Prognostic and therapeutic significance of a novel ferroptosis related signature in colorectal cancer patients

Du, Songtao; Zeng, Furong; Sun, Huiyan; Liu, Yanlong; Han, Peng; Zhang, Bomiao; Wang, Handong; Deng, Guangtong; Yin, Mingzhu; Cui, Binbin

doi:10.1080/21655979.2021.2017627

Cited by 27 publications

(23 citation statements)

References 35 publications

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“…Ferroptosis is a form of cell death that is morphologically and biochemically distinguished from apoptosis, classical necrosis, autophagy, and other forms of cell death. However, it also causes a decrease in cell number ( 15 ). Ferroptosis-related genes were identified by searching the keyword ferroptosis in the FerrDb database [ ; ( 16 )], the first database containing regulators and markers of disease-associated ferroptosis.…”

Section: Methodsmentioning

confidence: 99%

Effective prediction of potential ferroptosis critical genes in clinical colorectal cancer

et al. 2022

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BackgroundColon cancer is common worldwide, with high morbidity and poor prognosis. Ferroptosis is a novel form of cell death driven by the accumulation of iron-dependent lipid peroxides, which differs from other programmed cell death mechanisms. Programmed cell death is a cancer hallmark, and ferroptosis is known to participate in various cancers, including colon cancer. Novel ferroptosis markers and targeted colon cancer therapies are urgently needed. To this end, we performed a preliminary exploration of ferroptosis-related genes in colon cancer to enable new treatment strategies.MethodsFerroptosis-related genes in colon cancer were obtained by data mining and screening for differentially expressed genes (DEGs) using bioinformatics analysis tools. We normalized the data across four independent datasets and a ferroptosis-specific database. Identified genes were validated by immunohistochemical analysis of pathological and healthy clinical samples.ResultsWe identified DEGs in colon cancer that are involved in ferroptosis. Among these, five core genes were found: ELAVL1, GPX2, EPAS1, SLC7A5, and HMGB1. Bioinformatics analyses revealed that the expression of all five genes, except for EPAS1, was higher in tumor tissues than in healthy tissues.ConclusionsThe preliminary exploration of the five core genes revealed that they are differentially expressed in colon cancer, playing an essential role in ferroptosis. This study provides a foundation for subsequent research on ferroptosis in colon cancer.

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Section: Methodsmentioning

confidence: 99%

Effective prediction of potential ferroptosis critical genes in clinical colorectal cancer

et al. 2022

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“… 31 Peng et al explored a ferroptosis-related gene (FRG), Metallothionein-1G ( MG1T ), and demonstrated that CRC patients’ immune responses may be impacted by decreased levels of MG1T, which already showed a worse prognosis in CRC patients. 32 There are also some other FRGs screened from databases that are closely related to ferroptosis in CRC, for example, CYBB, YAP1 , 33 NFS1 , 34 TFAP2C, ALOX12, NOS2 , 35–37 NOX4 37 , 38 and so on. While these results may lack universality and need to be further verified.…”

Section: Regulation Of Ferroptosis In Crcmentioning

confidence: 99%

Ferroptosis: Reviewing CRC with the Third Eye

Liu

Tuerxun

et al. 2022

JIR

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Colorectal cancer (CRC) has been one of the most common cancers and maintains the second-highest incidence and mortality rates among all cancers. The high risk of recurrence and metastasis and poor survival are still huge challenges in CRC therapy, in which the discovery of ferroptosis provides a novel perspective. It has been ten years since a unique type of regulated cell death driven by iron accumulation and lipid peroxidation was proposed and named ferroptosis. During the past decade, there have been multiple pieces of evidence suggesting that ferroptosis participates in the pathophysiological processes during disease progression. In this review, we describe ferroptosis as an imbalance of oxidant systems and anti-oxidants which results in lipid peroxidation, membrane damage, and finally cell death. We elaborate on the mechanisms of ferroptosis and systematically summarize recent studies on the regulatory pathways of ferroptosis in CRC from various perspectives, ranging from encoding genes, noncoding RNAs to regulatory proteins. Finally, we discuss the potential therapeutic role of ferroptosis in CRC treatments.

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“…Ferroptosis, a type of iron-dependent cell death, is correlated with elevated levels of lipid peroxidation that were triggered by reactive oxygen species (ROS). Targeting ferroptosis-related molecules might offer tremendous potential for treating CRC [ 16 ]. RSL3 induces ferroptosis in CRC, while glutathione peroxidase 4 effectively reverses the effect [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Nodal promotes colorectal cancer survival and metastasis through regulating SCD1-mediated ferroptosis resistance

Wan

et al. 2023

Cell Death Dis

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Re-expression of an embryonic morphogen, Nodal, has been seen in several types of malignant tumours. By far, studies about Nodal’s role in colorectal cancer (CRC) remain limited. Ferroptosis is essential for CRC progression, which is caused by cellular redox imbalance and characterized by lipid peroxidation. Herein, we observed that Nodal enhanced CRC cell’s proliferative rate, motility, invasiveness, and epithelial–mesenchymal transition (EMT) in vivo and in vitro. Notably, Nodal overexpression induced monounsaturated fatty acids synthesis and increased the lipid unsaturation level. Nodal knockdown resulted in increased CRC cell lipid peroxidation. Stearoyl-coenzyme A desaturase 1 (SCD1) inhibition at least partially abolished the resistance of Nodal-overexpressing cells to RSL3-induced ferroptosis. Mechanistically, SCD1 was transcriptionally up-regulated by Smad2/3 pathway activation in response to Nodal overexpression. Significant Nodal and SCD1 up-regulation were observed in CRC tissues and were associated with CRC metastasis and poor clinical outcomes. Furthermore, bovine serum albumin nanoparticles/si-Nodal nanocomplexes targeting Nodal had anti-tumour effects on CRC progression and metastasis. This research elucidated the role of Nodal in CRC development and revealed a potential gene-based therapeutic strategy targeting Nodal for improving CRC treatment.

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Prognostic and therapeutic significance of a novel ferroptosis related signature in colorectal cancer patients

Cited by 27 publications

References 35 publications

Effective prediction of potential ferroptosis critical genes in clinical colorectal cancer

Effective prediction of potential ferroptosis critical genes in clinical colorectal cancer

Ferroptosis: Reviewing CRC with the Third Eye

Nodal promotes colorectal cancer survival and metastasis through regulating SCD1-mediated ferroptosis resistance

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