bims-trytim 2024-05-19 papers

Issue of 2024–05–19
four papers selected by
Jialin Feng, University of Dundee

Aging Dis. 2024 May 08.

Disulfidptosis, A Novel Cell Death Pathway: Molecular Landscape and Therapeutic Implications.

Qiuyang Gu, Yumei An, Mingyuan Xu, Xinqi Huang, Xueshi Chen, Xianzhe Li, Haiyan Shan, Mingyang Zhang.

Programmed cell death is pivotal for several physiological processes, including immune defense. Further, it has been implicated in the pathogenesis of developmental disorders and the onset of numerous diseases. Multiple modes of programmed cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis, have been identified, each with their own unique characteristics and biological implications. In February 2023, Liu Xiaoguang and his team discovered "disulfidptosis," a novel pathway of programmed cell death. Their findings demonstrated that disulfidptosis is triggered in glucose-starved cells exhibiting high expression of a protein called SLC7A11. Furthermore, disulfidptosis is marked by a drastic imbalance in the NADPH/NADP+ ratio and the abnormal accumulation of disulfides like cystine. These changes ultimately lead to the destabilization of the F-actin network, causing cell death. Given that high SLC7A11 expression is a key feature of certain cancers, these findings indicate that disulfidptosis could serve as the basis of innovative anti-cancer therapies. Hence, this review delves into the discovery of disulfidptosis, its underlying molecular mechanisms and metabolic regulation, and its prospective applications in disease treatment.

DOI: https://doi.org/10.14336/AD.2024.0083

Int Immunopharmacol. 2024 May 13. pii: S1567-5769(24)00777-X. [Epub ahead of print]134 112258

The association between ferroptosis-related patterns and tumor microenvironment in colorectal cancer.

Chengshan He, Xuemei Gu, Chengyuan Dong, Zheng Xu, Luyao Liu, Bo Jiang, Yingying Lu, Xiudi Jiang, Zhicheng Lu.

Ferroptosis, a form of regulated cell death (RCD), exhibits distinct characteristics such as iron-dependence and lipid peroxidation accumulation (ROS), setting it apart from other types of cell death like apoptosis and necrosis. Its role in cancer biology is increasingly recognized, particularly its potential interaction with tumor microenvironment (TME) and CD8 T cells in cancer immunotherapy. However, the impact of ferroptosis on TME cell infiltration remains unclear. In this study, we conducted unsupervised clustering analysis on patient data from public databases, identifying three ferroptosis patterns with distinct TME cell infiltration characteristics: immune-inflamed, immune-excluded, and immune-desert phenotypes. We developed a ferroptosis score based on differentially expressed genes (DEGs) among these patterns, which correlated with various biological features including chemotherapy-resistance and immune cells infiltration. Despite patients with high ferroptosis scores exhibiting worse prognosis, they showed increased likelihood of benefiting from immunotherapy. Our findings highlight the importance of ferroptosis-related patterns in understanding TME cell infiltration and suggest novel strategies for drug combinations and immune-related therapies.

Keywords: CRC; Ferroptosis; Immunotherapy; TME

DOI: https://doi.org/10.1016/j.intimp.2024.112258

Cancers (Basel). 2024 Apr 24. pii: 1637. [Epub ahead of print]16(9):

Pentraxin 3: A Main Driver of Inflammation and Immune System Dysfunction in the Tumor Microenvironment of Glioblastoma.

Sarah Adriana Scuderi, Alessio Ardizzone, Ayomide Eniola Salako, Giuseppe Pantò, Fabiola De Luca, Emanuela Esposito, Anna Paola Capra.

Brain tumors are a heterogeneous group of brain neoplasms that are highly prevalent in individuals of all ages worldwide. Within this pathological framework, the most prevalent and aggressive type of primary brain tumor is glioblastoma (GB), a subtype of glioma that falls within the IV-grade astrocytoma group. The death rate for patients with GB remains high, occurring within a few months after diagnosis, even with the gold-standard therapies now available, such as surgery, radiation, or a pharmaceutical approach with Temozolomide. For this reason, it is crucial to continue looking for cutting-edge therapeutic options to raise patients' survival chances. Pentraxin 3 (PTX3) is a multifunctional protein that has a variety of regulatory roles in inflammatory processes related to extracellular matrix (ECM). An increase in PTX3 blood levels is considered a trustworthy factor associated with the beginning of inflammation. Moreover, scientific evidence suggested that PTX3 is a sensitive and earlier inflammation-related marker compared to the short pentraxin C-reactive protein (CRP). In several tumoral subtypes, via regulating complement-dependent and macrophage-associated tumor-promoting inflammation, it has been demonstrated that PTX3 may function as a promoter of cancer metastasis, invasion, and stemness. Our review aims to deeply evaluate the function of PTX3 in the pathological context of GB, considering its pivotal biological activities and its possible role as a molecular target for future therapies.

Keywords: glioblastoma; immune system; immunotherapy; inflammation; novel biomarkers; pentraxin 3

DOI: https://doi.org/10.3390/cancers16091637

Medicine (Baltimore). 2024 May 17. 103(20): e38193

Identification and characterization of ferroptosis-related genes in therapy-resistant gastric cancer.

Jieli Yu, Hua Li, Can Huang, Huoguo Chen.

Therapy resistance in gastric cancer poses ongoing challenges, necessitating the identification of ferroptosis-related genes linked to overall survival for potential therapeutic insights. The purpose of the study was to identify ferroptosis-related genes contributing to therapy resistance in gastric cancer and explore their associations with overall survival. Differentially expressed ferroptosis-related genes were identified in therapy-resistant versus therapy-responsive gastric cancer patients. Hub genes were selected from these genes. Enrichment analysis focused on oxidative stress and ROS metabolism. Validation was conducted in a TCGA stomach adenocarcinoma dataset. A hub gene-based risk model (DUSP1/TNF/NOX4/LONP1) was constructed and assessed for overall survival prediction. Associations with the tumor immune microenvironment were examined using the ESTIMATE algorithm and correlation analysis. Ten hub genes were identified, enriched in oxidative stress and ROS metabolism. Validation confirmed their aberrant expressions in the TCGA dataset. The hub gene-based risk model effectively predicted overall survival. High G6PD/TNF expression and low NOX4/SREBF1/MAPK3/DUSP1/KRAS/SIRT3/LONP1 expression correlated with stromal and immune scores. KRAS/TNF/MAPK3 expression positively correlated with immune-related SREBF1/NOX4 expression. DUSP1/NOX4/SREBF1/TNF/KRAS expression was associated with immune cell infiltration. The hub gene-based risk model (DUSP1/TNF/NOX4/LONP1) shows promise as an overall survival predictor in gastric cancer. Ferroptosis-related hub genes represent potential therapeutic targets for overcoming therapy resistance in gastric cancer treatment.

DOI: https://doi.org/10.1097/MD.0000000000038193