bims-ectoca 2024-12-08 papers

Issue of 2024–12–08
three papers selected by
Ankita Daiya, OneCell Diagnostics Inc.

Signal Transduct Target Ther. 2024 Dec 04. 9(1): 340

Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.

Yang Chen, Rui Liang, Yong Li, Lingli Jiang, Di Ma, Qing Luo, Guanbin Song.

The dynamic regulation of chromatin accessibility is one of the prominent characteristics of eukaryotic genome. The inaccessible regions are mainly located in heterochromatin, which is multilevel compressed and access restricted. The remaining accessible loci are generally located in the euchromatin, which have less nucleosome occupancy and higher regulatory activity. The opening of chromatin is the most important prerequisite for DNA transcription, replication, and damage repair, which is regulated by genetic, epigenetic, environmental, and other factors, playing a vital role in multiple biological progresses. Currently, based on the susceptibility difference of occupied or free DNA to enzymatic cleavage, solubility, methylation, and transposition, there are many methods to detect chromatin accessibility both in bulk and single-cell level. Through combining with high-throughput sequencing, the genome-wide chromatin accessibility landscape of many tissues and cells types also have been constructed. The chromatin accessibility feature is distinct in different tissues and biological states. Research on the regulation network of chromatin accessibility is crucial for uncovering the secret of various biological processes. In this review, we comprehensively introduced the major functions and mechanisms of chromatin accessibility variation in different physiological and pathological processes, meanwhile, the targeted therapies based on chromatin dynamics regulation are also summarized.

DOI: https://doi.org/10.1038/s41392-024-02030-9

J Clin Invest. 2024 Nov 21. pii: e171164. [Epub ahead of print]

YAP1 induces bladder cancer progression and promotes immune evasion through IL-6/ STAT3 pathway and CXCL deregulation.

Pritam Sadhukhan, Mingxiao Feng, Emily J Illingworth, Ido Sloma, Akira Ooki, Andres Matoso, David Sidransky, Burles A Johnson Rd, Luigi Marchionni, Fenna Cm Sillé, Woonyoung Choi, David J McConkey, Mohammad Obaidul Hoque.

The Hippo signaling pathway plays a key role in tumorigenesis in different cancer types. We investigated the role of the Hippo "effector" YAP1 on the tumor immune microenvironment (TIME) of urothelial carcinoma of bladder (UCB) and evaluated the efficacy of immunotherapy in the context of YAP1 signaling. We performed numerous in vitro and in vivo experiments to determine the role of YAP1 using genetic and pharmacological attenuation of YAP1 activity. Briefly, RNA sequencing was carried out with mice and human cell lines to identify novel YAP1-regulated downstream targets unbiasedly. We then experimentally confirmed that YAP1 regulates the TIME through the IL-6/STAT3 signaling pathway and varied C-X-C motif chemokine regulation. We analyzed several human sample sets to explore the TIME status in the context of YAP1 expression. Our data indicate that YAP1 attenuation decreases M2 macrophages and MDSCs in the TIME compared to YAP1 expressing cells. In summary, this study provides insights on YAP1 signaling as a driver for cancer stemness and an inducer of immunosuppressive TIME. Moreover, the therapeutic efficacy of YAP1 attenuation indicates that combined blockade of YAP1 and immune checkpoints may yield clinical value for treating UCB patients.

Keywords: Cancer immunotherapy; Oncogenes; Oncology; Therapeutics; Tumor suppressors

DOI: https://doi.org/10.1172/JCI171164

BMC Cancer. 2024 Dec 03. 24(1): 1491

Circulating Tumor cells and multiple indicators combined to identify the risk of poorer prognosis in patients with resected non-small cell lung cancer.

Jinghan Song, Xiong Ye, Qianqian Peng, Xinnan Ying, Hui Xiao.

BACKGROUND: Surgical resection is an important treatment option for patients with non-small cell lung cancer (NSCLC). However, recurrence and survival rates remain a cause of concern. To further improve prognosis, more studies have focused on liquid biopsy, which has significant value as a prognostic factor for defining the risk stratification of postoperative NSCLC patients. This study aimed to identify circulating tumor cells (CTCs) as biomarkers that indicate a poor prognosis, combined with multiple indicators to determine prognostic risks in advance and develop individualized treatment strategies.
METHODS: Between November 2015 and August 2018, 65 radical resected patients with NSCLC were analyzed. Preoperative CTCs were collected, and follow-up lasted until August 2023. Overall survival (OS) and disease-free survival (DFS) were the primary outcomes.
RESULTS: With an 11 CTC unit threshold, the high preoperative CTC level group had worse OS and DFS than the low-level group, suggesting that preoperative CTC levels have prognostic value. Time-dependent receiver operating characteristic (ROC) curves also showed satisfactory predictive efficiency of CTCs. Univariate analysis revealed that preoperative CTC levels were significantly associated with increasing risks for OS and DFS. Moreover, we combined CTCs and multiple indicators to provide a reference for a group at high risk of adverse outcomes.
CONCLUSIONS: CTCs serve as feasible biomarkers for predicting postoperative prognosis in NSCLC patients. The combination of hematological, radiological, and pathological features could be valuable tools to guide postoperative management and treatment decisions in these patients. A multimodal prognostic approach is important for the clinical evaluation of lung cancer.

Keywords: Circulating tumor cells; Lung cancer; Prognosis; Radiological analysis; Tumor markers

DOI: https://doi.org/10.1186/s12885-024-13245-y