Journal of Clinical Medicine

Research

19 pages, 14388 KiB

Open AccessArticle

Identification of a Novel Cuproptosis-Related Gene Signature and Integrative Analyses in Thyroid Cancer

by Jiapeng Huang, Jinyuan Shi, Pu Wu, Wei Sun, Dalin Zhang, Zhihong Wang, Xiaoyu Ji, Chengzhou Lv, Ting Zhang, Ping Zhang and Hao Zhang

J. Clin. Med. 2023, 12(5), 2014; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12052014 - 3 Mar 2023

Cited by 5 | Viewed by 1783

Abstract

Cuproptosis is a novel programmed cell death that depends on copper. The role and potential mechanism of cuproptosis-related genes (CRGs) in thyroid cancer (THCA) are still unclear. In our study, we randomly divided THCA patients from the TCGA database into a training set [...] Read more.

Cuproptosis is a novel programmed cell death that depends on copper. The role and potential mechanism of cuproptosis-related genes (CRGs) in thyroid cancer (THCA) are still unclear. In our study, we randomly divided THCA patients from the TCGA database into a training set and a testing set. A cuproptosis-related signature consisting of six genes (SLC31A1, LIAS, DLD, MTF1, CDKN2A, and GCSH) was constructed using the training set to predict the prognosis of THCA and was verified with the testing set. All patients were classified into low- and high-risk groups according to risk score. Patients in the high-risk group had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) values for 5 years, 8 years, and 10 years were 0.845, 0.885, and 0.898, respectively. The tumor immune cell infiltration and immune status were significantly higher in the low-risk group, which indicated a better response to immune checkpoint inhibitors (ICIs). The expression of six cuproptosis-related genes in our prognostic signature were verified by qRT-PCR in our THCA tissues, and the results were consistent with TCGA database. In summary, our cuproptosis-related risk signature has a good predictive ability regarding the prognosis of THCA patients. Targeting cuproptosis may be a better alternative for THCA patients. Full article

(This article belongs to the Special Issue New Advances in Clinical Genetics and Genetic Epidemiology)

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13 pages, 12394 KiB

Open AccessArticle

by Hanwen Su, Youyi Liu and Jingtao Huang

J. Clin. Med. 2023, 12(5), 1715; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12051715 - 21 Feb 2023

Cited by 3 | Viewed by 1587

Abstract

(1) Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis is an iron-dependent cell death program that plays a regulatory role in HBV infection and HCC [...] Read more.

(1) Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis is an iron-dependent cell death program that plays a regulatory role in HBV infection and HCC development. It is necessary to classify the roles of ferroptosis or ferroptosis-related genes (FRGs) in HBV-related HCC progression. (2) Methods: We conducted a matched case–control study from the TCGA database, retrospectively collecting demographic data and common clinical indicators from all subjects. The Kaplan–Meier curve, univariate and multivariate cox regression analysis of the FRGs were used to explore the risk factors for HBV-related HCC. The CIBERSORT algorithm and TIDE algorithm were executed to evaluate the functions of FRGs in the tumor-immune environment. (3) Results: A total of 145 HBV-positive HCC patients and 266 HBV-negative HCC patients were enrolled in our study. Four ferroptosis related genes (FANCD2, CS, CISD1 and SLC1A5) were positively correlated with the progression of HBV-related HCC. Among them, SLC1A5 was an independent risk factor for HBV-related HCC, and correlated with poor prognosis, advanced progression and an immunosuppression microenvironment. (4) Conclusions: Here, we revealed that a ferroptosis-related gene, SLC1A5, may be an excellent predictor of HBV-related HCC and may provide insight into the development of innovative possible therapeutic techniques. Full article

(This article belongs to the Special Issue New Advances in Clinical Genetics and Genetic Epidemiology)

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12 pages, 609 KiB

Open AccessArticle

Causal Inference of Central Nervous System-Regulated Hormones in COVID-19: A Bidirectional Two-Sample Mendelian Randomization Study

by Yuxuan Sun, Ziyi Ding, Yawei Guo, Jinqiu Yuan, Chengming Zhu, Yihang Pan and Rui Sun

J. Clin. Med. 2023, 12(4), 1681; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12041681 - 20 Feb 2023

Cited by 2 | Viewed by 2213

Abstract

We assessed the causal association of three COVID-19 phenotypes with insulin-like growth factor 1, estrogen, testosterone, dehydroepiandrosterone (DHEA), thyroid-stimulating hormone, thyrotropin-releasing hormone, luteinizing hormone (LH), and follicle-stimulating hormone. We used bidirectional two-sample univariate and multivariable Mendelian randomization (MR) analyses to evaluate the direction, [...] Read more.

We assessed the causal association of three COVID-19 phenotypes with insulin-like growth factor 1, estrogen, testosterone, dehydroepiandrosterone (DHEA), thyroid-stimulating hormone, thyrotropin-releasing hormone, luteinizing hormone (LH), and follicle-stimulating hormone. We used bidirectional two-sample univariate and multivariable Mendelian randomization (MR) analyses to evaluate the direction, specificity, and causality of the association between CNS-regulated hormones and COVID-19 phenotypes. Genetic instruments for CNS-regulated hormones were selected from the largest publicly available genome-wide association studies of the European population. Summary-level data on COVID-19 severity, hospitalization, and susceptibility were obtained from the COVID-19 host genetic initiative. DHEA was associated with increased risks of very severe respiratory syndrome (odds ratio [OR] = 4.21, 95% confidence interval [CI]: 1.41–12.59), consistent with multivariate MR results (OR = 3.72, 95% CI: 1.20–11.51), and hospitalization (OR = 2.31, 95% CI: 1.13–4.72) in univariate MR. LH was associated with very severe respiratory syndrome (OR = 0.83; 95% CI: 0.71–0.96) in univariate MR. Estrogen was negatively associated with very severe respiratory syndrome (OR = 0.09, 95% CI: 0.02–0.51), hospitalization (OR = 0.25, 95% CI: 0.08–0.78), and susceptibility (OR = 0.50, 95% CI: 0.28–0.89) in multivariate MR. We found strong evidence for the causal relationship of DHEA, LH, and estrogen with COVID-19 phenotypes. Full article

(This article belongs to the Special Issue New Advances in Clinical Genetics and Genetic Epidemiology)

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12 pages, 2853 KiB

Open AccessArticle

Does Having Rheumatoid Arthritis Increase the Dose of Depression Medications? A Mendelian Randomization Study

by Xianjie Wan, Jiale Xie, Mingyi Yang, Hui Yu, Weikun Hou, Ke Xu, Jiachen Wang and Peng Xu

J. Clin. Med. 2023, 12(4), 1405; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12041405 - 10 Feb 2023

Cited by 1 | Viewed by 1911

Abstract

Background: Rheumatoid arthritis (RA) increases the risk of depression. However, studies on the effects of RA on the dose of depression medications are limited. Therefore, in this study, we used two-sample Mendelian randomization (MR) to explore whether RA increases the dose of depression [...] Read more.

Background: Rheumatoid arthritis (RA) increases the risk of depression. However, studies on the effects of RA on the dose of depression medications are limited. Therefore, in this study, we used two-sample Mendelian randomization (MR) to explore whether RA increases the dose of depression medications and gain a more comprehensive understanding of the relationship between RA and depression. Methods: Two-sample MR was used to evaluate the causal effect of RA on the dose of depression medications. The aggregated data on RA originated from extensive genome-wide association studies (GWASs) of European descent (14,361 cases and 42,923 controls). The summary GWAS data for the dose of depression medications were derived from the FinnGen consortium (58,842 cases and 59,827 controls). Random effects inverse-variance weighted (IVW), MR-Egger regression, weighted median, and fixed effects IVW methods were used for the MR analysis. Random effects IVW was the primary method. The heterogeneity of the MR results was detected using the IVW Cochran’s Q test. The pleiotropy of the MR results was detected using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. Finally, a leave-one-out analysis was performed to determine whether the MR results were affected by a specific single-nucleotide polymorphism (SNP). Results: The primary method, random effects IVW, revealed that genetically predicted RA had a positive causal association with the dose of depression medications (Beta, 0.035; 95% confidence interval (CI), 0.007–0.064; p = 0.015). The IVW Cochran’s Q test results revealed no heterogeneity in the MR analysis (p > 0.05). The MR-Egger regression and MR-PRESSO tests revealed that there was no pleiotropy in our MR analysis. The leave-one-out analysis confirmed that a single SNP did not affect the MR results, indicating the study’s robustness. Conclusion: Using MR techniques, we discovered that having RA increases the dose of depression medications; however, the exact mechanisms and pathways still need to be further explored. Full article

(This article belongs to the Special Issue New Advances in Clinical Genetics and Genetic Epidemiology)

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9 pages, 771 KiB

Open AccessArticle

The Combined Effect of Polygenic Risk Score and Prostate Health Index in Chinese Men Undergoing Prostate Biopsy

by Xiaohao Ruan, Da Huang, Jingyi Huang, Jinlun Huang, Yongle Zhan, Yishuo Wu, Qiang Ding, Danfeng Xu, Haowen Jiang, Wei Xue and Rong Na

J. Clin. Med. 2023, 12(4), 1343; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12041343 - 8 Feb 2023

Viewed by 1587

Abstract

To date, the combined effect of polygenic risk score (PRS) and prostate health index (phi) on PCa diagnosis in men undergoing prostate biopsy has never been investigated. A total of 3166 patients who underwent initial prostate biopsy in three tertiary medical [...] Read more.

To date, the combined effect of polygenic risk score (PRS) and prostate health index (phi) on PCa diagnosis in men undergoing prostate biopsy has never been investigated. A total of 3166 patients who underwent initial prostate biopsy in three tertiary medical centers from August 2013 to March 2019 were included. PRS was calculated on the basis of the genotype of 102 reported East-Asian-specific risk variants. It was then evaluated in the univariable or multivariable logistic regression models that were internally validated using repeated 10-fold cross-validation. Discriminative performance was assessed by area under the receiver operating curve (AUC) and net reclassification improvement (NRI) index. Compared with men in the first quintile of age and family history adjusted PRS, those in the second, third, fourth, and fifth quintiles were 1.86 (odds ratio, 95% confidence interval (CI): 1.34–2.56), 2.07 (95%CI: 1.50–2.84), 3.26 (95%CI: 2.36–4.48), and 5.06 (95%CI: 3.68–6.97) times as likely to develop PCa (all p < 0.001). Adjustment for other clinical parameters yielded similar results. Among patients with prostate-specific antigen (PSA) at 2–10 ng/mL or 2–20 ng/mL, PRS still had an observable ability to differentiate PCa in the group of prostate health index (phi) at 27–36 (P_trend < 0.05) or >36 (P_trend ≤ 0.001). Notably, men with moderate phi (27–36) but highest PRS (top 20% percentile) would have a comparable risk of PCa (positive rate: 26.7% or 31.3%) than men with high phi (>36) but lowest PRS (bottom 20% percentile positive rate: 27.4% or 34.2%). The combined model of PRS, phi, and other clinical risk factors provided significantly better performance (AUC: 0.904, 95%CI: 0.887–0.921) than models without PRS. Adding PRS to clinical risk models could provide significant net benefit (NRI, from 8.6% to 27.6%), especially in those early onset patients (NRI, from 29.2% to 44.9%). PRS may provide additional predictive value over phi for PCa. The combination of PRS and phi that effectively captured both clinical and genetic PCa risk is clinically practical, even in patients with gray-zone PSA. Full article

(This article belongs to the Special Issue New Advances in Clinical Genetics and Genetic Epidemiology)

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12 pages, 2586 KiB

Open AccessArticle

Identification of S100A9 as a Potential Inflammation-Related Biomarker for Radiation-Induced Lung Injury

by Youyi Liu, Mengdi Wu, Jingrou Guo, Yifei Tang, Hongliang Jiang, Bo Yang, Minchen Wu and Jianfeng Huang

J. Clin. Med. 2023, 12(3), 733; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm12030733 - 17 Jan 2023

Cited by 1 | Viewed by 1830

Abstract

Radiation-induced lung injury (RILI), a potentially fatal and dose-limiting complication of radiotherapy for thoracic tumors, is divided into early reversible pneumonitis and irreversible advanced-stage fibrosis. Early detection and intervention contribute to improving clinical outcomes of patients. However, there is still a lack of [...] Read more.

Radiation-induced lung injury (RILI), a potentially fatal and dose-limiting complication of radiotherapy for thoracic tumors, is divided into early reversible pneumonitis and irreversible advanced-stage fibrosis. Early detection and intervention contribute to improving clinical outcomes of patients. However, there is still a lack of reliable biomarkers for early prediction and clinical diagnosis of RILI. Given the central role of inflammation in the initiation and progression of RILI, we explored specific inflammation-related biomarkers during the development of RILI in this study. Two expression profiles from the Gene Expression Omnibus (GEO) database were downloaded, in which 75 differentially expressed genes (DEGs) were screened out. Combining Gene Oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein–protein interaction (PPI) network analysis, we identified four inflammation-related hub genes in the progression of RILI—MMP9, IL-1β, CCR1 and S100A9. The expression levels of the hub genes were verified in RILI mouse models, with S100A9 showing the highest level of overexpression. The level of S100A9 in bronchoalveolar lavage fluid (BALF) and the expression of S100A9 in lung tissues were positively correlated with the degree of inflammation in RILI. The results above indicate that S100A9 is a potential biomarker for the early prediction and diagnosis of the development of RILI. Full article

(This article belongs to the Special Issue New Advances in Clinical Genetics and Genetic Epidemiology)

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12 pages, 5648 KiB

Open AccessArticle

by Tuanjie Guo, Jian Zhang, Zhihao Yuan, Heting Tang, Tao Wang, Xiang Wang and Siteng Chen

J. Clin. Med. 2022, 11(24), 7507; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11247507 - 18 Dec 2022

Viewed by 1693

Abstract

Cuproptosis is a newly discovered type of cell death. The role and potential mechanism of Cuproptosis-related genes (CRGs) in the prognosis of cancer patients are not fully understood. In this study, we included two cohorts of clear cell renal cell carcinoma patients, TCGA [...] Read more.

Cuproptosis is a newly discovered type of cell death. The role and potential mechanism of Cuproptosis-related genes (CRGs) in the prognosis of cancer patients are not fully understood. In this study, we included two cohorts of clear cell renal cell carcinoma patients, TCGA and E-MTAB-1980. The TCGA cohort is used as a training set to construct a CRG signature using the LASSO-cox regression analysis, and E-MTAB-1980 is used as a cohort for verification. A total of eight genes (FDX1, LIAS, LIPT1, DLAT, PDHA1, MTF1, GLS, CDKN2A) were screened to construct a prognostic model in the TCGA cohort. There is a significant difference in OS (p < 0.0001) between the high and low cuproptosis score group, and a similar difference is also observed in the OS (p = 0.0054) of the E-MTAB-1980 cohort. The area under the ROC curves (AUC) were 0.87, 0.82, and 0.78 at 1, 3, and 5 years in the TCGA cohort, respectively. Finally, gene set enrichment analysis revealed that CRGs were associated with cell cycle and mitotic signaling pathways. Full article

(This article belongs to the Special Issue New Advances in Clinical Genetics and Genetic Epidemiology)

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18 pages, 4844 KiB

Open AccessArticle

Comprehensive Analysis of a Novel Immune-Related Gene Signature in Lung Adenocarcinoma

by Hongxiang Feng, Chaoyang Liang, Yuhui Shi, Deruo Liu, Jin Zhang and Zhenrong Zhang

J. Clin. Med. 2022, 11(20), 6154; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11206154 - 19 Oct 2022

Viewed by 1679

Abstract

Lung cancer is the major cause of cancer-related deaths around the world. Lung adenocarcinoma (LUAD), the most common subtype of lung cancer, contributed to the majority of mortalities and showed different clinical outcomes in prognosis. Tumor-infiltrated immune cells at the tumor site are [...] Read more.

Lung cancer is the major cause of cancer-related deaths around the world. Lung adenocarcinoma (LUAD), the most common subtype of lung cancer, contributed to the majority of mortalities and showed different clinical outcomes in prognosis. Tumor-infiltrated immune cells at the tumor site are associated with better survival and immunotherapy response. Thus, it is essential to further investigate the molecular mechanisms and new prognostic biomarkers of lung adenocarcinoma development and progression. In this study, a six-gene signature (CR2, FGF5, INSL4, RAET1L, AGER, and TNFRSF13C) was established to predict the prognosis of LUAD patients, as well as predictive value. The prognostic risk model was also significantly associated with the infiltration of immune cells in LUAD microenvironments. To sum up, a novel immune-related six-gene signature (CR2, FGF5, INSL4, RAET1L, AGER, and TNFRSF13C) was identified that could predict LUAD survival and is highly related to B cells and dendritic cells, which may provide a theoretical basis of personalized treatment for targeted immunotherapy. Full article

(This article belongs to the Special Issue New Advances in Clinical Genetics and Genetic Epidemiology)

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