the TME analysis provides a unique opportunity to unravel the molecular mechanisms underlying tumor development and progression. In this review, we summarize the recent advances in single-cell sequencing and the TME analysis, highlighting their potential applications in cancer research and clinical translation.

Keywords: clinical applications; immunological therapy; precision medicine; single-cell sequencing; tumor microenvironment

DOI: https://doi.org/10.3389/fimmu.2023.1285540

Cancer Treat Res. 2023 ;186 91-102

Clinical Use of PARP Inhibitors in BRCA Mutant and Non-BRCA Mutant Breast Cancer.

Filipa Lynce, Mark Robson.

The use of poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of patients with germline BRCA mutations (gBRCAm) and breast cancer, both in the early and advanced settings, is a success of genomically-directed treatment. These agents have been shown to be associated with longer progression-free survival when compared to standard chemotherapy, with an acceptable toxicity profile. A recent randomized trial demonstrated improved survival with the use of olaparib for 2 years compared to placebo in patients with early-stage high risk gBRCAm associated breast cancer. Ongoing research efforts are focused on identifying patients beyond those with BRCA1/2 or PALB2 mutations who may benefit from PARP inhibitors, exploring the overlapping mechanisms of resistance between platinum and PARP inhibitors and developing agents with less toxicity that will allow combinational strategies.

Keywords: BRCA1/2 mutations; Breast cancer; Homologous recombination deficiency (HRD); PARP inhibitors

DOI: https://doi.org/10.1007/978-3-031-30065-3_6