Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers

Shan, Dan-Dan; Zheng, Qiuxian; Chen, Zhi

doi:10.4251/wjgo.v14.i10.1892

Cited by 3 publications

(2 citation statements)

References 65 publications

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“…This study demonstrates that GINS2 affected the proliferation, clone formation, stemness, migration, and invasion of glioma cells, as reported in other cancers as well [ 38 ]. In addition, we discovered for the first time that GINS2 regulated drug sensitivity in tumor cells.…”

Section: Discussionsupporting

confidence: 85%

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GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas

He,

Liang,

Jiang

et al. 2024

Cell Death Dis

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Temozolomide (TMZ), a DNA alkylating agent, has become the primary treatment for glioma, the most common malignancy of the central nervous system. Although TMZ-containing regimens produce significant clinical response rates, some patients inevitably suffer from inferior treatment outcomes or disease relapse, likely because of poor chemosensitivity of glioma cells due to a robust DNA damage response (DDR). GINS2, a subunit of DNA helicase, contributes to maintaining genomic stability and is highly expressed in various cancers, promoting their development. Here, we report that GINS2 was upregulated in TMZ-treated glioma cells and co-localized with γH2AX, indicating its participation in TMZ-induced DDR. Furthermore, GINS2 regulated the malignant phenotype and TMZ sensitivity of glioma cells, mostly by promoting DNA damage repair by affecting the mRNA stability of early growth response factor 1 (EGR1), which in turn regulates the transcription of epithelial cell-transforming sequence 2 (ECT2). We constructed a GINS2–EGR1–ECT2 prognostic model, which accurately predicted patient survival. Further, we screened Palbociclib/BIX-02189 which dampens GINS2 expression and synergistically inhibits glioma cell proliferation with TMZ. These findings delineate a novel mechanism by which GINS2 regulates the TMZ sensitivity of glioma cells and propose a promising combination therapy to treat glioma.

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Section: Discussionsupporting

confidence: 85%

“…GINS2 has been reported to be highly expressed in various tumors [ 38 ]. To explore the role of GINS2 in the development of glioma, we examined the mRNA and protein expression of GINS2 in seven glioma cell lines.…”

Section: Resultsmentioning

confidence: 99%

GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas

He,

Liang,

Jiang

et al. 2024

Cell Death Dis

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The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci

Wei,

Li,

Zhou

et al. 2024

Open Medicine

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Backgrounds Glioma is a highly malignant brain tumor with a grim prognosis. Genetic factors play a role in glioma development. While some susceptibility loci associated with glioma have been identified, the risk loci associated with prognosis have received less attention. This study aims to identify risk loci associated with glioma prognosis and establish a prognostic prediction model for glioma patients in the Chinese Han population. Methods A genome-wide association study (GWAS) was conducted to identify risk loci in 484 adult patients with glioma. Cox regression analysis was performed to assess the association between GWAS-risk loci and overall survival as well as progression-free survival in glioma. The prognostic model was constructed using LASSO Cox regression analysis and multivariate Cox regression analysis. The nomogram model was constructed based on the single nucleotide polymorphism (SNP) classifier and clinical indicators, enabling the prediction of survival rates at 1-year, 2-year, and 3-year intervals. Additionally, the receiver operator characteristic (ROC) curve was employed to evaluate the prediction value of the nomogram. Finally, functional enrichment and tumor-infiltrating immune analyses were conducted to examine the biological functions of the associated genes. Results Our study found suggestive evidence that a total of 57 SNPs were correlated with glioma prognosis (p < 5 × 10−5). Subsequently, we identified 25 SNPs with the most significant impact on glioma prognosis and developed a prognostic model based on these SNPs. The 25 SNP-based classifier and clinical factors (including age, gender, surgery, and chemotherapy) were identified as independent prognostic risk factors. Subsequently, we constructed a prognostic nomogram based on independent prognostic factors to predict individualized survival. ROC analyses further showed that the prediction accuracy of the nomogram (AUC = 0.956) comprising the 25 SNP-based classifier and clinical factors was significantly superior to that of each individual variable. Conclusion We identified a SNP classifier and clinical indicators that can predict the prognosis of glioma patients and established a prognostic prediction model in the Chinese Han population. This study offers valuable insights for clinical practice, enabling improved evaluation of patients’ prognosis and informing treatment options.

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Identification of Key Immune and Cell Cycle Modules and Prognostic Genes for Glioma Patients through Transcriptome Analysis

Guo,

Yang,

Jiang

et al. 2024

Pharmaceuticals

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Background: Gliomas, the most prevalent type of primary brain tumor, stand out as one of the most aggressive and lethal types of human cancer. Methods & Results: To uncover potential prognostic markers, we employed the weighted correlation network analysis (WGCNA) on the Chinese Glioma Genome Atlas (CGGA) 693 dataset to reveal four modules significantly associated with glioma clinical traits, primarily involved in immune function, cell cycle regulation, and ribosome biogenesis. Using the least absolute shrinkage and selection operator (LASSO) regression algorithm, we identified 11 key genes and developed a prognostic risk score model, which exhibits precise prognostic prediction in the CGGA 325 dataset. More importantly, we also validated the model in 12 glioma patients with overall survival (OS) ranging from 4 to 132 months using mRNA sequencing and immunohistochemical analysis. The analysis of immune infiltration revealed that patients with high-risk scores exhibit a heightened immune infiltration, particularly immune suppression cells, along with increased expression of immune checkpoints. Furthermore, we explored potentially effective drugs targeting 11 key genes for gliomas using the library of integrated network-based cellular signatures (LINCS) L1000 database, identifying that in vitro, both torin-1 and clofarabine exhibit promising anti-glioma activity and inhibitory effect on the cell cycle, a significant pathway enriched in the identified glioma modules. Conclusions: In conclusion, our study provides valuable insights into molecular mechanisms and identifying potential therapeutic targets for gliomas.

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Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers

Cited by 3 publications

References 65 publications

GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas

GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas

The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci

Identification of Key Immune and Cell Cycle Modules and Prognostic Genes for Glioma Patients through Transcriptome Analysis

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