Combining gene expression signature with clinical features for survival stratification of gastric cancer

Sun, Qiang; Guo, Dongyang; Li, Shuang; Xu, Yanjun; Jiang, Mingchun; Li, Yang; Duan, Huilong; Zhuo, Wei; Liu, Wei; Zhu, Shankuan; Wang, Liangjing; Zhou, Tian

doi:10.1016/j.ygeno.2021.06.018

Cited by 8 publications

(7 citation statements)

References 53 publications

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“…The high-throughput sequencing technology offers an unprecedented view into tumor biology and the promise of personalized healthcare. Unbiased expression researches have been used to identify prognostic and predictive biomarkers in the form of individual signatures (57)(58)(59). However, these studies generally waste a large amount of signaling pathway knowledge that has been accumulated over decades of academic research (60).…”

Section: Discussionmentioning

confidence: 99%

Patient-Level DNA Damage Repair Pathway Profiles and Anti-Tumor Immunity for Gastric Cancer

et al. 2022

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DNA damage repair (DDR) comprises the detection and correction of alterations in the chemical structure of DNA. The dysfunction of the DDR process has been determined to have important implications for tumor carcinogenesis, malignancy progression, treatment resistance, and prognosis assessment. However, the role of the DDR process in gastric cancer (GC) remains to be fully understood. Thus, a total of 2,019 GC samples from our hospital (Harbin Medical University Cancer Hospital in china) and 12 public data sets were included in our study. In this study, single-sample gene set enrichment analysis (ssGSEA) was used to generate the DDR pathway activity profiles of 8 DDR sub-pathways and identify a DDR pathway signature by combining the DDR sub-pathway gene sets. The DDR pathway profiling’s impacts on the clinical outcomes, biological functions, genetic variants, immune heterogeneity, and treatment responses were analyzed through multidimensional genomics and clinical data. The results demonstrate that the DDR pathway profiling was clearly distinguished between tumor and normal tissues. The DDR pathway profiling reveals patient-level variations, which may contribute to explaining the high heterogeneity of human GC for the biological features and treatment outcomes. Thus, tumors with low DDR signature scores were independently correlated with shorter overall survival time and significantly associated with mesenchymal, invasion, and metastasis phenotypes. The statistical model integrating this DDR pathway signature with other clinical predictors outperforms each predictor alone for predicting overall survival in discrimination, calibration, and net clinical benefit. Moreover, low DDR signature scores were tightly associated with genome stability, characterized by low tumor mutational burden (TMB) and low fractions of genome alteration. Furthermore, this study confirms that patients with low DDR pathway signature scores might not benefit from adjuvant chemotherapy and a monoclonal antibody directed against programmed cell death-1 ligand 1 (anti-PD1) therapy. These findings highlighted that the DDR pathway profiling confers important implications for patients with GC and provides insights into the specific clinical and molecular features underlying the DDR process, which may help to facilitate clinical management.

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Section: Discussionmentioning

confidence: 99%

Patient-Level DNA Damage Repair Pathway Profiles and Anti-Tumor Immunity for Gastric Cancer

et al. 2022

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“…The testis-specific protein Y-encoded-like 5 (TSPYL5) is a member of the TSPYL family, and according to the current studies, the TSPYL5 expression is deleted or downregulated in many tumors [ 31 ]. As a new tumor suppressor molecule, the TSPYL5 is closely related to the malignant progression and prognosis of tumors [ 32 – 34 ] and has been reported to be associated with tumor differentiation, cell cycle, and survival in EC [ 35 , 36 ]. Although the roles of GRB7, KCNK9, MUC3A, and MYT1 in EC have not been exposed, their actions in other tumors have been investigated.…”

Section: Discussionmentioning

confidence: 99%

Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma

Wang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. PTEN mutations have been reported to be involved in the development and prognosis of endometrial carcinoma (EC). However, a prognostic gene signature associated with PTEN mutational status has not yet been developed. In this study, we generated a PTEN mutation-associated prognostic gene signature for EC. Methods. We obtained the single-nucleotide variation and transcriptomic profiling data from The Cancer Genome Atlas database as training data and implemented the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm to establish a PTEN mutation-associated prognostic gene signature. The overall survival rates of the high-risk and low-risk groups were determined with the Kaplan-Meier (K-M) method, and the accuracy of risk score prediction was tested by using the receiver operating characteristic (ROC) curve. Results. The K-M curves revealed that the EC patients with PTEN mutations augured favorable survival outcomes. Differential expression analysis between the EC patients with PTEN mutation and wild-type PTEN identified 224 differentially expressed genes (DEGs). Eighty-four DEGs that manifested prognostic value were fitted into the LASSO-Cox analysis, and a PTEN gene signature with seven mutation-associated prognostic genes that showed robust prognostic ability was constructed; this signature was then successfully validated in the other two datasets from the cBioPortal database as well as with 60 clinical specimens. Furthermore, the PTEN mutation-associated prognostic gene signature proved to be an independent prognostic predictor of EC. Remarkably, the EC patients in the high-risk group were characterized by higher tumor stages and grades as well as lower tumor mutation burden with respect to EC, with a poor survival outcome. Collectively, the PTEN mutation-associated prognostic gene signature that we developed could now be used as a favorable prognostic biomarker for EC. Conclusion. In summary, we developed and validated a prognostic predictor for EC associated with PTEN mutational status that may be used as a favorable prognostic biomarker and therapeutic target for EC.

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“…Tools belonging to this category: CanRisk [ 75 ], GenRisk [ 79 ], JASS [ 72 ], impute.me [ 73 ], Neptune, PRScs, SumHer [ 59 ].…”

Section: Classification Of Methods For Calculating Prsmentioning

confidence: 99%

“…Tools belonging to this category: AFA-Recur [ 82 ], CanRisk [ 75 ], GDM [ 77 ], SCFA [ 74 ], PXS [ 66 ].…”

Section: Classification Of Methods For Calculating Prsmentioning

confidence: 99%

A perspective on genetic and polygenic risk scores—advances and limitations and overview of associated tools

Schwarzerova,

Hurta,

Barton

et al. 2024

Briefings in Bioinformatics

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Polygenetic Risk Scores are used to evaluate an individual's vulnerability to developing specific diseases or conditions based on their genetic composition, by taking into account numerous genetic variations. This article provides an overview of the concept of Polygenic Risk Scores (PRS). We elucidate the historical advancements of PRS, their advantages and shortcomings in comparison with other predictive methods, and discuss their conceptual limitations in light of the complexity of biological systems. Furthermore, we provide a survey of published tools for computing PRS and associated resources. The various tools and software packages are categorized based on their technical utility for users or prospective developers. Understanding the array of available tools and their limitations is crucial for accurately assessing and predicting disease risks, facilitating early interventions, and guiding personalized healthcare decisions. Additionally, we also identify potential new avenues for future bioinformatic analyzes and advancements related to PRS.

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Combining gene expression signature with clinical features for survival stratification of gastric cancer

Cited by 8 publications

References 53 publications

Patient-Level DNA Damage Repair Pathway Profiles and Anti-Tumor Immunity for Gastric Cancer

Patient-Level DNA Damage Repair Pathway Profiles and Anti-Tumor Immunity for Gastric Cancer

Significance of a PTEN Mutational Status-Associated Gene Signature in the Progression and Prognosis of Endometrial Carcinoma

A perspective on genetic and polygenic risk scores—advances and limitations and overview of associated tools

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