Prognostic Assessment of Oxidative Stress-Related Genes in Colorectal Cancer and New Insights into Tumor Immunity

Chen, Zilu; Mei, Kun; Xiao, Yao; Xiong, Yan; Long, Wei; Wang, Qin; Zhong, Jiang; Di, Dongmei; Ge, Yunxi; Luo, Yi; Li, Ziyun; Huang, Yan; Gu, Renjun; Wang, Bin

doi:10.1155/2022/2518340

Cited by 6 publications

(4 citation statements)

References 46 publications

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“…Researches have shown that OSGIN2 may be involved in the physiological processes of cancer and other diseases 13 , 14 . Chen Z et al 21 also observed high expression of OSGIN2 in colorectal cancer tissues. Our study confirmed the association of OSGIN2 with gastric cancer and suggested it as a potential marker for the diagnosis and prognosis of GC by bioinformatics analysis and experimental validation.…”

Section: Discussionmentioning

confidence: 90%

Clinical prognostic value of OSGIN2 in gastric cancer and its proliferative effect in vitro

Wang

Zhu

Jia

et al. 2023

Sci Rep

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This study explored the promoting effect of oxidative stress-induced growth inhibitor family member 2(OSGIN2) on gastric cancer (GC) through public databases and in vitro experiments. The potential relationship between OSGIN2 expression, prognosis, functional enrichment of associated differential genes, immune infiltration, and mutational information in gastric cancer were comprehensively investigated using bioinformatics analysis. OSGIN2 was knocked down using small interfering RNA (siRNA) transfection for subsequent cell function testing. The results showed that gastric carcinoma cells and tissues contained high levels of OSGIN2, which was associated with a poor prognosis for GC patients. It was important in the cell cycle, autophagy, etc., and was related to a variety of tumor-related signal pathways. Knockdown of OSGIN2 inhibited tumor cell proliferation and contributed to cell cycle arrest. It was also correlated with tumor immune infiltrating cells (TILs), affecting antitumor immune function. Our analysis highlights that OSING2, as a new biomarker, has diagnostic and prognostic value in gastric cancer and is a potentially effective target in GC treatment.

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Section: Discussionmentioning

confidence: 90%

Clinical prognostic value of OSGIN2 in gastric cancer and its proliferative effect in vitro

Wang

Zhu

Jia

et al. 2023

Sci Rep

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“… 41 AARS2 contributes to mitochondrial respiration and has been identified as a protective factor in the prognostic model of colorectal cancer. 42 Zhu et al suggested a gene signature containing AARS2 and VARS2 via involving mitochondrial respiration and proliferation in COAD. 43 VARS2 polymorphisms were found in a candidate prognostic marker for early breast cancer 44 and were associated with mitochondrial respiratory chain and oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Prognostic Model for Colon Adenocarcinoma Depending on Nuclear-Mitochondrial-Related Genes

Lv,

Huang,

et al. 2024

Technol Cancer Res Treat

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Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4+ memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.

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“…Although CBS and CSE may contribute to the synthesis of H 2 S under physiological conditions, their substantial contributions depend on the activity levels of this enzyme expressed in different cells and tissues as well as under various cellular metabolic conditions [ 1 , 2 , 9 , 36 , 37 , 38 , 39 ]. For example, these canonical enzymes and Cars2 are known to be highly expressed in cancer tissues such as human Basal-like breast cancers and colorectal cancer tissues [ 40 , 41 ]. In the breast cancer tissues where CBS and CSE are highly expressed, CBS and CSE play important roles in sulfur metabolism and tumorigenesis [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism

et al. 2023

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Reactive sulfur species, or persulfides and polysulfides, such as cysteine hydropersulfide and glutathione persulfide, are endogenously produced in abundance in both prokaryotes and eukaryotes, including mammals. Various forms of reactive persulfides occur in both low-molecular-weight and protein-bound thiols. The chemical properties and great supply of these molecular species suggest a pivotal role for reactive persulfides/polysulfides in different cellular regulatory processes (e.g., energy metabolism and redox signaling). We demonstrated earlier that cysteinyl-tRNA synthetase (CARS) is a new cysteine persulfide synthase (CPERS) and is responsible for the in vivo production of most reactive persulfides (polysulfides). Some researchers continue to suggest that 3-mercaptopyruvate sulfurtransferase (3-MST), cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) may also produce hydrogen sulfide and persulfides that may be generated during the transfer of sulfur from 3-mercaptopyruvate to the cysteine residues of 3-MST or direct synthesis from cysteine by CBS/CSE, respectively. We thus used integrated sulfur metabolome analysis, which we recently developed, with 3-MST knockout (KO) mice and CBS/CSE/3-MST triple-KO mice, to elucidate the possible contribution of 3-MST, CBS, and CSE to the production of reactive persulfides in vivo. We therefore quantified various sulfide metabolites in organs derived from these mutant mice and their wild-type littermates via this sulfur metabolome, which clearly revealed no significant difference between mutant mice and wild-type mice in terms of reactive persulfide production. This result indicates that 3-MST, CBS, and CSE are not major sources of endogenous reactive persulfide production; rather, CARS/CPERS is the principal enzyme that is actually involved in and even primarily responsible for the biosynthesis of reactive persulfides and polysulfides in vivo in mammals.

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Prognostic Assessment of Oxidative Stress-Related Genes in Colorectal Cancer and New Insights into Tumor Immunity

Cited by 6 publications

References 46 publications

Clinical prognostic value of OSGIN2 in gastric cancer and its proliferative effect in vitro

Clinical prognostic value of OSGIN2 in gastric cancer and its proliferative effect in vitro

A Comprehensive Prognostic Model for Colon Adenocarcinoma Depending on Nuclear-Mitochondrial-Related Genes

Synthesis of Sulfides and Persulfides Is Not Impeded by Disruption of Three Canonical Enzymes in Sulfur Metabolism

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