Tubulin alpha-1b chain was identified as a prognosis and immune biomarker in pan-cancer combing with experimental validation in breast cancer.

The α-tubulin subtype, Tubulin α-1b chain (TUBA1B), has been shown to influence immune cell infiltration, cancer growth, and survival across various malignancies. However, a comprehensive study has not yet been undertaken examining the immunological and predictive effects of TUBA1B in a pan-carcinoma context. Using data from TCGA, GEO, and other databases, we analyzed TUBA1B expression across various carcinoma types using transcriptional profiling, prognostic implications, genetic and epigenetic alterations, methylation patterns, and immunological significance. To validate our findings, we conducted Western blot analysis to assess TUBA1B protein levels in matched breast cancer tissue samples and performed CCK-8 proliferation assay, flow cytometry, transwell invasion, and migration assays to comprehensively examine the functional impact of TUBA1B on breast cancer cells. Our pan-cancer analysis found TUBA1B upregulation across most tumor types, with varying expression patterns in distinct immune and molecular subtypes. High TUBA1B expression was an independent risk factor and associated with poor prognoses in several cancers, including BRCA, KICH, LGG, LUAD, and MESO. TUBA1B also demonstrates moderate to high diagnostic accuracy in most tumor types. Increased m6A methylation levels were observed in the TUBA1B gene, while its promoter region displayed low methylation levels. TUBA1B's expression impacted some cancers by elevating tumor mutation burden, microsatellite instability, neoantigen formation, immune cell infiltration, and the modulation of immune checkpoints. Functional enrichment analysis highlights TUBA1B's involvement in important cellular processes such as the cell cycle, p53 signaling, cell senescence, programmed cell death, and the regulation of immune-related pathways. Moreover, our study reveals higher TUBA1B protein expression in breast cancer tissues compared to adjacent tissues. In vitro experiments confirm that TUBA1B deletion reduces breast cancer cell proliferation, invasion, and migration while increasing apoptosis. In conclusion, our study suggests that TUBA1B could potentially serve as a diagnostic marker for predicting cancer immunological profiles and survival outcomes and shed light on the expression and role of TUBA1B in breast cancer, providing a solid foundation for considering it as a promising therapeutic target for breast cancer patient treatment.

Cytokine-induced apoptosis inhibitor 1: a comprehensive analysis of potential diagnostic, prognosis, and immune biomarkers in invasive breast cancer.

Background: Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is strictly associated with the incidence and progress of several malignant tumors, but its effect on invasive breast cancer (IBC) remains unclear. We directed to research the potential diagnostic and prognostic significance of CIAPIN1 in IBC. Methods: The Cancer Genome Atlas (TCGA) database and Tumor Immune Estimation Resource (TIMER) database were utilized to examine CIAPIN1 expression level in IBC and its relationship with clinicopathological features. The diagnostic value and prognostic importance of CIAPIN1 in IBC were assessed by Kaplan-Meier analysis, Cox regression analysis, receiver operating characteristic (ROC) curve and nomogram model. The STRING database and enrichment analysis were utilized to discover the interacting proteins, biological roles and possible cellular mechanisms related to CIAPIN1. The methylation status of CIAPIN1 was analyzed using MethSurv database and the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN). By using Spearman correlation assessment, how the expression of CIAPIN1 was related to TP53, immune checkpoint genes and immune cell infiltration was determined. Results: CIAPIN1 mRNA and protein levels were overexpressed in IBC, and significantly correlated with T stage, histological type, age, ER status, PR status and PAM50 (P<0.001). CIAPIN1 overexpression significantly decreased overall survival, distant metastasis free survival (DMFS) and relapse free survival in IBC patients (P<0.001). Similarly, hypermethylation of CIAPIN1 was associated with adverse outcomes in IBC patients. Multivariate Cox analysis identified CIAPIN1 as a potential risk factor for disease specific survival (DSS) and progression free survival (PFS) in individuals with IBC. The outcomes of the ROC curve showed that CIAPIN1 had a better accuracy in predicting ER(-), PR(-) and Asian breast cancer subtypes. Furthermore, there was a substantial correlation between the CIAPIN1 expression level in IBC and immune cell infiltration, TP53, and immune checkpoint genes. Conclusions: The high expression of CIAPIN1 in IBC is significantly related to the infiltration status of various tumor immune cells and the poor prognosis of IBC patients. According to this current study, CIAPIN1 is a promising diagnostic and prognostic marker for IBC.

Gelsolin: A comprehensive pan-cancer analysis of potential prognosis, diagnostic, and immune biomarkers.

Introduction: Gelsolin (GSN), a calcium-regulated actin-binding protein, is out of balance in various cancers. It can mediate cytoskeletal remodeling and regulate epithelial-mesenchymal conversion (EMT), but the studies on GSN function in pan-cancer are limited. Methods: We studied the transcription level, prognostic impact, diagnostic value, genetic, epigenetic modification, methylation level and immune significance of GSN in pan-cancer to fully comprehend the function of GSN in various malignancies based on multiple databases like The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Results: Pan-cancer research showed that GSN was downregulated in most tumors and expressed differently in immunological and molecular subtypes of many cancers. GSN had varying impacts on the prognosis of various tumor types. However, all had moderate to high diagnostic efficiency, and serum GSN had good diagnostic value in breast cancer patients (AUC = 0.947). Moreover, GSN was a distinguishing prognosis factor for some specific cancer types. The GSN protein was hypophosphorylated, and its promoter was hypermethylated in most cancers. GSN was linked to the infiltration level of several immunity cells and was essential in anti-tumor immune cell infiltration. KEGG and GSEA analyses showed that GSN was vital in the functions and proteoglycans processes in cancer, chemokine signaling pathway and other immune-related pathways, DNA methylation and cell cycle. Discussion: In conclusion, GSN possesses the ability to be a predictive, diagnostic, and immune indicator in pan-cancer.

TIGIT as a Novel Prognostic Marker for Immune Infiltration in Invasive Breast Cancer.

BACKGROUND: To assess the levels and potential therapeutic and prognostic significance of TIGIT in invasive breast cancer. METHODS: The Cancer Genome Atlas database was used to evaluate TIGIT levels in invasive breast cancer and its association with clinicopathological features. Immunohistochemistry (IHC) was performed to validate it. Further, the Kaplan-Meier survival curve, univariate and multivariate Cox regression models were applied in analyzing the role of TIGIT in the prognosis of invasive breast cancer. Go / KEGG enrichment analyses techniques were used to investigate the possible cellular mechanism, and string database was used to explore TIGIT-related proteins. Finally, the TIMER database was used to determine the association between TIGIT and immune cell infiltrations. RESULTS: TIGIT was differentially expressed in Pan cancer tissues compared with normal tissues. Relative to normal tissues, TIGIT levels in invasive breast cancer were elevated (p<0.05). TIGIT mRNA level was significantly different from T stage, age, ER and PR level (p<0.05). The high levels of TIGIT exhibited positive correlations with PFI and OS (p<0.05). Univariate analysis revealed that age, clinical stage, high TNM stage, menopausal status and radiotherapy were the factors affecting OS (p< 0.05). Multivariate analysis revealed that age, high clinical stage and menopausal status were independent risk factors for tumor progression (p<0.05). CD226, INPP5D, PVR, PVRL2 and PVRL3 proteins interact with TIGIT. The TIGIT levels were significantly correlated with infiltrations of immune cells (such as CD8+ T cells) (r=0.917, p<0.05). CONCLUSION: TIGIT is elevated in invasive breast tumor and is closely associated with the prognosis of invasive breast cancer. TIGIT may be the target of immunotherapy for invasive breast cancer.

microRNA-10b expression and its correlation with molecular subtypes of early invasive ductal carcinoma.

The present study aimed to determine whether the expression of microRNA (miR)-10b was correlated with the molecular subtypes of early invasive ductal carcinoma of the breast. In situ hybridization was used to detect the expression of miR-10b in 193 patients diagnosed with early invasive ductal carcinoma. Immunohistochemistry was performed to evaluate the expression of estrogen receptor (ER)-α, progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2). The positive expression rate of miR-10b in patients with early invasive ductal carcinoma with ER-α (+) or PR (+) was decreased compared with ER-α (-) or PR (-) patients (P<0.05). Furthermore, the positive expression rate of miR-10b in patients with Her-2 (-) was significantly increased compared with patients that were Her-2 (+) (P=0.031). The positive expression rate of miR-10b in the luminal B subtype was significantly decreased compared with that in the luminal A, Her-2 and basal-like subtypes (P=0.037). In patients that were identified as miR-10b (+), the median disease-free survival time was significantly increased in patients that were ER-α (+)/PR (+)/Her-2 (-) compared with patients that were ER-α (-)/PR (-)/Her-2 (+) (P<0.05). In addition, the median disease-free survival time was significantly decreased in Her-2 overexpression and basal-like subtypes when compared with luminal A and B subtypes (P<0.05). The molecular subtype was an independent prognostic factor for early invasive ductal carcinoma (odds ratios for luminal B, Basal-like, and Her-2 overexpression were 2.900, 5.232 and 4.214, respectively; all P<0.05). Positive expression of miR-10b may also be a prognostic risk factor (odds ratio >1), though this was not statistically significant (P>0.05). The present findings indicated that miR-10b-positive expression was correlated with the expression of ER-α, Her-2 and the molecular subtypes of early invasive ductal carcinoma of the breast.

ERß overexpression results in endocrine therapy resistance and poor prognosis in postmenopausal ERα-positive breast cancer patients.

The aim of the present study was to investigate the role of estrogen receptor (ER) ß in the prognosis of ERα-positive breast cancer in postmenopausal women, and its effect on the efficacy of endocrine therapy. Tissue specimens from 195 patients with postmenopausal breast cancer were analyzed. ERß expression levels were detected using immunohistochemical staining. Kaplan-Meier analysis was performed to assess patient survival, and the difference in survival was analyzed using the log-rank test. Cox regression was utilized to evaluate prognostic factors. The results revealed that the disease-free survival rate decreased dramatically as ERß expression levels increased in all postmenopausal ERα-positive breast cancer patients, and ERß expression was identified to be an indicator of poor prognosis in cases of this disease. Similarly, in postmenopausal ERα-positive breast cancer patients undergoing endocrine therapy, high ERß expression levels reduced the disease-free survival rate and were correlated with poor patient prognosis. However, in such patients who were not treated with endocrine therapy, disease-free survival rate and prognosis were not significantly affected by ERß expression. In conclusion, ERß overexpression led to endocrine therapy resistance and poor prognosis in postmenopausal ERα-positive breast cancer patients, suggesting that ERß may affect breast cancer prognosis via an increase in endocrine therapy resistance.