Identification of Diagnostic Genes and Effective Drugs Associated with Osteoporosis Treatment by Single-Cell RNA-Seq Analysis and Network Pharmacology

Zhang, Zhanyue; Zhang, Tingbao; Zhou, Liangshuang; Guan, Jianzhong

doi:10.1155/2022/6830635

Cited by 4 publications

(2 citation statements)

References 42 publications

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“…These analyses aimed to assess whether the risk score could serve as a reliable prognostic factor, independent of conventional clinicopathological characteristics. The “rms” R package ( Zhang et al, 2022 ) was employed to construct a nomogram incorporating the risk score and clinicopathological features. This nomogram provided a visual tool for predicting the survival of patients in the TCGA-UVM cohort, enabling clinicians to estimate individual patient prognoses more accurately.…”

Section: Methodsmentioning

confidence: 99%

Decoding tumor heterogeneity in uveal melanoma: basement membrane genes as novel biomarkers and therapeutic targets revealed by multi-omics approaches for cancer immunotherapy

Li,

Cai,

Yang

et al. 2023

Front. Pharmacol.

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Background: Uveal melanoma (UVM) is a primary intraocular malignancy that poses a significant threat to patients’ visual function and life. The basement membrane (BM) is critical for establishing and maintaining cell polarity, adult function, embryonic and organ morphogenesis, and many other biological processes. Some basement membrane protein genes have been proven to be prognostic biomarkers for various cancers. This research aimed to develop a novel risk assessment system based on BMRGs that would serve as a theoretical foundation for tailored and accurate treatment.Methods: We used gene expression profiles and clinical data from the TCGA-UVM cohort of 80 UVM patients as a training set. 56 UVM patients from the combined cohort of GSE84976 and GSE22138 were employed as an external validation dataset. Prognostic characteristics of basement membrane protein-related genes (BMRGs) were characterized by Lasso, stepwise multifactorial Cox. Multivariate analysis revealed BMRGs to be independent predictors of UVM. The TISCH database probes the crosstalk of BMEGs in the tumor microenvironment at the single-cell level. Finally, we investigated the function of ITGA5 in UVM using multiple experimental techniques, including CCK8, transwell, wound healing assay, and colony formation assay.Results: There are three genes in the prognostic risk model (ADAMTS10, ADAMTS14, and ITGA5). After validation, we determined that the model is quite reliable and accurately forecasts the prognosis of UVM patients. Immunotherapy is more likely to be beneficial for UVM patients in the high-risk group, whereas the survival advantage may be greater for UVM patients in the low-risk group. Knockdown of ITGA5 expression was shown to inhibit the proliferation, migration, and invasive ability of UVM cells in vitro experiments.Conclusion: The 3-BMRGs feature model we constructed has excellent predictive performance which plays a key role in the prognosis, informing the individualized treatment of UVM patients. It also provides a new perspective for assessing pre-immune efficacy.

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Section: Methodsmentioning

confidence: 99%

Decoding tumor heterogeneity in uveal melanoma: basement membrane genes as novel biomarkers and therapeutic targets revealed by multi-omics approaches for cancer immunotherapy

Li,

Cai,

Yang

et al. 2023

Front. Pharmacol.

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“…To evaluate the proficiency of risk scores as standalone prognostic indicators and subsequently construct related nomograms, analyses invoking both univariate and multivariate Cox regression methodologies were undertaken. In the realm of the TCGA-ccRCC collective, we harnessed the "rms" package (26) within the R software to construct a columnar illustration, embodying risk evaluations concurrent with clinicopathological characteristics, designed to project survival prospects at intervals of 1, 3, and 5 years.…”

Section: Nomogram Constructionmentioning

confidence: 99%

Elucidating the Influence of MPT-driven necrosis-linked LncRNAs on immunotherapy outcomes, sensitivity to chemotherapy, and mechanisms of cell death in clear cell renal carcinoma

Huang,

Liu,

Chen

et al. 2023

Front. Oncol.

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BackgroundClear cell renal carcinoma (ccRCC) stands as the prevailing subtype among kidney cancers, making it one of the most prevalent malignancies characterized by significant mortality rates. Notably,mitochondrial permeability transition drives necrosis (MPT-Driven Necrosis) emerges as a form of cell death triggered by alterations in the intracellular microenvironment. MPT-Driven Necrosis, recognized as a distinctive type of programmed cell death. Despite the association of MPT-Driven Necrosis programmed-cell-death-related lncRNAs (MPTDNLs) with ccRCC, their precise functions within the tumor microenvironment and prognostic implications remain poorly understood. Therefore, this study aimed to develop a novel prognostic model that enhances prognostic predictions for ccRCC.MethodsEmploying both univariate Cox proportional hazards and Lasso regression methodologies, this investigation distinguished genes with differential expression that are intimately linked to prognosis.Furthermore, a comprehensive prognostic risk assessment model was established using multiple Cox proportional hazards regression. Additionally, a thorough evaluation was conducted to explore the associations between the characteristics of MPTDNLs and clinicopathological features, tumor microenvironment, and chemotherapy sensitivity, thereby providing insights into their interconnectedness.The model constructed based on the signatures of MPTDNLs was verified to exhibit excellent prediction performance by Cell Culture and Transient Transfection, Transwell and other experiments.ResultsBy analyzing relevant studies, we identified risk scores derived from MPTDNLs as an independent prognostic determinant for ccRCC, and subsequently we developed a Nomogram prediction model that combines clinical features and associated risk assessment. Finally, the application of experimental techniques such as qRT-PCR helped to compare the expression of MPTDNLs in healthy tissues and tumor samples, as well as their role in the proliferation and migration of renal clear cell carcinoma cells. It was found that there was a significant correlation between CDK6-AS1 and ccRCC results, and CDK6-AS1 plays a key role in the proliferation and migration of ccRCC cells. Impressive predictive results were generated using marker constructs based on these MPTDNLs.ConclusionsIn this research, we formulated a new prognostic framework for ccRCC, integrating mitochondrial permeability transition-induced necrosis. This model holds significant potential for enhancing prognostic predictions in ccRCC patients and establishing a foundation for optimizing therapeutic strategies.

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Divergent associations of inflammatory markers with bone turnover markers in elderly patients with osteoporotic fractures

Xu,

Guo,

Guo

et al. 2024

Sci Rep

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The association between inflammatory markers (IMs) and bone turnover markers (BTMs) in osteoporotic fracture patients has not been comprehensively studied. Therefore, this study examined the correlation between the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), or Monocyte-to-lymphocyte ratio (MLR) and BTMs in osteoporosis (OP) fracture patients. This retrospective cross-sectional study analyzed 740 OP fracture patients admitted to the hospital from January 2017 to July 2022. MLR, NLR, and PLR were calculated based on each patient’s complete blood count. The relationship between IMs and BTMs was assessed using three models by adjusting variables. Furthermore, the potential curve relationship between IMs and BTMs was also determined via the threshold effect analysis and curve fittings. In addition, stratified analysis was performed on each adjusted variable to confirm the stability of the results. After adjusting the variables, the results showed that NLR was negatively correlated with procollagen type 1 N-terminal propeptide (P1NP) (β = -1.1788, 95% CI: -1.7230 to -0.6345, P -value < 0.0001) and β-C-terminal telopeptide of type I collagen (β-CTX) (β = -0.0104, 95% CI: -0.0145 to -0.0062, P -value < 0.0001), Furthermore, MLR was negatively correlated with P1NP (β = -17.4523, 95% CI: -27.7335 to -7.1710, P -value = 0.0009) and β-CTX (β = -0.1327, 95% CI: -0.2211 to -0.0443, P -value = 0.0034). However, PLR indicated a positive correlation with P1NP (β = 0.0326, 95% CI: 0.0007 to 0.0645, P -value = 0.0458) and β-CTX (β = 0.0003, 95% CI: 0.0001 to 0.0006, P -value = 0.0204). The threshold effect analysis and curve fittings revealed the presence of a turning point between NLR, MLR, and P1NP, β-CTX. In addition, the stratified analysis validated the result’s stability. In conclusion, this study indicates a negative correlation between NLR and MLR with P1NP, while PLR shows a positive correlation with P1NP. Additionally, NLR and MLR exhibit a negative correlation with β-CTX, whereas PLR demonstrates a positive correlation with β-CTX. Further research is required to assess the intricate mechanisms linking IM with bone metabolism. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-024-75704-7.

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Identification of Diagnostic Genes and Effective Drugs Associated with Osteoporosis Treatment by Single-Cell RNA-Seq Analysis and Network Pharmacology

Cited by 4 publications

References 42 publications

Decoding tumor heterogeneity in uveal melanoma: basement membrane genes as novel biomarkers and therapeutic targets revealed by multi-omics approaches for cancer immunotherapy

Decoding tumor heterogeneity in uveal melanoma: basement membrane genes as novel biomarkers and therapeutic targets revealed by multi-omics approaches for cancer immunotherapy

Elucidating the Influence of MPT-driven necrosis-linked LncRNAs on immunotherapy outcomes, sensitivity to chemotherapy, and mechanisms of cell death in clear cell renal carcinoma

Divergent associations of inflammatory markers with bone turnover markers in elderly patients with osteoporotic fractures

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