Utility of vitamin D serum evaluation and supplementation in dogs and cats’ medical routine: a review

Vitamin D is traditionally known for its role in regulating calcium homeostasis and consequently maintaining bone integrity and health. However, more recently, it has been observed that it has a series of previously unknown non-canonical functions, such as maintenance of immunity and intestinal mucosa integrity. Furthermore, it has been shown to be associated with the progression or perpetuation of several diseases since its serum concentration is reduced during the course of the conditions. Therefore, we sought to investigate, through a literature review, the usefulness of serum vitamin D measurement in dogs and cats as a prognostic factor for different diseases, as well as the possible therapeutic effect of supplementing this vitamin in the correction of those illnesses. Vitamin D is in fact deficient in gastroenteric diseases, such as protein-losing enteropathy, infectious diseases, such as canine leishmaniasis, heart and kidney disease, among others. However, it is necessary to understand more properly about the physiological role of vitamin D in health, so that we can also understand it in disease. There are also too few data reports supporting supplementing this vitamin as main or adjuvant therapy in the treatment of any disease, but evidence points to the usefulness of vitamin D serum measurement as a prognostic predictor for dogs and cats.

Prognostic Efficacy of Tumor-Stroma Ratio in Women With Breast Cancer: A Meta-Analysis of Cohort Studies

BackgroundTumor-stroma ratio (TSR) has been suggested as an emerging prognostic predictor in women with breast cancer. However, previous studies evaluating the association between TSR and survival in women with breast cancer showed inconsistent results. We performed a meta-analysis to systematically evaluate the possible prognostic role of TSR in breast cancer.MethodsRelevant cohort studies were obtained via search of PubMed, Embase, and Web of Science databases. A random-effects model, which incorporated the potential heterogeneity, was used to pool the results.ResultsTwelve cohort studies with 6175 patients were included. Nine of the 12 studies used 50% as the cutoff to divide the patients into those with stroma-rich (low TSR) and stroma-poor (high TSR) tumors. Pooled results showed that compared women with stroma-poor tumor, those with stroma-rich tumor were associated with worse survival outcomes (disease-free survival [DFS]: hazard ratio [HR] = 1.56, 95% confidence interval [CI]: 1.32 to 1.85, P < 0.001; overall survival [OS]: HR = 1.67, 95% CI: 1.46 to 1.91, P < 0.001; and cancer-specific survival [CSS]: HR = 1.75, 95% CI: 1.40 to 2.20, P < 0.001). Analysis limited to women with triple-negative breast cancer (TNBC) showed consistent results (DFS: HR: 2.07, 95% CI: 1.59 to 2.71, P < 0.001; OS: HR: 2.04, 95% CI: 1.52 to 2.73, P < 0.001; and CSS: HR: 2.40, 95% CI: 1.52 to 3.78, P < 0.001).ConclusionsCurrent evidence from retrospective studies supports that tumor TSR is a prognostic predictor or poor survival in women with breast cancer.

Multi-omics analysis of an immune-based prognostic predictor in non-small cell lung cancer

Background Inhibitors targeting immune checkpoints, such as PD-1/PD-L1 and CTLA-4, have prolonged survival in small groups of non-small cell lung cancer (NSCLC) patients, but biomarkers predictive of the response to the immune checkpoint inhibitors (ICIs) remain rare. Methods The nonnegative matrix factorization (NMF) was performed for TCGA-NSCLC tumor samples based on the LM22 immune signature to construct subgroups. Characterization of NMF subgroups involved the single sample gene set variation analysis (ssGSVA), and mutation/copy number alteration and methylation analyses. Construction of RNA interaction network was based on the identification of differentially expressed RNAs (DERs). The prognostic predictor was constructed by a LASSO-Cox regression model. Four GEO datasets were used for the validation analysis. Results Four immune based NMF subgroups among NSCLC patients were identified. Genetic and epigenetic analyses between subgroups revealed an important role of somatic copy number alterations in determining the immune checkpoint expression on specific immune cells. Seven hub genes were recognized in the regulatory network closely related to the immune phenotype, and a three-gene prognosis predictor was constructed. Conclusions Our study established an immune-based prognosis predictor, which might have the potential to select subgroups benefiting from the ICI treatment, for NSCLC patients using publicly available databases.

Bioinformatic Analyses and Experimental Verification Reveal that High FSTL3 Expression Promotes EMT via Fibronectin-1/α5β1 Interaction in Colorectal Cancer

Background: Colorectal cancer (CRC) is a typical cancer prevalent worldwide. Despite the conventional treatments, CRC has a poor prognosis due to relapse and metastasis. Moreover, there is a dearth of sensitive biomarkers for predicting prognosis in CRC.Methods: This study used a bioinformatics approach combining validation experiments to examine the value of follistatin-like 3 (FSTL3) as a prognostic predictor and therapeutic target in CRC.Results:FSTL3 was remarkably upregulated in the CRC samples. FSTL3 overexpression was significantly associated with a poor prognosis. FSTL3 was found to activate the epithelial-mesenchymal transition by promoting the binding of FN1 to α5β1. FSTL3 expression was also positively correlated with the abundance of the potent immunosuppressors, M2 macrophages.Conclusion:FSTL3 overexpression affects CRC prognosis and thus, FSTL3 can be a prognostic biomarker and therapeutic target with potential applications in CRC.

Comprehensive Analysis Uncovers Prognostic and Immunogenic Characteristics of Cellular Senescence for Lung Adenocarcinoma

Cellular senescence plays a crucial role in tumorigenesis, development and immune modulation in cancers. However, to date, a robust and reliable cellular senescence-related signature and its value in clinical outcomes and immunotherapy response remain unexplored in lung adenocarcinoma (LUAD) patients. Through exploring the expression profiles of 278 cellular senescence-related genes in 936 LUAD patients, a cellular senescence-related signature (SRS) was constructed and validated as an independent prognostic predictor for LUAD patients. Notably, patients with high SRS scores exhibited upregulation of senescence-associated secretory phenotype (SASP) and an immunosuppressive phenotype. Further analysis showed that SRS combined with immune checkpoint expression or TMB served as a good predictor for patients’ clinical outcomes, and patients with low SRS scores might benefit from immunotherapy. Collectively, our findings demonstrated that SRS involved in the regulation of the tumor immune microenvironment through SASP was a robust biomarker for the immunotherapeutic response and prognosis in LUAD.