Identification of a Six-Gene Signature for Predicting the Overall Survival of Cervical Cancer Patients

Huo, Xiao; Zhou, Xiaoshuang; Peng, Peng; Yu, Mei; Zhang, Ying; Yang, Jiaxin; Cao, Dongyan; Sun, Hengzi; Shen, Keng

doi:10.2147/ott.s276553

Cited by 12 publications

(5 citation statements)

References 44 publications

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“…Among the 21 candidate genes, ADAMTS10, ANGPTL5, APCDD1L, CCDC85A, CGREF1, CHRDL2, DENND5B, EFS, P4HA3PCD, H20, PCDHAC2, RASGRF2, SLC6A14, TESC, TNMD, and ZNF229 have not been reported in CC; our study is the first to characterize these genes as a prognostic signature. SLC19A3, CRP, and FGF8 have been reported to have clinical prognostic value in CC progression [34]; our study is the first to characterize SLC19A3 as a prognostic signature through NAD+ metabolism. TFPI has been reported to be related to survival in breast cancer [35].…”

Section: Discussionmentioning

confidence: 65%

Prediction of Cervical Cancer Outcome by Identifying and Validating a NAD+ Metabolism-Derived Gene Signature

Chen¹,

Jing²,

Qiu³

et al. 2022

JPM

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Cervical cancer (CC) is the second most common female cancer. Excellent clinical outcomes have been achieved with current screening tests and medical treatments in the early stages, while the advanced stage has a poor prognosis. Nicotinamide adenine dinucleotide (NAD+) metabolism is implicated in cancer development and has been enhanced as a new therapeutic concept for cancer treatment. This study set out to identify an NAD+ metabolic-related gene signature for the prospect of cervical cancer survival and prognosis. Tissue profiles and clinical characteristics of 293 cervical cancer patients and normal tissues were downloaded from The Cancer Genome Atlas database to obtain NAD+ metabolic-related genes. Based on the differentially expressed NAD+ metabolic-related genes, cervical cancer patients were divided into two subgroups (Clusters 1 and 2) using consensus clustering. In total, 1404 differential genes were acquired from the clinical data of these two subgroups. From the NAD+ metabolic-related genes, 21 candidate NAD+ metabolic-related genes (ADAMTS10, ANGPTL5, APCDD1L, CCDC85A, CGREF1, CHRDL2, CRP, DENND5B, EFS, FGF8, P4HA3, PCDH20, PCDHAC2, RASGRF2, S100P, SLC19A3, SLC6A14, TESC, TFPI, TNMD, ZNF229) were considered independent indicators of cervical cancer prognosis through univariate and multivariate Cox regression analyses. The 21-gene signature was significantly different between the low- and high-risk groups in the training and validation datasets. Our work revealed the promising clinical prediction value of NAD+ metabolic-related genes in cervical cancer.

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Section: Discussionmentioning

confidence: 65%

Prediction of Cervical Cancer Outcome by Identifying and Validating a NAD+ Metabolism-Derived Gene Signature

Chen¹,

Jing²,

Qiu³

et al. 2022

JPM

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“…Similarly, amplified furin expression has been revealed in gynecologic malignancies, especially in cervical and breast cancer, based on the Cancer Genome Atlas (TCGA) studies. It is considered either a poor prognostic marker or a proto-oncogene [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Furin and Chronic Inflammation in the Progression of Cervical Intraepithelial Neoplasia to Cancer: A Cross-Sectional Study

Afsar,

Turan,

Guney

et al. 2023

Cancers

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Objective: The current study aimed to delineate the relationship between furin and chronic inflammation while cervical intraepithelial neoplasia progresses to cancer. Study Design: This cross-sectional study included 81 women who required colposcopic examinations. The study groups were formed based on pathological results: Group I included women with cervical intraepithelial neoplasia (CIN) I (n = 30); Group II included women with CIN II-III (n = 28); and Group III included women with cervical cancer (CC) (n = 23). Furin, ki-67, and p16 levels were evaluated based on immunostaining intensity. The inflammatory indices were calculated in parallel with the literature from routine blood samples retrieved within one week before the procedure. Results: Furin expression gradually increased from CIN I to CIN II-III and from CIN II-III to CC, respectively (p < 0.001, p = 0.005). NLR, MLR, PLR, and SII were significantly higher in the CC group (p < 0.001). ROC curve analysis unveiled that NLR, MLR, PLR, and SII predicted the presence of CC with a cutoff value of 2.39 for NLR (sensitivity: 91.3%, specificity: 63.8%, AUROC: 0.79, p < 0.001); a cutoff value of 0.27 for MLR (sensitivity: 78.3%, specificity: 72.4%, AUROC: 0.77, p = 0.009); a cutoff value of 123 for PLR (sensitivity: 100%, specificity: 41.4%, AUROC: 0.70, p = 0.04); and a cutoff value of 747 for SII (sensitivity: 69.6%, specificity: 90.7%, AUROC: 0.71, p = 0.014). Conclusion: Furin expression increased gradually in parallel with the severity of cervical intraepithelial neoplasia. The inflammatory indices were higher in the presence of CC and denoted a good discrimination ability for predicting cervical cancer.

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“…Wang Q et al reported that METTL3 enhanced the HK2 stability through the YTHDF1-mediated m6A modification, thus promoting the Warburg effect of CC, which might shed new light on CC treatment [ 34 ]. Additionally, Xiao H et al indicated that SLC22A3 up-regulation predicted the dismal prognosis of CC patients [ 35 ]. However, although the overexpression of SLC22A3 is related to the high mortality risk of CC patients, its expression levels in normal cervical cells are dramatically higher than those in cancer patients.…”

Section: Discussionmentioning

confidence: 99%

CircRNA-Based Cervical Cancer Prognosis Model, Immunological Validation and Drug Prediction

et al. 2022

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Background: Cervical cancer (CC) is a common cancer in female, which is associated with problems like poor prognosis. Circular RNA (circRNA) is a kind of competing endogenous RNA (ceRNA) that has an important role in regulating microRNA (miRNA) in many cancers. The regulatory mechanisms of CC immune microenvironment and the transcriptome level remain to be fully explored. Methods: In this study, we constructed the ceRNA network through the interaction data and expression matrix of circRNA, miRNA and mRNA. Meanwhile, based on the gene expression matrix, CIBERSORT algorithm was used to reveal contents of tumor-infiltrating immune cells (TIICs). Then, we screened prognostic markers based on ceRNA network and immune infiltration and constructed two nomograms. In order to find immunological differences between the high- and low-risk CC samples, we examined multiple immune checkpoints and predicted the effect of PD-L1 ICI immunotherapy. In addition, the sensitive therapeutics for high-risk patients were screened, and the potential agents with anti-CC activity were predicted by Connective Map (CMap). Results: We mapped a ceRNA network including 5 circRNAs, 17 miRNAs and 129 mRNAs. From the mRNA nodes of the network six genes and two kind of cells were identified as prognostic makers for CC. Among them, there was a significant positive correlation between CD8+ T cells and SNX10 gene. The results of TIDE and single sample GSEA (ssGSEA) showed that T cells CD8 do play a key role in inhibiting tumor progression. Further, our study screened 24 drugs that were more sensitive to high-risk CC patients and several potential therapeutic agents for reference. Conclusions: Our study identified several circRNA-miRNA-mRNA regulatory axes and six prognostic genes based on the ceRNA network. In addition, through TIIC, survival analysis and a series of immunological analyses, T cells were proved to be good prognostic markers, besides play an important role in the immune process. Finally, we screened 24 potentially more effective drugs and multiple potential drug compounds for high- and low-risk patients.

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Identification of a Six-Gene Signature for Predicting the Overall Survival of Cervical Cancer Patients

Cited by 12 publications

References 44 publications

Prediction of Cervical Cancer Outcome by Identifying and Validating a NAD+ Metabolism-Derived Gene Signature

Prediction of Cervical Cancer Outcome by Identifying and Validating a NAD+ Metabolism-Derived Gene Signature

The Relationship between Furin and Chronic Inflammation in the Progression of Cervical Intraepithelial Neoplasia to Cancer: A Cross-Sectional Study

CircRNA-Based Cervical Cancer Prognosis Model, Immunological Validation and Drug Prediction

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