Cisplatin is a widely used antineoplastic agent whose therapeutic efficacy is often limited by its adverse effects on the central nervous system. In this exploratory study, we characterized the transcriptomic impact of a cumulative cisplatin regimen on the male Wistar rat brain using microarray technology. Differentially expressed genes were identified, and their functional roles were investigated through enrichment analyses (KEGG) and Gene Ontology (GO), and the construction of protein-protein interaction (PPI) networks. Our results revealed significant alterations in pathways related to synaptic signaling, neuroplasticity, and cellular metabolism. To generate translational hypotheses, these findings were subsequently correlated in silico with public human lower-grade glioma (LGG) datasets, which suggested a potential association between key cisplatin-regulated genes and clinical prognosis and immune cell infiltration patterns. This manuscript does not include RT-qPCR (or Western blot) validation; results should be interpreted as hypothesis-generating and require orthogonal confirmation. These findings provide a comprehensive transcriptomic map of cisplatin-induced neurotoxicity, offering novel insights into its underlying molecular mechanisms and identifying a rich set of candidate targets for future neuroprotective strategies.

Non-small cell lung cancer (NSCLC) is a severe disease with a very poor prognosis. Some 30-80% of patients with NSCLC die within five years of cancer diagnosis. The main factors contributing to this condition are the lack of effective markers for diagnosing cancer at an early stage, as well as the complexity of the biological processes involved in tumorigenesis and progression. The development of knowledge regarding all aspects of NSCLC has provided information used in the detection, systemic anticancer therapy and monitoring of NSCLC, which has a significant impact on prognosis and quality of life. NSCLCs release various biological substances into the bloodstream. Liquid biopsies allow for the analysis of tumor components in body fluids, and the usefulness of these biopsy tests as a substitute for tumor tissue is increasing. In this article, we critically review the available literature on microRNAs, circulating cell-free DNA (cfDNA), tumor-educated platelets (TEPs), circulating tumor cells (CTCs), circulating extracellular vesicles (EVs), and metabolomic and proteomic markers in the diagnosis and monitoring of NSCLC. However, the usefulness of these new markers in clinical practice has significant limitations.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. In Mexico, its higher incidence and lower survival suggest a role for epigenetic factors like DNA methylation (DNAme). We conducted an epigenome-wide association study (EWAS) to define the methylation landscape and identify the profiles associated with ALL and relapse. Bone marrow or peripheral blood samples from pediatric ALL patients at diagnosis and controls without ALL were analyzed using an Infinium MethylationEPIC v2.0 array. Differential methylation was assessed using the ChAMP package. We identified a significant hypermethylated profile in ALL patients compared to controls. Probes in MAD1L1 and RPTOR contained the most differentially methylated CpG sites. Key affected pathways included proliferation, neurotransmission, and neuronal signaling. Survival analysis revealed that hypomethylation of four specific CpGs-cg01052776 (RNH1), cg20747787, cg05001671, and cg01767116 (FBXL22)-was significantly associated with an increased risk of relapse, highlighting their potential as prognostic biomarkers. This study underscores the importance of epigenetic mechanisms in pediatric ALL.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options, prompting extensive research into novel therapeutics. This study presents a comprehensive molecular characterization of usnic acid in TNBC using transcriptomic, proteomic, and in vivo analyses.

Despite a specific histone mutation defining the unique genetic makeup, diffuse midline gliomas are heterogeneous tumors with a wide range of morphologic and molecular spectrum. We investigated the feasibility of using hyperpolarized carbon-13(13C) MR metabolic imaging to differentiate distinctive molecular features from two H3K27M-mutant, biopsy-originated diffuse midline glioma xenografts. 13C MR metabolic imaging data were acquired on a 3T scanner from 12 rats that had been implanted with SF8628 or SF7761 diffuse midline glioma cells in brainstem, following injection of hyperpolarized [1-13C]pyruvate. Despite the two tumors' similar appearance of T2-hyperintensity throughout the cerebellum and pons without contrast enhancement, 13C metabolic imaging data revealed that SF8627 had significantly higher ratios of lactate to pyruvate, lactate to total carbon, and normalized lactate than SF7761. Elevated lactate levels in SF8628 were associated with large amounts of lactate dehydrogenase (LDH)-A and carbonic anhydrase-IX staining in SF8628 compared to SF7761, which implied that the highly hypoxic condition in SF8628 appeared to contribute to the high level of LDH-A enzyme activity, which, in turn, induced the large conversion from hyperpolarized pyruvate to lactate. Our findings suggest that this advanced metabolic imaging technique may be used for the noninvasive characterization of molecular hypoxia and lactate dehydrogenase-A activity in these pediatric brainstem gliomas.

Many cutaneous adnexal tumors share molecular alterations with other homologous neoplasms occurring in salivary glands. Polymorphous adenocarcinoma (PAC) is a rare salivary gland tumor, usually associated with alterations in the PRKD gene family. In this report, we describe a primary cutaneous sweat gland adenocarcinoma of the scalp occurring in a 65-year-old female. Morphological features of the carcinoma were reminiscent of salivary gland PAC. Tumor cells were CK7+ S100+ SOX10+ p63 focally positive and p40-. Whole-transcriptome sequencing of the lesion showed the presence of an in-frame ATL2::PRKD3 fusion. PRKD1, 2 or 3 fusions are characteristic of the cribriform subtype of PAC (cribriform adenocarcinoma of salivary gland, CASG). No past history of salivary gland tumor nor existing salivary gland tumor was retrieved in the patient. After complete excision of the tumor, the patient has been in complete remission for 17 months. This case suggests that a subset of adnexal adenocarcinomas of not otherwise specified type (NOS) may carry PRKD alteration and may constitute the cutaneous counterpart of salivary gland PAC/CASG. This finding argues in favor of a more systematic molecular exploration of adnexal adenocarcinomas NOS for better classification and prognosis.

There is a need to improve the translation of gastric cancer molecular classification schemes, such as those proposed by the Cancer Genome Atlas (TCGA) and Tumour Microenvironment score (TME), to clinical specimens and three-dimensional organoid culture models. In this study, we validate a 107-gene Nanostring assay informed by previously established machine learning models using a prospective cohort of gastric adenocarcinoma tumours and tumour-organoid pairs. Thirty-eight gastric adenocarcinoma specimens and twelve parent tumour-tumour organoid pairs were assigned TCGA and TME subtypes using gene expression measured by our custom Nanostring gene set. Subtypes were validated using gold-standard tests for Epstein-Barr virus (EBV) and microsatellite instability (MSI). Molecular subtype scores were compared to known clinicopathologic characteristics. The correlation between dose-response and molecular subtypes using an organoid drug assay and the Cancer Cell Line Encyclopedia (CCLE) was investigated. TCGA and TME subtypes were successfully applied to all specimens. The relationship of molecular subtype scores in our population compared to public cohorts was statistically identical for Lauren Class and Signet Ring status. Our method achieved 100% accuracy in labeling EBV and MSI subtypes. We identified 81.8% and 63.6% concordance between parent tumour-tumour organoid pairs for TME and TCGA subtypes, respectively. No significant correlation was identified between dose response to chemotherapy and molecular subtype scores. Analysis of the CCLE identified promising personalized therapy candidates for each molecular subtype. Our 107-gene Nanostring test successfully assigns TCGA and TME molecular subtypes to clinical tumour and tumour organoid samples for use in future study.

Ossifying fibromyxoid tumor (OFMT) is an extremely rare mesenchymal tumor of uncertain differentiation having a potential for local recurrences and metastasis. OFMT can be classified as typical, atypical, and malignant tumors based on nuclear grade, cellularity, and mitotic rate. However, predicting the biological behavior remains challenging. We report one of these challenging cases of OFMT with metastases after 19 years. The primary tumor did not show morphologic characteristics of malignancy. We performed targeted RNA sequencing, copy number variation (CNV) analysis on all lesions and additional DNA methylation profiling.

Gastric cancer (GC) ranks as the third leading reason of cancer-associated deaths worldwide. This study investigates the mechanism by which the m6A methyltransferase methyltransferase-like 14 (METTL14) enhances ferroptosis and inhibits GC progression through regulation of sirtuin 5 (SIRT5).

Tumor cell differentiation is a critical determinant of malignancy and clinical treatment selection. Pancreatic ductal adenocarcinoma (PDAC), a poorly differentiated and highly aggressive tumor, has a poor prognosis, whereas well-differentiated tumors often correlate with better outcomes. The mechanisms underlying differentiation and its therapeutic potential remain unclear.

The genetic heterogeneity observed in acute myeloid leukemia (AML) contributes to a wide range of clinical presentations and prognoses. We conducted a retrospective study to investigate genetic abnormalities, clinical characteristics, and survival of AML patients.

Although anticancer therapies inducing necrosis, necroptosis and pyroptosis trigger cell swelling, plasma membrane rupture (PMR) and release of damage-associated molecular patterns (DAMPs), potentially facilitating antitumor immunity, little was known of proteins and mechanisms controlling the life-death decision of whether swollen and stressed cancer cells enter PMR and undergo lytic cell death.

DNA methylation profiling has emerged as a promising tool for improving pathological diagnosis. This study investigates the diagnostic efficacy and subgroup heterogeneity of SHOX2, RASSF1A, Septin9, and HOXA9 methylation in pleural effusion lymphoma, aiming to enhance diagnostic accuracy and identify high-risk molecular subgroups.

Patients with BRAF V600E-mutated/microsatellite stable (MSS) metastatic colorectal cancer (mCRC) are associated with a poor prognosis. Backline treatment has minimal efficacy. Multi-target inhibitors of the RAS-RAF-MEK signaling pathway combined with PD-1 monoclonal antibody may be a promising strategy for BRAF V600E-mutated mCRC.

Interleukin-1 receptor accessory protein (IL1RAP) is selectively expressed on both bulk blasts and leukemic stem cells (LSCs) in acute myeloid leukemia (AML), while its expression is virtually absent on normal hematopoietic stem cells (HSCs), making it an appealing target for chimeric antigen receptor (CAR) T cell therapy.

For HER2-positive breast cancer (BC), patients who achieve pathologic complete response (pCR) are predicted to have better clinical outcomes. With the advent of the era of neoadjuvant chemotherapy (NAC) combined with targeted therapy, the pCR rate of HER2-positive BC has increased significantly, but about 50% of these patients still do not respond to targeted therapy. The dynamic changes in the tumor microenvironment (TME) may crucially influence pCR outcomes in HER2-positive BC. However, there is no specific immunophenotyping study that correlates with the efficacy during treatment.

Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer, characterized by high mortality rates. KAT2A has been implicated in oncogenic processes and tumor progression. This study systematically investigated the role of KAT2A in LUAD through comprehensive analyses. Expression profiles and prognostic significance of KAT2A were evaluated using TCGA database and multiple GEO datasets. Functional enrichment analyses including GO and KEGG pathway analyses were conducted to elucidate biological mechanisms associated with KAT2A-regulated differentially expressed genes. Correlations between KAT2A expression levels and immune cell infiltration were analyzed using R software and publicly available databases. Experimental validation was performed through CCK-8 assays, colony formation assays, flow cytometry, and xenograft tumor models. Our findings demonstrated significantly elevated KAT2A expression in LUAD tissues and cells. Expression levels correlated with multiple clinicopathological parameters including TNM stage, pathological stage, sex, and tumor localization. High KAT2A expression was associated with reduced overall survival and exhibited prognostic relevance across diverse clinical subgroups. Multivariate analysis confirmed independent prognostic value of KAT2A expression in the established nomogram model. Functional annotation revealed enrichment of KAT2A-associated genes in critical biological processes and signaling pathways. Moreover, KAT2A expression exhibited correlations with mutational profiles and immune cell infiltration patterns in LUAD. Both in vitro and in vivo experiments demonstrated that KAT2A knockdown significantly suppressed tumor cell proliferation and immune evasion mechanisms, induced apoptosis, and inhibited tumor growth. These findings suggest that KAT2A may serve as a potential prognostic biomarker for LUAD, with therapeutic implications through its regulatory role in immune evasion pathways.

Individuals with rheumatoid arthritis (RA) are at a significantly increased risk of developing lung cancer (LC), with a 30%-40% higher incidence compared to the general population. Although a link between the two conditions has been established, the molecular mechanisms and genetic factors remain not fully elucidated. This study aims to uncover the potential associations between LC and RA through an integrative approach of transcriptomics and genomics analysis.

Our study was aimed to established imaging models that can predict the prognosis of breast cancer patients based on IL18, so as to facilitate the formulation of more individualized treatment plans during the treatment.

The malignant progression of colorectal cancer (CRC) is closely related to cell stemness, but its regulatory mechanism has not been fully elucidated. This study found that ADAMTS14 was significantly highly expressed in CRC tissues and cell lines and was associated with poor prognosis in patients. Functional experiments have confirmed that ADAMTS14 enhances the stemness characteristics (such as upregulation of ALDH1A1, ALDH1A3, and CD133 expression) and spheroidization ability of CRC cells by activating the Wnt signaling pathway. Further mechanism studies have shown that the transcription factor ONECUT2 is also highly expressed in CRC and indicates a poor prognosis, and it can directly activate its transcription by binding to the ADAMTS14 promoter region. In conclusion, this study has revealed a novel mechanism by which the ONECUT2/ADAMTS14/Wnt axis regulates the stemness of CRC cells, providing a potential molecular target for targeted intervention.