Background/Objectives: Endometrial cancer (EC) is a multifactorial disease influenced by metabolic, hormonal, and environmental factors. Trace and macroelements play a critical role in cellular homeostasis, oxidative stress, and tumor progression; however, their relationship with EC grading and clinical characteristics remains insufficiently understood. Methods: This study evaluated the concentrations of selected macro- and trace elements (Na, K, Ca, P, Mg, Mn, Cu, Zn, Be, As, Cr, Mo, Ti, Tl, Pb) in patients with endometrial cancer (G1–G3) and a control group (C). Elemental analysis was performed using inductively coupled plasma optical emission spectrometry (ICP-OES). Associations between elemental concentrations and clinicopathological variables, including age, body mass index (BMI), menopausal status, diabetes, and smoking, were assessed using appropriate statistical tests, including ANOVA with Tukey’s post hoc analysis and Student’s t-test. Multivariate regression analysis was performed to identify independent predictors of elemental alterations. Results: Significant differences in elemental concentrations were observed across EC grading. Higher-grade tumors were associated with increased levels of Ca, P, Mg, and Mn, while Na and K showed a decreasing trend with tumor progression. No statistically significant differences were observed for Zn, Ti, Tl, or Pb across histological grades. Stratified analyses demonstrated that clinical and metabolic factors had a limited and selective impact on elemental profiles. Age and BMI were associated with minor variations in selected elements, whereas menopausal status, diabetes, and smoking showed predominantly non-significant or inconsistent effects. Multivariate analysis identified histological grade as the primary determinant of elemental alterations, while other variables exhibited weaker or element-specific associations. Conclusions: Elemental homeostasis in endometrial cancer is primarily associated with tumor progression rather than systemic metabolic or lifestyle factors. Changes in Ca-, P-, Mg-, and Mn-related pathways may reflect tumor-driven metabolic reprogramming, whereas most trace elements remain relatively stable. These findings suggest that elemental profiling may provide insight into EC biology, although its clinical utility requires further investigation.

Apoptosis maintains tissue homeostasis, and its dysregulation is closely associated with breast cancer progression and therapeutic resistance. We performed an integrative analysis of apoptosis-related signaling in breast cancer tissues across five molecular subtypes and compared these patterns with systemic apoptotic responses following cryoablation of benign fibroadenomas. Gene expression profiling was conducted using mRNA microarrays and validated by qRT-PCR and ELISA. Apoptosis pathway activity was assessed with the MSigDB HALLMARK_APOPTOSIS gene set, including intrinsic and extrinsic pathway scoring and an apoptotic balance index (ABI). MicroRNA profiling combined with in silico analyses identified potential miRNA–mRNA interactions. A progressive shift toward reduced pro-apoptotic and enhanced stress-adaptive signaling was observed with increasing tumor aggressiveness, most pronounced in triple-negative and non-luminal HER2-positive cancers. This pattern included reduced intrinsic pathway activity, decreased ABI, downregulation of pro-apoptotic genes (BIK, BMF, TXNIP), and upregulation of stress-associated or cytoprotective genes (HSPB1, PPT1). Several expression patterns were accompanied by overexpression of miRNAs (miR-582-5p, miR-421, miR-106b-5p, miR-20a-5p, miR-20b-5p, miR-93-5p) predicted to target apoptosis-related genes. In contrast, fibroadenoma cryoablation was associated with transient systemic modulation of apoptosis-related genes and proteins followed by gradual normalization. These findings highlight differences between apoptosis-related dysregulation in malignant tissue and regulated systemic responses following benign tissue injury, supporting pathway-level interpretation and identifying candidate molecular networks warranting further mechanistic and translational investigation.

Breast cancer (BC) comprises heterogeneous subtypes with distinct molecular drivers and clinical behaviors. Among the key signaling pathways implicated in BC progression is the mitogen-activated protein kinase (MAPK) cascade, which regulates cell proliferation, apoptosis, and stress responses. microRNAs (miRNAs), as post-transcriptional regulators, are increasingly recognized as modulators of MAPK-associated genes, yet their integrated role across BC subtypes remains incompletely understood. This study included 405 patients with histopathologically confirmed BC, stratified into luminal A (LumA), HER2-negative luminal B, HER2-positive luminal B, non-luminal HER2-positive, and triple-negative breast cancer (TNBC). Control tissues were obtained from matched surgical margins. We performed mRNA profiling (Affymetrix microarrays), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), protein quantification (enzyme-linked immunosorbent assay (ELISA), and miRNA expression analysis. Predicted miRNA-mRNA interactions were analyzed using the miRDB database. Functional protein–protein interactions were explored using the STRING database. MAP3K1, MAP2K4, and TP53 were significantly downregulated across all subtypes, while PPM1D, LMTK3, and TGFB1 were upregulated, especially in TNBC. These alterations were supported by concordant changes at the protein level. Dysregulated miRNAs—miR-21-3p, miR-23c, miR-27a-3p, miR-205-3p, and miR-300—exhibited in-verse expression patterns relative to their predicted target genes. STRING analysis identified TP53 as a central hub, linking MAPK signaling with stress and apoptotic pathways. This integrated transcriptomic and miRNA profiling study reveals subtype-specific dysregulation of MAPK-associated genes and their miRNA regulators in BC, with TNBC exhibiting the most profound alterations. These findings provide insight into potential targets for personalized therapeutic strategies.

Colorectal cancer (CRC) is one of the most prevalent types of cancers, whose etiology has been highly related to diet. High intake of dietary fiber has been found to favor the reduction of CRC risk, as deduced from a lot of studies. The aim of this review is to explore the role of fiber in CRC chemoprevention and to provide insight into the mechanisms underlying the reduced risk of this neoplasia associated with the consumption of fiber. In this work, the authors describe the state of the literature regarding the association between intake and CRC risk through presenting data from epidemiological investigations, clinical intervention studies, and molecular mechanisms. Data were assembled from studies like the European Prospective Investigation into Cancer and Nutrition (EPIC) and fiber supplementation studies to assess the role of dietary fiber on CRC. The analysis indicated that dietary fiber intake, particularly from fruit, vegetable, and whole grain sources, is inversely related to CRC risk. Most studies, such as meta-analyses and large cohort studies, presented the significantly reduced CRC incidence of the highest intake of fiber. The favorable benefits of fiber are attributed to various modes of mechanisms, including the modulation of gut microbiota, bile acid metabolism, and a reduction in oxidative stress. Dietary fiber might play a vital role in this regard and lower the risk of CRC through its effects on different biological pathways. Promotion of dietary fiber intake could be a key strategy for the prevention of CRC, especially via a balanced diet rich in fruits, vegetables, and whole grains. Public health initiatives that aim at increasing fiber intake should start early in life to prevent not only metabolic but also neoplastic diseases more influenced by dietary factors. However, fiber supplementation appears promising, although further large-scale studies will be required to establish its definite role in CRC chemoprevention.

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation and oxidative stress, increasingly implicated in cancer biology. However, its molecular regulation across breast cancer subtypes and its potential systemic manifestations remain incompletely understood. The aim of this study was to identify ferroptosis-associated molecular alterations that are largely shared across subtypes and to evaluate their systemic reflection following localized tissue injury. Tumor and matched normal breast tissues representing major molecular subtypes were analyzed. Global mRNA and miRNA expression profiling was performed using microarrays, followed by validation of selected genes using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Functional enrichment and protein–protein interaction analyses were conducted to characterize associated pathways. In addition, systemic responses were assessed in patients undergoing fibroadenoma cryoablation through longitudinal blood sampling. Six ferroptosis-related genes (SLC7A11, GPX4, FTH1, NQO1, NFE2L2, SQSTM1) demonstrated consistent upregulation across all breast cancer subtypes, with higher expression observed in more aggressive tumors. These genes are functionally linked to antioxidant defense, iron metabolism, and oxidative stress regulation, and their coordinated expression pattern is consistent with activation of NRF2-dependent cytoprotective pathways. Downregulation of selected miRNAs may contribute to this expression profile but likely represents a secondary regulatory mechanism. Survival analysis revealed heterogeneous and subtype-dependent associations, with limited and gene-specific prognostic relevance. Cryoablation induced transient increases in circulating levels of the analyzed proteins, reflecting systemic responses to localized tissue injury. In conclusion, breast cancer is characterized by a largely shared ferroptosis-associated molecular signature across subtypes; however, its clinical impact appears to be variable and context-dependent. Systemic detection of related molecular signals suggests potential utility as indicators of tissue stress responses, although their role as specific biomarkers of ferroptosis requires further validation.

Background/Objectives: The Notch signaling pathway regulates cell fate, proliferation, and differentiation, and its dysregulation has been implicated in various cancers, including breast cancer. MicroRNAs (miRNAs) are critical post-transcriptional regulators that can modulate Notch pathway components. The aim of this study was to identify miRNAs that may potentially regulate the expression of Notch pathway-related genes across five molecular subtypes of breast cancer in Polish women. Methods: Tumor and adjacent normal tissue samples were collected from 405 patients with five breast cancer subtypes: luminal A (n = 130), HER2-negative luminal B (n = 100), HER2-positive luminal B (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (n = 43). Gene expression was profiled using mRNA microarrays and validated with RT-qPCR and ELISA. Candidate regulatory miRNAs were identified by miRNA microarrays and confirmed using the miRDB database. Results: APH1A, CTBP1, DTX1, HEY1, HEY2, JAG2, NOTCH4, TLE2, and TLE4 were consistently dysregulated across all breast cancer subtypes. Overexpression of HEY1 and JAG2 may be driven by decreased levels of miR-145, miR-98, and miR-381. Conversely, downregulation of TLE4 may be associated with elevated expression of miR-196a and miR-155. No regulatory miRNAs meeting the selection criteria were identified for APH1A, CTBP1, DTX1, HEY2, NOTCH4, or TLE2. Conclusions: The consistent alterations suggest the presence of a shared Notch-driven oncogenic signature in breast cancer, potentially driving cell proliferation, stemness, and resistance to therapy. These findings enhance our understanding of Notch signaling in breast cancer and propose novel miRNA–Notch interactions as candidate targets for therapeutic intervention.