As a highly prevalent gastrointestinal malignant tumor, colorectal cancer poses a serious challenge in terms of increasing morbidity and mortality and late diagnosis due to the invisibility of the disease. Although existing therapies are diverse but limited in efficacy, the mechanism of programmed cell death (PCD) has become a focus of research due to its central role in maintaining body homeostasis and regulating tumor progression. Multimodal cell death pathways, such as apoptosis, autophagy, pyroptosis and ferroptosis, have shown unique advantages in inhibiting the proliferation and migration of colorectal cancer cells and enhancing the sensitivity to chemotherapy by responding to internal and external environmental stimuli. In recent years, natural products have risen to prominence by virtue of their multi-target synergistic effects and chemo-sensitizing properties, and have opened up a new direction for colorectal cancer treatment by precisely regulating the PCD pathway. In this paper, we searched PubMed, Web of Science and CNKI databases for relevant studies in the last 10 years using the keywords (Colorectal cancer) and (programmed cell death) and natural products. This work retrieved 59 studies (55 from the past 5 years and 4 from the past 10 years) to reveal the mechanism of action of natural products targeting PCD, aiming to provide theoretical support and practical guidance for the optimization of clinical therapeutic strategies and the development of innovative drugs.

Cancer is the main leading cause of death worldwide and poses a great threat to human life and health. Although pharmacological treatment with chemotherapy and immunotherapy is the main therapeutic strategy for cancer patients, there are still many shortcomings during the treatment such as incomplete killing of cancer cells and development of drug resistance. Emerging evidence indicates the promise of inducing ferroptosis for cancer treatment, particularly for eliminating aggressive malignancies that are resistant to conventional therapies. This review covers recent advances in important regulatory targets in the ferroptosis metabolic pathway and ferroptosis inducers (focusing mainly on the last 3 years) to delineate their design, mechanisms of action, and anticancer applications. To date, many compounds, including inhibitors, degraders, and active molecules from traditional Chinese medicine, have been demonstrated to have ferroptosis-inducing activity by targeting the different biomolecules in the ferroptosis pathway. However, strictly defined ferroptosis inducers have not yet been approved for clinical use; therefore, the discovery of new highly active, less toxic, and selective compounds remains the goal of further research in the coming years.

Colorectal cancer (CRC) is a serious threat to human health with the third morbidity and the second cancer-related mortality worldwide. It is urgent to explore more effective strategy for CRC because of the acquired treatment resistance from the non-surgical conventional therapies, including radiation, chemotherapy, targeted therapy and immunotherapy. Ferroptosis is a novel form of programmed cell death characterized by iron-dependent lipid peroxidation species (ROS) accumulation and has been identified as a promising target for cancer treatment, especially for those with treatment resistance. In this review, we mainly summarize the recent studies on the influence and regulation of ferroptosis by which (including gut microbiota) modulating the metabolism of iron, amino acid and lipid. Thus this analysis may provide potential targets for inducing CRC ferroptosis and shed lights on the future application of ferroptosis in CRC.

Phytochemical investigation on the aerial parts of Lysionotus pauciflorus Maxim. (Gesneriaceae), a medicinal plant used in Guangxi Zhuang Autonomous Region, China, resulted in the isolation of 13 secondary metabolites including two methoxyflavones, six flavonoid glycosides, and five caffeoyl phenylethanoid glycosides. Among these, the chemical structures of previously undescribed metabolites (1-3) were elucidated to be nevadensin 7-O-β-D-glucopyranosyl-(1 → 2)-β-D-glucopyranoside (1), nevadensin 7-O-β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranoside (2), and 2-(3,4-dihydroxyphenyl)ethyl-1-O-β-D-apiofuranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 3)-β-D-(6'-O-E-caffeoyl)glucopyranoside (3) by detailed spectroscopic and HPLC analyses. Inhibitory activity of isolated compounds against RSL3-induced ferroptosis on human hepatoma Hep3B cells were evaluated.

Whether N6-Methyladenosine (m6A)- and ferroptosis-related genes act on immune responses to regulate glioma progression remains unanswered. Data of glioma and corresponding normal brain tissues were fetched from the TCGA database and GTEx. Differentially expressed genes (DEGs) were identified for GO and KEGG enrichment analyses. The FerrDb database was based to yield ferroptosis-related DEGs. Hub genes were then screened out using the cytoHubba database and validated in clinical samples. Immune cells infiltrating into the glioma tissues were analysed using the CIBERSORT R script. The association of gene signature underlying the m6A-related ferroptosis with tumour-infiltrating immune cells and immune checkpoints in low-grade gliomas was analysed. Of 6298 DEGs enriched in mRNA modifications, 144 were ferroptosis-related; NFE2L2 and METTL16 showed the strongest positive correlation. METTL16 knockdown inhibited the migrative and invasive abilities of glioma cells and induced ferroptosis in vitro. NFE2L2 was enriched in the anti-m6A antibody. Moreover, METTL16 knockdown reduced the mRNA stability and level of NFE2L2 (both p < 0.05). Proportions of CD8+ T lymphocytes, activated mast cells and M2 macrophages differed between low-grade gliomas and normal tissues. METTL16 expression was negatively correlated with CD8+ T lymphocytes, while that of NFE2L2 was positively correlated with M2 macrophages and immune checkpoints in low-grade gliomas. Gene signatures involved in the m6A-related ferroptosis in gliomas were identified via bioinformatic analyses. NFE2L2 interacted with METTL16 to regulate the immune response in low-grade gliomas, and both molecules may be novel therapeutic targets for gliomas.

The nuclear factor-erythroid 2-related factor 2 (Nrf2) is able to control the redox balance in the cells responding to oxidative damage and other stress signals. The Nrf2 upregulation can elevate the levels of antioxidant enzymes to support against damage and death. In spite of protective function of Nrf2 in the physiological conditions, the stimulation of Nrf2 in the cancer has been in favour of tumorigenesis. Since the dysregulation of molecular pathways and mutations/deletions are common in tumors, Nrf2 can be a promising therapeutic target. The Nrf2 overexpression can prevent cell death in tumor and by increasing the survival rate of cancer cells, ensures the carcinogenesis. Moreover, the induction of Nrf2 can promote the invasion and metastasis of tumor cells. The Nrf2 upregulation stimulates EMT to increase cancer metastasis. Furthermore, regarding the protective function of Nrf2, its stimulation triggers chemoresistance. The natural products can regulate Nrf2 in the cancer therapy and reverse drug resistance. Moreover, nanostructures can specifically target Nrf2 signaling in cancer therapy. The current review discusses the potential function of Nrf2 in the proliferation, metastasis and drug resistance. Then, the capacity of natural products and nanostructures for suppressing Nrf2-mediated cancer progression is discussed.

This review aims to investigate the ferroptosis mechanism of fumarate hydratase (FH)-related tumors for the purpose of possible treatment of tumors. Ferroptosis is an iron (Fe)-dependent form of regulated cell death caused by lipid peroxidation on the cell membrane. Studies have implicated FH in tumorigenesis. As mutations in the FH gene alter cellular metabolism and increase tumorigenesis risk, particularly in the kidneys. As most tumor cells require higher amounts of ferrous ions (Fe2+) than normal cells, they are more susceptible to ferroptosis. Recent studies have indicated that ferroptosis is inhibited the pathogenesis and progression of FH-deficient tumors by regulating lipid and iron metabolism, glutathione-glutathione peroxidase 4 (GSH-GPX4), nuclear factor-erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) pathways. While the Fe2+ content is significantly lower in FH-deficient tumor cells, than that in normal cells. It is promising to promote ferroptosis by increasing the concentration of Fe2+ in cells to achieve the purpose of tumor treatment.

In this study, we searched for relevant articles on ferroptosis and FH-deficient tumors using PubMed database.

FH is a tumor suppressor. A number of basic studies have shown that the loss of FH plays an important role in hereditary leiomyomas and tumors such as renal cell carcinoma, ovarian cancer, and other tumors. This type of tumor cells can through induce ferroptosis, inhibit proliferation, migration and invasion of tumor cells, increase the sensitivity of tumor cells to chemotherapy, and reverse the drug resistance through various molecular mechanisms. At present, the research on ferroptosis in FH-related tumors is still in the basic experimental stage.

This article reviews the anti-tumor effects and mechanisms of FH and ferroptosis, in order to further explore the medical value of ferroptosis in FH-related tumor therapy.

Colorectal cancer (CRC) poses a significant global health challenge, ranking as the third most diagnosed cancer and the second leading cause of cancer-related deaths. Despite advancements in treatment, challenges such as delayed diagnosis, multidrug resistance, and limited therapeutic effectiveness persist, emphasizing the need for innovative approaches. This review explores the potential of natural products, nutraceuticals, and phytochemicals for targeting ferroptosis-related regulators as a novel strategy in CRC. Ferroptosis, a form of regulated cell death characterized by iron-dependent lethal lipid peroxide accumulation, holds substantial importance in CRC progression and therapy resistance. Natural products, known for their diverse bioactive effects and favorable safety profiles, emerge as promising candidates to induce ferroptosis in CRC cells. Exploring amino acid, iron, lipid metabolism regulators, and oxidative stress regulators reveals promising avenues for inducing cell death in CRC. This comprehensive review provides insights into the multifaceted effects of natural products on proteins integral to ferroptosis regulation, including GPX4, SLC7A11, ACSL4, NCOA4, and HO-1. By elucidating the intricate mechanisms through which natural products modulate these proteins, this review lays the foundation for a promising therapeutic strategy in CRC.

Colorectal cancer (CRC), a tumor of the digestive system, is characterized by high malignancy and poor prognosis. Currently, targeted therapy of CRC is far away from satisfying. The molecular mechanisms of regulated cell death (RCD) have been clearly elucidated, which can be intervened by drug or genetic modification. Numerous studies have provided substantial evidence linking these mechanisms to the progression and treatment of CRC. The RCD includes apoptosis, autophagy-dependent cell death (ADCD), ferroptosis, necroptosis, and pyroptosis, and immunogenic cell death, etc, which provide potential targets for anti-cancer treatment. For the last several years, small-molecule compounds targeting RCD have been a well concerned therapeutic strategy for CRC. This present review aims to describe the function of small-molecule compounds in the targeted therapy of CRC via targeting apoptosis, ADCD, ferroptosis, necroptosis, immunogenic dell death and pyroptosis, and their mechanisms. In addition, we prospect the application of newly discovered cuproptosis and disulfidptosis in CRC. Our review may provide references for the targeted therapy of CRC using small-molecule compounds targeting RCD, including the potential targets and candidate compounds.

In recent years, colorectal cancer incidence and mortality have increased significantly due to poor lifestyle choices. Despite the development of various treatments, their effectiveness against advanced/metastatic colorectal cancer remains unsatisfactory due to drug resistance. However, ferroptosis, a novel iron-dependent cell death process induced by lipid peroxidation and elevated reactive oxygen species (ROS) levels along with reduced activity of the glutathione peroxidase 4 (GPX4) antioxidant enzyme system, shows promise as a therapeutic target for colorectal cancer. This review aims to delve into the regulatory mechanisms of ferroptosis in colorectal cancer, providing valuable insights into potential therapeutic approaches. By targeting ferroptosis, new avenues can be explored for innovative therapies to combat colorectal cancer more effectively. In addition, understanding the molecular pathways involved in ferroptosis may help identify biomarkers for prognosis and treatment response, paving the way for personalized medicine approaches. Furthermore, exploring the interplay between ferroptosis and other cellular processes can uncover combination therapies that enhance treatment efficacy. Investigating the tumor microenvironment's role in regulating ferroptosis may offer strategies to sensitize cancer cells to cell death induction, leading to improved outcomes. Overall, ferroptosis presents a promising avenue for advancing the treatment of colorectal cancer and improving patient outcomes.

Background: Chemoresistance represented one of the challenges in the treatment of advanced gastric cancer (GC). Curcumol (CUR) was found to have a certain sensitizing effect on chemoresistance, although the mechanism was not yet fully understood. Purpose: To clarify the ability of CUR to intervene in the sensitivity of GC cells to Cisplatin (CDDP) by regulating the induction of ferroptosis through the P62/KEAP1/NRF2 pathway. Methods: An in vitro resistant cell line was established and treated with CUR for intervention. The synergy was evaluated using synergyfinder3.0 software. The impact of the combined use of CUR and CDDP on the proliferation, migration, and invasion of resistant GC cells was determined. The effect of CUR on ferroptosis in resistant GC cell lines was evaluated by measuring changes in reactive oxygen species (ROS) levels, malondialdehyde (MDA) levels, iron ion levels, and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Western blotting was used to verify the expression changes of the ferroptosis-related indicator GPX4 and the differential expression of the antioxidant-related pathway P62/KEAP1/NRF2, validating the mechanism by which CUR induces ferroptosis in resistant GC cells. In vivo validation was performed using a xenograft mouse model. Results: The evaluation by synergy3.0 revealed a synergistic effect between CUR and CDDP. After treatment with CUR and CDDP, resistant GC cell lines exhibited reduced proliferation, migration, and invasion capabilities. Furthermore, the resistant GC cell lines underwent ferroptosis, with significant changes observed in ferroptosis-related indicators such as ROS, MDA, iron ions, and GSH/GSSG. The ferroptosis-related targets Glutathione Peroxidase 4 (GPX4) and the antioxidant pathway P62/KEAP1/NRF2 signaling pathway also showed significant changes. In in vivo validation, the combination of CUR and CDDP inhibited the growth of subcutaneous tumors and was found to be associated with the inhibition of subcutaneous xenografts and the GPX4 and P62/KEAP1/NRF2 signaling pathways. Conclusion: This study first revealed that CUR enhanced the sensitivity of cisplatin-resistant GC cells to CDDP by inducing ferroptosis. The combination of CUR and CDDP induces ferroptosis in cisplatin-resistant GC through the P62/KEAP1/NRF2 pathway.

Curdione is a sesquiterpene isolated from Curcumae Rhizoma that possesses high biological activity and extensive pharmacological effects. As a traditional Chinese medicine, Curcumae Rhizoma can inhibit the development of many types of cancer, especially colorectal cancer. However, the anti-colorectal mechanism of its monomer curdione remains unclear.

Colorectal cancer (CRC) cells were treated with curdione at doses of 12.5 μM, 25 μM, and 50 μM, and then the cells' activity was measured with methyl thiazolyl tetrazolium (MTT). Nude mice were administered different doses of curdione subcutaneously and oxaliplatin by tail vein injection, and then hematoxylin-eosin (HE) staining was adopted to examine tumor histology. Moreover, flow cytometry was applied to detect reactive oxygen species in cells and tissues. Kits were employed to detect the levels of iron ions, malondialdehyde, lipid hydroperoxide, and glutathione. Polymerase chain reaction (PCR) and Western blotting were adopted to detect ferroptosis and m6A modification-related factors. A methylation spot hybridization assay was performed to measure changes in overall methylation. SLC7A11 and HOXA13 were measured by MeRIP-qPCR. The shRNA-METTL14 plasmid was constructed to verify the inhibitory effect of curdione on CRC.

A dose-dependent decrease in activity was observed in curdione-treated cells. Curdione increased the accumulation of reactive oxygen species in CRC cells and tumor tissues, greatly enhanced the levels of malondialdehyde, lipid hydroperoxide and Fe2+, and lowered the activity of glutathione. According to the qPCR and Western blot results, curdione promoted the expression of METTL14 and YTHDF2 in CRC cells and tissues, respectively, and decreased the expression of SLC7A11, SLC3A2, HOXA13, and glutathione peroxidase 4. Additionally, in animal experiments, the curdione-treated group showed severe necrosis of tumor cells, as displayed by HE staining. Furthermore, compared with the control group, levels of m6A modifying factors (namely, SLC7A11 and HOXA13) were increased in the tissues after drug intervention. METTL14 knockdown was followed by an increase in CRC cell activity and glutathione levels. However, the levels of reactive oxygen species, malondialdehyde, and iron ions decreased. The expression levels of SLC7A11, SLC3A2, HOXA13, and GPX4 were all increased after METTL14 knockdown.

The results suggest that curdione induces ferroptosis in CRC by virtue of m6A methylation.

Glucose-regulated protein 78 (GRP78) is frequently and highly expressed in various human malignancies and protects cancer cells against apoptosis induced by multifarious stresses, particularly endoplasmic reticulum stress (ER stress). The inhibition of GRP78 expression or activity could enhance apoptosis induced by anti-tumor drugs or compounds. Herein, we will evaluate the efficacy of lysionotin in the treatment of human liver cancer as well as the molecular mechanism. Moreover, we will examine whether inhibition of GRP78 enhanced the sensitivity of hepatocellular carcinoma cells to lysionotin. We found that lysionotin significantly suppressed proliferation and induced apoptosis of liver cancer cells. TEM showed that lysionotin-treated liver cancer cells showed an extensively distended and dilated endoplasmic reticulum lumen. Meanwhile, the levels of the ER stress hallmark GRP78 and UPR hallmarks (e.g., IRE1α and CHOP) were significantly increased in response to lysionotin treatment in liver cancer cells. Moreover, the reactive oxygen species (ROS) scavenger NAC and caspase-3 inhibitor Ac-DEVD-CHO visibly attenuated the induction of GRP78 and attenuated the decrease in cell viability induced by lysionotin. More importantly, the knockdown of GRP78 expression by siRNAs or treatment with EGCG, both induced remarkable increase in lysionotin-induced PARP and pro-caspase-3 cleavage and JNK phosphorylation. In addition, knockdown of GRP78 expression by siRNA or suppression GRP78 activity by EGCG both significantly improved the effectiveness of lysionotin. These data indicated that pro-survival GRP78 induction may contribute to lysionotin resistance. The combination of EGCG and lysionotin is suggested to represent a novel approach in cancer chemo-prevention and therapeutics.

Ferroptosis is a newly discovered form of programmed cell death caused by redox-active iron-mediated lipid peroxidation. Ferroptosis exhibits a unique morphological phenotype resulting from oxidative damage to membrane lipids. Ferroptosis induction has been shown to be effective in treating human cancers that rely on lipid peroxidation repair pathways. Nuclear factor erythroid 2-related factor 2 (Nrf2) can control the regulatory pathways of ferroptosis, which involve genes associated with glutathione biosynthesis, antioxidant responses, and lipid and iron metabolism. Resistant cancer cells often utilize Nrf2 stabilization by Keap1 inactivation or other somatic alterations in the genes from the Nrf2 pathway, which can confer resistance to ferroptosis induction and other therapies. However, pharmacological inactivation of the Nrf2 pathway can sensitize cancer cells to ferroptosis induction. Inducing lipid peroxidation and ferroptosis through regulating the Nrf2 pathway is a promising strategy for enhancing the anticancer effects of chemotherapy and radiation therapy in therapy-resistant human cancers. Despite promising preliminary studies, clinical trials in human cancer therapy have not yet been realized. A deeper understanding of their exact processes and efficacies in various cancers remains unsolved. Therefore, this article aims to summarize the regulatory mechanisms of ferroptosis, their modulation by Nrf2, and the potential of targeting Nrf2 for ferroptosis-based cancer therapy.

Ferroptosis is the cell death induced by ferrous ions and lipid peroxidation accumulation in tumor cells. Targeting ferroptosis, which is regulated by various metabolic and immune elements, might become a novel strategy for anti-tumor therapy. In this review, we will focus on the mechanism of ferroptosis and its interaction with cancer and tumor immune microenvironment, especially for the relationship between immune cells and ferroptosis. Also, we will discuss the latest preclinical progress of the collaboration between the ferroptosis-targeted drugs and immunotherapy, and the best potential conditions for their combined use. It will present a future insight on the possible value of ferroptosis in cancer immunotherapy.

Ferroptosis is a form of regulated cell death that is initiated by excessive lipid peroxidation that results in plasma membrane damage and the release of damage-associated molecular patterns. In recent years, ferroptosis has gained significant attention in cancer research due to its unique mechanism compared to other forms of regulated cell death, especially caspase-dependent apoptotic cell death. Gastrointestinal (GI) cancer encompasses malignancies that arise in the digestive tract, including the stomach, intestines, pancreas, colon, liver, rectum, anus, and biliary system. These cancers are a global health concern, with high incidence and mortality rates. Despite advances in medical treatments, drug resistance caused by defects in apoptotic pathways remains a persistent challenge in the management of GI cancer. Hence, exploring the role of ferroptosis in GI cancers may lead to more efficacious treatment strategies. In this review, we provide a comprehensive overview of the core mechanism of ferroptosis and discuss its function, regulation, and implications in the context of GI cancers.

Colorectal cancer (CRC) is the third highest incidence and the second highest mortality malignant tumor in the world. The etiology and pathogenesis of CRC are complex. Due to the long course of the disease and no obvious early symptoms, most patients are diagnosed as middle and late stages. CRC is prone to metastasis, most commonly liver metastasis, which is one of the leading causes of death in CRC patients. Ferroptosis is a newly discovered cell death form with iron dependence, which is driven by excessive lipid peroxides on the cell membrane. It is different from other form of programmed cell death in morphology and mechanism, such as apoptosis, pyroptosis and necroptosis. Numerous studies have shown that ferroptosis may play an important role in the development of CRC. For advanced or metastatic CRC, ferroptosis promises to open a new door in the setting of poor response to chemotherapy and targeted therapy. This mini review focuses on the pathogenesis of CRC, the mechanism of ferroptosis and the research status of ferroptosis in CRC treatment. The potential association between ferroptosis and CRC and some challenges are discussed.

Cigarette smoke (CS)-induced oxidative stress drives the pathogenesis of respiratory diseases, in which the activation and accumulation of reactive oxygen species (ROS) play an important role. Ferroptosis, a regulated cell death induced by Fe²⁺-dependent, lipid peroxidation, and ROS, is closely related to CS-induced airway injury disease, but its mechanism remains unclear. We found that bronchial epithelial ferroptosis and expression of iNOS in smoking patients were significantly higher than that in non-smokers. The iNOS, induced by CS exposure, was involved in bronchial epithelial cell ferroptosis, whereas genetic depletion or pharmacologic inactivation of iNOS attenuated the CS-induced ferroptosis and mitochondrial dysfunction. Our mechanistic studies found that SIRT3 directly bound to and negatively regulated iNOS to mediate ferroptosis. Moreover, we found that the Nrf-2/SIRT3 signal was deactivated by cigarette smoke extract (CSE)-induced ROS. Collectively, these results linked CS to human bronchial epithelial cell ferroptosis through ROS deactivation of the Nrf-2/SIRT3 signal to promote iNOS expression. Our study provides new insights into the pathogenesis of CS-induced tracheal injury diseases such as chronic bronchitis, emphysema, and chronic obstructive pulmonary disease.

Colorectal cancer (CRC) is the second deadliest cancer and the third-most common malignancy in the world. Surgery, chemotherapy, and targeted therapy have been widely used to treat CRC, but some patients still develop resistance to these treatments. Ferroptosis is a novel non-apoptotic form of cell death. It is an iron-dependent non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species and has been suggested to play a role in reversing resistance to anticancer drugs. This review summarizes recent advances in the prognostic role of ferroptosis in CRC and the mechanism of action in CRC.

Colorectal cancer (CRC) is the third most diagnosed and second leading cause of cancer-related death worldwide. Limitations with existing treatment regimens have demanded the search for better treatment options. Different phytochemicals with promising anti-CRC activities have been reported, with the molecular mechanism of actions still emerging. This review aims to summarize recent progress on the study of natural phenolic compounds in ameliorating CRC using in vivo models. This review followed the guidelines of the Preferred Reporting Items for Systematic Reporting and Meta-Analysis. Information on the relevant topic was gathered by searching the PubMed, Scopus, ScienceDirect, and Web of Science databases using keywords, such as "colorectal cancer" AND "phenolic compounds", "colorectal cancer" AND "polyphenol", "colorectal cancer" AND "phenolic acids", "colorectal cancer" AND "flavonoids", "colorectal cancer" AND "stilbene", and "colorectal cancer" AND "lignan" from the reputed peer-reviewed journals published over the last 20 years. Publications that incorporated in vivo experimental designs and produced statistically significant results were considered for this review. Many of these polyphenols demonstrate anti-CRC activities by inhibiting key cellular factors. This inhibition has been demonstrated by antiapoptotic effects, antiproliferative effects, or by upregulating factors responsible for cell cycle arrest or cell death in various in vivo CRC models. Numerous studies from independent laboratories have highlighted different plant phenolic compounds for their anti-CRC activities. While promising anti-CRC activity in many of these agents has created interest in this area, in-depth mechanistic and well-designed clinical studies are needed to support the therapeutic use of these compounds for the prevention and treatment of CRC.

Hepatocellular carcinoma (HCC) is a malignant disease with an increasing incidence and a high mortality rate. Ferroptosis, a novel type of cell death, has been reported to be closely associated with the progression of HCC. The aim of our study was to construct a novel ferroptosis-related signature (nFRGs) for prediction of prognosis, immune features and drug sensitivity of HCC patients. Data were obtained from the TCGA, ICGC, GSE104580, CCLE and IMvigor210 datasets, and the least absolute shrinkage and selection operator (LASSO) was used to construct nFRGs. In addition, the analyses involved in prognoses, molecular function, stemness indices, somatic mutation, responses to immunologic therapy, efficacy of transcatheter arterial chemoembolization (TACE) therapy and drug sensitivity were performed using diverse packages of R 4.1.3 between the low- and high-risk groups. The nFRGs included seven ferroptosis-related genes. Our results showed that nFRGs was an independent risk factor for prognoses of HCC patients, and HCC patients in the high-risk group presented with worse prognosis. Compared with the results of other studies, nFRGs was superior to other promising signatures in predicting prognoses of patients with HCC. In addition, most of the enriched pathways of differentially expressed genes (DEGs) between these subgroups were related to immune features. The molecular functions, genetic mutation and mRNAsi were varied between the high- and low-risk groups. Moreover, we observed significant immunosuppression state in the high-risk group. Patients in the high-risk group might benefit from immunotherapy, whereas patients in the low-risk group may be susceptible to TACE therapy. Finally, five sensitive drugs and four sensitive drugs were screened for patients in the high- and low-risk groups, respectively. nFRGs may served as a novel biomarker of prognosis and aid in personalized therapeutic strategies for patients with HCC.