Gastric cancer (GC) remains a significant contributor to cancer-related mortality. Novel high-throughput techniques have enlightened the epigenetic mechanisms governing gene-expression regulation. Epigenetic characteristics contribute to molecular taxonomy and give rise to cancer-specific epigenetic patterns. Helicobacter pylori (Hp) infection has an impact on aberrant DNA methylation either through its pathogenic CagA protein or by inducing chronic inflammation. The hypomethylation of specific repetitive elements generates an epigenetic field effect early in tumorigenesis. Epstein–Barr virus (EBV) infection triggers DNA methylation by dysregulating DNA methyltransferases (DNMT) enzyme activity, while persistent Hp-EBV co-infection leads to aggressive tumor behavior. Distinct histone modifications are also responsible for oncogene upregulation and tumor-suppressor gene silencing in gastric carcinomas. While histone methylation and acetylation processes have been extensively studied, other less prevalent alterations contribute to the development and migration of gastric cancer via a complex network of interactions. Enzymes, such as Nicotinamide N-methyltransferase (NNMT), which is involved in tumor’s metabolic reprogramming, interact with methyltransferases and modify gene expression. Non-coding RNA molecules, including long non-coding RNAs, circular RNAs, and miRNAs serve as epigenetic regulators contributing to GC development, metastasis, poor outcomes and therapy resistance. Serum RNA molecules hold the potential to serve as non-invasive biomarkers for diagnostic, prognostic or therapeutic applications. Gastric fluids represent a valuable source to identify potential biomarkers with diagnostic use in terms of liquid biopsy. Ongoing clinical trials are currently evaluating the efficacy of next-generation epigenetic drugs, displaying promising outcomes. Various approaches including multiple miRNA inhibitors or targeted nanoparticles carrying epigenetic drugs are being designed to enhance existing treatment efficacy and overcome treatment resistance.

Breast cancer ranks first in incidence and second in deaths worldwide, presenting alarmingly rising mortality rates. Imaging methodologies and/or invasive biopsies are routinely used for screening and detection, although not always with high sensitivity/specificity. MicroRNAs (miRNAs) could serve as diagnostic and prognostic biomarkers for breast cancer. We have designed a computational approach combining transcriptome profiling, survival analyses, and diagnostic power calculations from 1165 patients with breast invasive carcinoma from The Cancer Genome Atlas (TCGA-BRCA). Our strategy yielded two separate miRNA signatures consisting of four up-regulated and five down-regulated miRNAs in breast tumors, with cumulative diagnostic strength of AUC 0.93 and 0.92, respectively. We provide direct evidence regarding the breast cancer-specific expression of both signatures through a multicancer comparison of >7000 biopsies representing 19 solid cancer types, challenging their diagnostic potency beyond any of the current diagnostic methods. Our signatures are functionally implicated in cancer-related processes with statistically significant effects on overall survival and lymph-node invasion in breast cancer patients, which underlie their strong prognostic implication. Collectively, we propose two novel miRNA signatures with significantly elevated diagnostic and prognostic power as a functionally resolved tool for binary and accurate detection of breast cancer and other tumors of the female reproductive system.

Linitis Plastica (LP) is a rare and aggressive tumor with a distinctive development pattern, leading to the infiltration of the gastric wall, the thickening of the gastric folds and a “leather bottle appearance”. LP is an extremely heterogeneous tumor caused by mutations in oncogenic and tumor suppressive genes, as well as molecular pathways, along with mutations in stromal cells and proteins related to tight junctions. Elucidating the molecular background of tumorigenesis and clarifying the correlation between cancerous cells and stromal cells are crucial steps toward discovering novel diagnostic methods, biomarkers and therapeutic targets/agents. Surgery plays a pivotal role in LP management, serving both as a palliative and curative procedure. In this comprehensive review, we aim to present all recent data on the molecular background of LP and the novel approaches to its management.

Bladder carcinoma is globally among the most prevalent cancers and is associated with a high mortality rate at advanced stages. Its detection relies on invasive diagnostic methods that are unpleasant for the patient. Non-invasive molecular biomarkers, such as miRNAs, could serve as alternatives for early detection and prognosis of this malignancy. We designed a computational approach that combines transcriptome profiling, survival analyses, and calculation of diagnostic power in order to isolate miRNA signatures with high diagnostic and prognostic utility. Our analysis of TCGA-BLCA data from 429 patients yielded one miRNA signature, consisting of five upregulated and three downregulated miRNAs with cumulative diagnostic power that outperforms current diagnostic methods. The same miRNAs have a strong prognostic significance since their expression is associated with the overall survival of bladder cancer patients. We evaluated the expression of this signature in 19 solid cancer types, supporting its unique diagnostic utility for bladder carcinoma. We provide computational evidence regarding the functional implications of this miRNA signature in cell cycle regulation, demonstrating its abundance in body fluids, including peripheral blood and urine. Our study characterized a novel miRNA signature with the potential to serve as a non-invasive method for bladder cancer diagnosis and prognosis.

Background/Objectives: Testicular germ cell tumors (TGCT) are common in young adult men and have high cure rates. Conventional serum tumor markers and imaging are not able to differentiate between histologic subtypes of the disease, which portend different prognoses and require distinct therapeutic strategies. Micro-RNAs (miRNAs) are small non-coding transcripts involved in the post-transcriptional regulation of gene expression, which have emerged as promising biomarkers in a variety of tumors. This study aimed to assess the potential of differentially expressed miRNAs in differential diagnosis and prognostication among TGCT patients with various histologic subtypes. Methods: Transcriptomic analysis of 134 patients from The Cancer Genome Atlas (TCGA)-TGCT database was conducted. miRNA differential expression analysis among seminomatous, embryonal carcinoma, mixed GCT, and teratoma was performed, followed by ROC curve analysis of the most significantly up- and downregulated miRNAs, respectively. Statistical associations of miRNA expression with AJCC stage were also investigated along with miRNA target network analysis and evaluation of miRNA detection in patients’ fluids. Results: Upregulation of seven miRNAs (hsa-mir-135a-1, hsa-mir-135a-2, hsa-mir-200a, hsa-mir-200b, hsa-mir-203b, hsa-mir-375, hsa-mir-582) and downregulation of seven additional miRNAs (hsa-mir-105-1, hsa-mir-105-2, hsa-mir-4433a, hsa-mir-548x, hsa-mir-5708, hsa-mir-6715a, hsa-mir-767) were identified. miRNAs displayed a high sensitivity/specificity of 0.94/1.0 (AUC = 0.98) for the upregulated and 0.97/0.94 (AUC = 0.96) for the downregulated signature. Deregulated expression of these miRNAs was significantly associated with AJCC stage and distant organ metastasis (p < 0.001), overall supporting their prognostic strength. Both signatures were detectable in body fluids, particularly urine. miRNA target network analysis supported the functional role of these miRNAs in the regulation of cancer-related processes such as cell proliferation via deregulation of pivotal oncogenes. Conclusions: These findings support the clinical value of two novel miRNA signatures in differential diagnosis and prognostic stratification of various histologic subtypes of TGCT, with potential treatment implications.