Thyroid Hormone Replacement Therapy Is Associated with Longer Overall Survival in Patients with Resectable Gastroesophageal Cancer: A Retrospective Single-Center Analysis

Puhr, Hannah Christina; Reiter, Thorsten J; El-Mahrouk, Mohamed; Saliternig, Lena; Wolf, Peter; Mair, Maximilian J.; Steindl, Ariane; Paireder, Matthias; Asari, Reza; Schoppmann, Sebastian F.; Berghoff, Anna S.

doi:10.3390/cancers13205050

Cited by 2 publications

(1 citation statement)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aldosterone and relaxin pathways were concentrated in younger group, while growth hormone synthesis, secretion and action and thyroid hormone signaling pathway were concentrated in older group. Although there were many studies suggesting the relationship between these hormones and GC or other cancer, a lack of consensus existed regarding these hormones as a signi cant factor of pathogenesis mechanisms in younger female patients with GC, and further research was needed to explore their implications [32][33][34][35][36][37][38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Molecular characteristics, potential mechanisms and prognostic gene model of younger female patients with gastric cancer

Luan,

Zhao,

Wang

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Male patients were twice as likely to develop gastric cancer (GC) compared to females, partly due to the protective effect of estrogen. However, the proportion of females increased in the young GC patients. The study was designed to explore comprehensive molecular profiles of younger female GC patients, as well as develop a prognostic gene model for female GC patients. Methods Gene expression and clinical data of GC and non-tumor patients were downloaded from the Gene Expression Omnibus (GEO) database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to find molecular characteristics and potential mechanisms of younger female GC patients. The prognostic gene model containing 6 differential expressed genes (DEGs), which were between younger and older female patients, was established using Lasso-Cox regression. Its performance was validated by external validation. Then, receiver operating characteristic (ROC) curve was applied to determine the prognostic value of the prognostic gene model. Results Six GEO cohorts with 305 female GC patients (69 younger patients and 236 older patients) and 38 female non-tumor patients were included. A total of 4557 DEGs between female GC patients and non-tumor patients were identified, including 2212 up-regulated genes and 2345 down-regulated genes. Estrogen response early (p < 0.001) and estrogen response late (p < 0.001) were enriched in female GC patients. In KEGG analysis, aldosterone (p = 0.023) and relaxin pathways (p = 0.043) were concentrated in younger group. Moreover, we further used GSE84437 cohort to construct a prognostic gene model containing 6 genes, namely NREP, GAD1, SLCO4A1, KRT17, DEFB1, and P3H2, to predict the overall survival (OS) of female GC patients (AUC = 0.810). Younger female patients, who were related with high-risk at the genetic level, showed worse OS compared with older female patients who showed low-risk (HR = 5.7688, 95%CI: 3.0108–11.0530, P < 0.001). Conclusions In conclusion, we provided the comprehensive molecular profiles of younger female GC patients and found that there was a significant difference in enriched hormone-related pathways between younger group and older group. In addition, we found younger female patients showed worse OS compared with older female patients using the prognostic gene model we created.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular characteristics, potential mechanisms and prognostic gene model of younger female patients with gastric cancer

Luan,

Zhao,

Wang

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Causal relationship between thyroid dysfunction and gastric cancer: a two-sample Mendelian randomization study

Zhang,

Mu,

Jiang

et al. 2024

Front. Endocrinol.

View full text Add to dashboard Cite

BackgroudGastric cancer is one of the most common cancers worldwide, and its development is associated with a variety of factors. Previous observational studies have reported that thyroid dysfunction is associated with the development of gastric cancer. However, the exact relationship between the two is currently unclear. We used a two-sample Mendelian randomization (MR) study to reveal the causal relationship between thyroid dysfunction and gastric cancer for future clinical work.Materials and methodsThis study is based on a two-sample Mendelian randomization design, and all data are from public GWAS databases. We selected hyperthyroidism, hypothyroidism, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) as exposures, with gastric cancer as the outcome. We used three statistical methods, namely Inverse-variance weighted (IVW), MR-Egger, and weighted median, to assess the causal relationship between thyroid dysfunction and gastric cancer. The Cochran’s Q test was used to assess the heterogeneity among SNPs in the IVW analysis results, and MR-PRESSO was employed to identify and remove IVs with heterogeneity from the analysis results. MR-Egger is a weighted linear regression model, and the magnitude of its intercept can be used to assess the horizontal pleiotropy among IVs. Finally, the data were visualized through the leave-one-out sensitivity test to evaluate the influence of individual SNPs on the overall causal effect. Funnel plots were used to assess the symmetry of the selected SNPs, forest plots were used to evaluate the confidence and heterogeneity of the incidental estimates, and scatter plots were used to assess the exposure-outcome relationship. All results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). P<0.05 represents statistical significance.ResultsAccording to IVW analysis, there was a causal relationship between hypothyroidism and gastric cancer, and hypothyroidism could reduce the risk of gastric cancer (OR=0.936 (95% CI:0.893-0.980), P=0.006).This means that having hypothyroidism is a protective factor against stomach cancer. This finding suggests that hypothyroidism may be associated with a reduced risk of gastric cancer.Meanwhile, there was no causal relationship between hyperthyroidism, FT4, and TSH and gastric cancer.ConclusionsIn this study, we found a causal relationship between hypothyroidism and gastric cancer with the help of a two-sample Mendelian randomisation study, and hypothyroidism may be associated with a reduced risk of gastric cancer, however, the exact mechanism is still unclear. This finding provides a new idea for the study of the etiology and pathogenesis of gastric cancer, and our results need to be further confirmed by more basic experiments in the future.

show abstract

Thyroid Hormone Replacement Therapy Is Associated with Longer Overall Survival in Patients with Resectable Gastroesophageal Cancer: A Retrospective Single-Center Analysis

Cited by 2 publications

References 40 publications

Molecular characteristics, potential mechanisms and prognostic gene model of younger female patients with gastric cancer

Molecular characteristics, potential mechanisms and prognostic gene model of younger female patients with gastric cancer

Causal relationship between thyroid dysfunction and gastric cancer: a two-sample Mendelian randomization study

Contact Info

Product

Resources

About