A New Stemness‐Related Prognostic Model for Predicting the Prognosis in Pancreatic Ductal Adenocarcinoma

Huang, Xiaoyan; Qin, Wentao; Su, Qingde; Qiu, Cheng-Cheng; Liu, Ruochuan; Xie, Shanshan; Hu, Yang; Zhu, Shang-Yong

doi:10.1155/2021/6669570

Cited by 6 publications

(5 citation statements)

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“…Recent studies have shown that mRNAsi has the ability to precisely measure the resemblance between cancer cells and stem cells, and genes associated with mRNAsi can serve as biomarker of cancer [60] . Our result indicated that PDAC patients with higher mRNAsi indices had poorer outcomes, which was consistent with previous studies [34] . In our present study, both stemness clusters and SFRGs model showed a favorable correlation with mRNAsi.…”

Section: Discussionsupporting

confidence: 93%

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Identification and validation of stemness-based and ferroptosis-related molecular clusters in pancreatic ductal adenocarcinoma

Ruan,

Wang,

Zhang

et al. 2024

Translational Oncology

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Section: Discussionsupporting

confidence: 93%

“… [33] and Huang et al. [34] identified stemness-related genes in PDAC through the utilization of weighted gene co-expression network analysis (WGCNA) and unsupervised clustering, based on differences in mRNA stemness index (mRNAsi). Subsequently, they established a prognostic model for predicting outcomes in PDAC.…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of stemness-based and ferroptosis-related molecular clusters in pancreatic ductal adenocarcinoma

Ruan,

Wang,

Zhang

et al. 2024

Translational Oncology

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“…Furthermore, cancer stemness has been demonstrated to be associated with kidney cancers, such as KIRC, but not for KICH, and negatively correlates with immune infiltrates (Xiao et al, 2021). Additionally, other studies demonstrated a stemness-related gene signature expression in cancers such as hepatocellular carcinoma, pancreatic ductal adenocarcinoma, and endometrial cancer as a novel prognostic marker for survival (Hong et al, 2021;Huang et al, 2021;Xu et al, 2021). In this study, we report a significant positive correlation between the expression profiles of the 13 mitochondrial gene signatures and stemness in KICH and LAML, as well as a negative correlation in THYM and UCEC.…”

Section: Discussionmentioning

confidence: 99%

A Sexual Bias in mitochondrial protein-coding gene expression across different tissues and the prognostic value in multiple cancers

Silva

Ferreira

Medina‐Acosta

2022

Preprint

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Mitochondria in mammalian cells provide ATP through oxidative phosphorylation. The overproduction of reactive oxygen species (ROS) in mitochondrial cells promotes cancer by modifying gene expression or function. Mating introduces competing mitochondrial (mtDNA) and nuclear DNA (nDNA) gene products, leading to biological differences between males and females for diseases and disorders such as cancer. There is a significant sex bias in aging-related conditions. We aimed to investigate whether sex and age affect mitochondrial protein-coding gene expression in cancer and, if so, to determine the prognosis value in survival outcomes, stemness, and immune cell infiltrates. We compared normal versus primary tumor transcriptomes (bulk RNA-Seq) from The Cancer Genome Atlas (TCGA), and the Genotype-Tissue Expression (GTEx) projects to test these hypotheses. Correlations between gene expression, survival, protective or risk factor, stemness, and immune cell infiltrate were performed in RStudio using UCSC Xena Shiny. Eleven mitochondrial protein-coding genes were altered in brain cancer (MT-ND2, MT-ND1, MT-ATP8, MT-ATP6, MT-CO2, MT-CYB, MT-CO3, MT-ND4L, MT-ND4, MT-ND3, MT-CO1). MT-ND5 and MT-ND6 are disproportionately expressed in female brain tissues. Mitochondrial global polymorphic expression sites of variation were more significant in the 50-59 and 60-79-year-old age groups than in the 20-49-year-old age groups. Pan-cancer survival analysis revealed a 4-component gene signature (MT-CO1, MT-CO2, MT-ND5, and MT-ND6) downregulated in low-grade glioma (LGG). This gene signature increased LGG overall survival, disease-specific survival, and progression-free interval without sex-specific association. However, the correlation with disease-free interval survival was female-specific. The 4-component gene signature was protective in LGG but risky in thymoma cancer and uterine corpus endometrial carcinoma. In LGG, the 4-component gene signature positively correlated with immune monocyte, NK, and B cell infiltrates and negatively correlated with T cell CD4+ Th2, macrophage M1 and M2, myeloid dendritic cell, and neutrophil. We identified a 13-component mitochondrial protein-coding gene signature associated with stemness in kidney chromophobe. A sex-biased effect was observed in mitochondrial protein-coding for brain tissues, with a female bias. However, an aging effect with higher polymorphic site expression was observed in male tissues. We conclude that the differentially expressed mitochondrial protein-coding genes provide new insights into carcinogenesis, helping to identify new prognostic markers. The overexpression of the 4-component gene signature is associated with a better prognosis in LGG, with positive and negative correlations with immune cell infiltrates.

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“…mRNAsi was found to be closely correlated with overall survival (OS) in pancreatic cancer, and patients with high mRNAsi values showed poor prognosis ( Tang et al, 2021 ). In addition, Huang et al (2021) established an mRNAsi-related prognostic model to successfully predict patient survival in pancreatic cancer. Moreover, multigene prognostic signatures based on the hypoxic microenvironment have been verified to be prognostic markers for pancreatic cancer and could be applied for risk stratification and clinical treatment ( Abou Khouzam et al, 2021 ; Chen et al, 2021 ; Ding et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a hypoxia-stemness-based prognostic signature in pancreatic adenocarcinoma

et al. 2022

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Background: Pancreatic adenocarcinoma (PAAD) is one of the most aggressive and fatal gastrointestinal malignancies with high morbidity and mortality worldwide. Accumulating evidence has revealed the clinical significance of the interaction between the hypoxic microenvironment and cancer stemness in pancreatic cancer progression and therapies. This study aims to identify a hypoxia-stemness index-related gene signature for risk stratification and prognosis prediction in PAAD.Methods: The mRNA expression-based stemness index (mRNAsi) data of PAAD samples from The Cancer Genome Atlas (TCGA) database were calculated based on the one-class logistic regression (OCLR) machine learning algorithm. Univariate Cox regression and LASSO regression analyses were then performed to establish a hypoxia-mRNAsi-related gene signature, and its prognostic performance was verified in both the TCGA-PAAD and GSE62452 corhorts by Kaplan-Meier and receiver operating characteristic (ROC) analyses. Additionally, we further validated the expression levels of signature genes using the TCGA, GTEx and HPA databases as well as qPCR experiments. Moreover, we constructed a prognostic nomogram incorporating the eight-gene signature and traditional clinical factors and analyzed the correlations of the risk score with immune infiltrates and immune checkpoint genes.Results: The mRNAsi values of PAAD samples were significantly higher than those of normal samples (p < 0.001), and PAAD patients with high mRNAsi values exhibited worse overall survival (OS). A novel prognostic risk model was successfully constructed based on the eight-gene signature comprising JMJD6, NDST1, ENO3, LDHA, TES, ANKZF1, CITED, and SIAH2, which could accurately predict the 1-, 3-, and 5-year OS of PAAD patients in both the training and external validation datasets. Additionally, the eight-gene signature could distinguish PAAD samples from normal samples and stratify PAAD patients into low- and high-risk groups with distinct OS. The risk score was closely correlated with immune cell infiltration patterns and immune checkpoint molecules. Moreover, calibration analysis showed the excellent predictive ability of the nomogram incorporating the eight-gene signature and traditional clinical factors.Conclusion: We developed a hypoxia-stemness-related prognostic signature that reliably predicts the OS of PAAD. Our findings may aid in the risk stratification and individual treatment of PAAD patients.

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A New Stemness‐Related Prognostic Model for Predicting the Prognosis in Pancreatic Ductal Adenocarcinoma

Cited by 6 publications

References 46 publications

Identification and validation of stemness-based and ferroptosis-related molecular clusters in pancreatic ductal adenocarcinoma

Identification and validation of stemness-based and ferroptosis-related molecular clusters in pancreatic ductal adenocarcinoma

A Sexual Bias in mitochondrial protein-coding gene expression across different tissues and the prognostic value in multiple cancers

Development and validation of a hypoxia-stemness-based prognostic signature in pancreatic adenocarcinoma

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