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pmid:36281082

Identification and verification of a 4-gene signature predicting the overall survival of cervical cancer.

Lu Yuan · Zijun Lu · Guoqiang Sun · Dongmei Cao

Medicine · 2022 doi:10.1097/MD.0000000000031299

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complete

Experiment

complete

Data

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Identification and verification of a 4-gene signature predicting the overall survival of cervical cancer.
doi
10.1097/MD.0000000000031299
pmid
36281082
authors array · 4 items
[0]
Lu Yuan
[1]
Zijun Lu
[2]
Guoqiang Sun
[3]
Dongmei Cao
journal
Medicine
year
2022
abstract
Cervical cancer (CC) is one of the most common gynecological malignancies, ranking fourth in both incidence and mortality in women worldwide. Early screening and treatment are of great significance in reducing the incidence and mortality of CC. Due to the complex molecular mechanisms of tumor progression, the predictive power of traditional clinical information is limited. In this study, an effective molecular model is established to assess prognosis of patients with CC and guide clinical treatment so as to improve their survival rate. Three high quality datasets (GSE138080, GSE52904, GSE67522) of expression profiling were obtained from gene expression omnibus (GEO) database. Another mRNA expression and clinicopathological data of CC were obtained from The Cancer Genome Atlas (TCGA) dataset. The bioinformatic analyses such as univariate analysis, multivariate Cox proportional-hazards model (Cox) analysis and lasso regression analysis were conducted to select survival-related differentially expressed genes (DEGs) and further establish a prognostic gene signature. Moreover, the performance of prognostic gene signature was evaluated based on Kaplan-Meier curve and receiver operating characteristic (ROC) curve. Gene set enrichment analysis (GSEA) and tumor immunity analysis were carried out to elucidate the molecular mechanisms and immune relevance. A 4-gene signature comprising procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), spondin1 (SPON1), secreted phosphoprotein 1 (SPP1), ribonuclease H2 subunit A (RNASEH2A) was established to predict overall survival (OS) of CC. The ROC curve indicated good performance of the 4-gene signature in predicting OS of CC based on the TCGA dataset. The 4-gene signature classified the patients into high-risk and low-risk groups with distinct OS rates of CC. Univariate analysis and multivariate Cox regression analysis revealed that the 4-gene signature was an independent factor affecting the prognosis of patients with CC. Our study developed a 4-gene signature capable of predicting the OS of CC. The findings may be beneficial to individualized clinical treatment and timely follow-up for patients with CC.
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To investigate the prognostic value of the DEGs, univariate Cox proportional-hazards model (Cox) analysis was performed using survival package. To explore the prognostic model, Lasso and multivariate Cox regression analyses were performed to assess the relationship between prognostic DEGs expression and OS.
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sections[6] "2.4. Construction of prognostic model" paragraph 2
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To investigate the prognostic value of the DEGs, univariate Cox proportional-hazards model (Cox) analysis was performed using survival package. To explore the prognostic model, Lasso and multivariate Cox regression analyses were performed to assess the relationship between prognostic DEGs expression and OS.
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In the testing set, the area under curves for 1-, 3-, and 5-year OS predictions were 0.589, 0.626, and 0.710 (Fig. 4C), respective, while those were 0.680, 0.699, and 0.755 in the entire TCGA-CESC dataset, respectively (Fig. 4D).
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sections[14] "3.4. Validation of the performance of the 4-gene signature" paragraph 2
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In the testing set, the area under curves for 1-, 3-, and 5-year OS predictions were 0.589, 0.626, and 0.710 (Fig. 4C), respective, while those were 0.680, 0.699, and 0.755 in the entire TCGA-CESC dataset, respectively (Fig. 4D).
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In the testing set, the area under curves for 1-, 3-, and 5-year OS predictions were 0.589, 0.626, and 0.710 (Fig. 4C), respective, while those were 0.680, 0.699, and 0.755 in the entire TCGA-CESC dataset, respectively (Fig. 4D).
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The datasets generated during and/or analyzed during the current study are publicly available.The data were downloaded from GEO and TCGA database.
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The paper names GSE138080, GSE52904, GSE67522 in gene expression omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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To investigate the prognostic value of the DEGs, univariate Cox proportional-hazards model (Cox) analysis was performed using survival package. To explore the prognostic model, Lasso and multivariate Cox regression analyses were performed to assess the relationship between prognostic DEGs expression and OS.
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Due to the complex molecular mechanisms of tumor progression, the predictive power of traditional clinical information is limited. In this study, an effective molecular model is established to assess prognosis of patients with CC and guide clinical treatment so as to improve their survival rate. Three high quality datasets (GSE138080, GSE52904, GSE67522) of expression profiling were obtained from gene expression omnibus (GEO) database. Another mRNA expression and clinicopathological data of CC were obtained from The Cancer Genome Atlas (TCGA) dataset. The bioinformatic analyses such as univariate analysis, multivariate Cox proportional-hazards model (Cox) analysis and lasso regression analysis were conducted to select survival-related differentially expressed genes (DEGs) and further establish a prognostic gene signature. Moreover, the performance of prognostic gene signature was evaluated based on Kaplan-Meier curve and receiver operating characteristic (ROC) curve. Gene set enrichment analysis (GSEA) and tumor immunity analysis were carried out to elucidate the molecular mechanisms and immune relevance. A 4-gene signature comprising procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), spondin1 (SPON1), secreted phosphoprotein 1 (SPP1), ribonuclease H2 subunit A (RNASEH2A) was established to predict overall survival (OS) of CC. The ROC curve indicated good performance of the 4-gene signature in predicting OS of CC based on the TCGA dataset. The 4-gene signature classified the patients into high-risk and low-risk groups with distinct OS rates of CC. Univariate analysis and multivariate Cox regression analysis revealed that the 4-gene signature was an independent factor affecting the prognosis of patients with CC. Our study developed a 4-gene signature capable of predicting the OS of CC. The findings may be beneficial to individualized clinical treatment and timely follow-up for patients with CC.", "claims": [{"id": "claim-method", "statement": "To investigate the prognostic value of the DEGs, univariate Cox proportional-hazards model (Cox) analysis was performed using survival package. To explore the prognostic model, Lasso and multivariate Cox regression analyses were performed to assess the relationship between prognostic DEGs expression and OS.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36281082", "locator": "sections[6] \"2.4. Construction of prognostic model\" paragraph 2", "quote": "To investigate the prognostic value of the DEGs, univariate Cox proportional-hazards model (Cox) analysis was performed using survival package. 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