Glutathione S-transferase omega 1 (GSTO1) is overexpressed in a variety of cancers and plays an important role in the promotion of tumor proliferation and metastasis. Nevertheless, the function of GSTO1 in cervical cancer (CC) is unknown. Immunohistochemistry (IHC) was applied to observe GSTO1 protein levels in CC tissues. Cell proliferation, migration, and invasion capabilities were assessed using CCK8, EdU, plate cloning assays, and Transwell experiments in vitro. Flow cytometry was employed to analyze cell cycle progression and reactive oxygen species (ROS) levels. A subcutaneous xenograft model was utilized to observe cell growth in vivo. Cell stemness was assessed via sphere formation assay. Transcriptome sequencing and enrichment analysis were conducted to explore GSTO1-related signaling pathways. The proteins linked to cell cycle regulation, stemness, epithelial-mesenchymal transition (EMT), and the PI3K/AKT/mTOR signaling pathway were identified through western blotting and IHC. In this study, GSTO1 was highly expressed in CC tissues and associated with poor prognosis of patients. Knockdown of GSTO1 suppressed CC cell proliferation in vivo and in vitro and inhibited the cell cycle, stemness, migration, and EMT as in C1-27 treatment. Conversely, down-regulation of GSTO1 promoted ROS production in CC cells. RNA sequencing indicated that GSTO1 mediated the activation of the PI3K/AKT signaling pathway. In addition, silencing GSTO1 decreased the phosphorylation of PI3K, AKT, and mTOR proteins. Interestingly, 740 Y-P (PI3K activator) reversed the inhibitory effects of GSTO1-induced cell proliferation, cycle, stemness, and EMT via the PI3K/AKT/mTOR signaling axis. GSTO1 was important in CC progression through the PI3K/AKT/mTOR pathway and could serve as a promising therapeutic target.

Hepatocellular carcinoma (HCC) is characterized by pronounced heterogeneity and extensive angiogenesis. However, anti-angiogenic therapies often show limited clinical benefit due to therapeutic resistance. Understanding endothelial cell heterogeneity and identifying key regulators of tumor angiogenesis are therefore essential for improving treatment strategies.

Mismatch repair-proficient (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC) remains largely refractory to immunotherapy due to its intrinsically immunologically cold tumor microenvironment. Although frontline chemotherapy combined with immune-induction strategies can improve progression-free survival, these benefits have not translated into overall survival gains. Importantly, late-line trials such as LEAP-017 suggest that biologically meaningful immune activity may be masked by dilution effects in unselected populations. This review advocates a shift from empirical treatment approaches toward mechanism-driven precision stratification in refractory pMMR/MSS mCRC. We highlight two complementary immune activation strategies: tumor microenvironment remodeling via tyrosine kinase inhibitor-mediated vascular normalization, and intensified immune priming through cytotoxic T-lymphocyte-associated protein 4 blockade. To address persistently low response rates, we propose an integrated precision framework incorporating genomic repurposing, anatomical filtering, and multimodal synergy, aiming to translate transient immune activation into durable survival benefit.

Dipeptidyl peptidase 4 (DPP4) plays diverse physiological roles, but its pan-cancer significance and immunomodulatory functions remain poorly characterized.

Codon usage bias is a fundamental feature of the genetic code, yet its impact on messenger RNA translation is incompletely defined. Here, we integrate comparative genomics, human tissue proteomes, large cancer cell line, and patient cancer datasets to reveal a conserved codon-bias axis. Across mammals, we show that GC-biased gene conversion drives human-specific GC3 (third codon nucleotide bias score) drifts, yet the functional dichotomy is maintained: A/T-ending codons associate with proliferation and RNA processing, while G/C-ending (Third nucleotide Guanine or Cytosine) codons associate with differentiation and neuronal functions. At the isoacceptors level, synonymous codons segregate into distinct functional categories. To mechanistically connect codon usage to cancer, we introduce the ANN- and m7G-indices, capturing codons decoded by transfer RNA (tRNA) modifications t6A and m7G. Both indices negatively correlate with GC3 and enrich for pro-oncogenic proliferative pathways. Human tissue proteomes reveal strong codon bias discordance between RNA and protein levels, with nervous system tissues enriched for G/C-ending codons while proliferative organs are A/T-biased. Analysis of 2600 cancer cell lines and 21 cancer types revealed heterogeneous codon preferences in cancer cell lines but a global A/T-ending shift in human cancer-upregulated proteins. These findings establish synonymous codon divergence and tRNA modification indices as key determinants of translational reprogramming in health and cancer.

Unlike normal colon cells with butyrate acid as the main energy source, cancerous colon cells are more inclined to use glucose. However, the mechanisms of the investigation into the modulatory role of butyrate metabolism within the pathophysiology of colorectal cancer (CRC) remains insufficiently explored.

Solid pseudopapillary neoplasms (SPNs) are rare pancreatic tumors that are indolent but occasionally present with metastatic or locally invasive disease. Although recurrent CTNNB1 exon 3 mutations define their molecular background, the clinicopathological and molecular features associated with these less common presentations remain incompletely characterized. This retrospective study included 62 patients diagnosed with SPN between 2000 and 2025. Clinicopathological and immunohistochemical features, including β-catenin, progesterone receptor (PR), androgen receptor (AR), and BAP1, were evaluated. Targeted sequencing was performed in a subset of cases with metastatic or locally invasive disease (n = 5). Patients showed a wide age range (8-71 years), female predominance (54/62, 87.1%), and a mean tumor size of 7.2 cm. Lymphovascular invasion was rare (1/59, 1.7%). Metastatic or locally invasive SPNs (n = 8) more frequently showed higher Ki-67 values (median, 5%; range, 1%-15%), increased mitotic activity (2/8, 25%), and capsular/parenchymal invasion (6/8, 75%), while perineural invasion was absent. All tumors demonstrated nuclear β-catenin expression, with PR and AR positivity (50/59, 84.7% and 47/57, 82.5%, respectively). PR expression was higher in AR-positive cases (43/47, 91.5% vs. 6/10, 60%). BAP1 loss was identified in 13/57 cases (22.8%). Targeted sequencing consistently identified CTNNB1 exon 3 mutations. Additional low-frequency molecular alterations affecting genes involved in cell cycle regulation, chromatin remodeling, and signaling pathways, including CDKN2A and BAP1, were observed. During a mean follow-up of 97.2 months, distant metastasis occurred in 4/62 patients (6.5%) and locally invasive disease in 4/62 (6.5%), with an overall survival rate of 95%. Overall, these findings highlight the biological heterogeneity of SPNs and indicate that, despite a shared molecular background, aggressive behavior is not defined by a single reproducible pathological or molecular feature.

Non-small cell lung cancer (NSCLC) is the predominant lung cancer subtype with high mortality rate. Drug resistance and immune evasion limit its therapeutic outcomes. Specific mechanism of the oncogenic ZFP36L1 in NSCLC remains unclear.

NUT carcinoma is a rare and highly aggressive malignancy characterized by the rearrangement of the NUTM1 gene. It typically arises in midline structures, including the respiratory tract. Due to its rarity and poor prognosis, early diagnosis and effective treatment remain challenging. This report presents two cases of NUT carcinoma occurring in the respiratory tract, additionally, a review of the literature is provided to enhance understanding of this disease. Both patients were young females, one tumor was located in the larynx and the other in the left main bronchus. Endoscopic forceps biopsy samples revealed tumor growth beneath the superficial mucosal epithelium, arranged in sheets, cords, or nests with extensive necrosis. The tumor cells were uniform in size, with eosinophilic cytoplasm, ill-defined borders, and round or oval nuclei showing hyperchromasia and a high nuclear-to-cytoplasmic ratio. One case showed focal areas with squamous differentiation. Immunohistochemically, tumor cells were positive for P40, P63, and NUT, and fluorescence in situ hybridization detected NUT gene rearrangement, confirming the diagnosis of NUT carcinoma. One patient experienced rapid disease progression despite receiving chemotherapy and died within five months. Another patient declined further treatment after diagnosis. NUT carcinoma is a rare and aggressive malignancy of the respiratory tract with a poor prognosis. Early diagnosis through molecular testing is crucial for appropriate management. However, diagnosis is often delayed until advanced stages, contributing to low survival rates. Increased awareness of this tumor among clinicians and pathologists may facilitate earlier detection and potentially improve patient outcomes.

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumour associated with a poor prognosis. Recent studies have suggested that ribonucleotide reductase subunit M2 (RRM2) could promote tumour progression. This study aims to explore the expression, function and mechanism of RRM2 in ICC by regulating ferroptosis through the HIF-1α signalling pathway.

Kirsten rat sarcoma viral oncogene homolog (KRAS) is the most commonly mutated oncogene in solid tumors, detected in up to 30% of lung adenocarcinomas. This study aimed to address gaps in the literature by analyzing KRAS mutations (KRASM) in a large Australian population.

Intramuscular myxoma (IM) is a benign tumor that harbors GNAS missense variants. Distinguishing IM from low-grade myxofibrosarcoma (LGMFS) is challenging due to similarities in imaging and histological features. While molecular analysis aids differentiation, the low number of tumor cells available for DNA extraction necessitates highly accurate detection methods for variant identification. The aim of this study was to delineate molecular characteristics using next-generation sequencing (NGS) and to propose an optimal screening method in a clinical setting to differentiate IM from LGMFS.

Ovarian cancer exhibits high molecular heterogeneity and metastatic potential, contributing to its status as a leading cause of gynecologic cancer mortality. Cell polarity is essential in tumorigenesis, yet the role of Crumbs family proteins (CRBs), key regulators of apical-basal polarity, in epithelial ovarian cancer (EOC) remains unclear. In this study, we analysed CRB expression profiles using TCGA and GEO datasets, and validated our findings through immunohistochemical staining of ovarian tumour tissue microarrays. Among CRBs, CRB2 was significantly overexpressed in EOC tissues and correlated with poor patient prognosis. Functional assays revealed that CRB2 enhances ovarian cancer cell proliferation, migration, and invasion, while suppressing apoptosis. Immunofluorescence staining of planar cell polarity markers demonstrated that CRB2 induces polarity alterations in EOC cells. Furthermore, Western blot analysis suggested that CRB2 may activate the Wnt/planar cell polarity (PCP) signalling pathway, contributing to tumour progression. These findings identify CRB2 as a key modulator of cell polarity and a potential driver of EOC aggressiveness. CRB2 may serve as a novel prognostic biomarker and therapeutic target for epithelial ovarian cancer.

Pituitary adenomas (PAs) are common intracranial tumours, and invasiveness in nonfunctioning invasive pituitary adenomas (NIPAs) predicts poor prognosis. The molecular mechanisms driving this phenotype remain unclear. This study explored the role of nuclear receptor subfamily 3 group C member 1 (NR3C1) in NIPA invasiveness and its regulation of Wnt signalling. mRNA expression profiles of 32 PA samples were generated by RNA-seq, and proteomic data from 19 samples were obtained by mass spectrometry. Immune-related differentially expressed genes (DEGs) were retrieved from GeneCards. Weighted gene coexpression network analysis identified modules and hub genes linked to invasiveness, while machine learning methods (support vector machine, LASSO, random forest) prioritised key genes. Gene set enrichment analysis (GSEA) assessed pathways associated with candidate gene expression. NR3C1 expression and function were validated by immunohistochemistry, Western blotting and invasion assays. Integration of transcriptomic, proteomic and immune-related datasets yielded 11 overlapping genes, with NR3C1 emerging as the top candidate. NR3C1 was significantly upregulated in NIPAs and demonstrated good discriminatory power by ROC analysis. GSEA associated high NR3C1 expression with Wnt pathway activation. Functional experiments confirmed that NR3C1 overexpression enhances the invasive capacity of PA cells. NR3C1 promotes the invasive phenotype of NIPAs by activating Wnt signalling. These findings suggest NR3C1 as a potential biomarker and therapeutic target for invasive pituitary adenomas.

Circulating tumor DNA (ctDNA) analysis has emerged as a pivotal minimally invasive tool for early detection, monitoring, and treatment stratification in cancer patients. However, the accuracy and reliability of ctDNA assays are profoundly influenced by preanalytical variables. This review discusses the impact of biological features (circadian rhythm, age, and sex), lifestyle factors (diet, smoking, and physical activity), as well as technical aspects such as hemolysis, leukocyte lysis, and delayed plasma separation on ctDNA integrity and concentration. Fluctuations in ctDNA levels driven by these factors highlight the need for clear guidelines regarding precollection timing, dietary restrictions, and sample processing. Furthermore, the adoption of harmonized protocols is essential to reduce variability and improve reproducibility across clinical and research settings.

Chondrosarcoma (CS) has a prognosis largely influenced by tumor grade. Although IDH mutations have been reported in CS, impact on patient`s survival remains controversial. This study aims to assess prognostic relevance of IDH mutations on disease-specific survival (DSS), metastasis-free survival (MFS), and local recurrence-free survival (RFS), in a large cohort of CS patients.

Ferroptosis, the most common programmed cell death process, and immune checkpoints play increasingly prominent roles in glioma. However, the effects of ferroptosis on immune checkpoints on glioma remain unclear. The intracellular ROS levels of ferroptotic glioma cells were observed via fluorescence microscopy. The extracellular Acetyl-HMGB1 content of ferroptotic glioma cells was detected via an ELISA kit. Transwell chambers (8.0 μm) were used to detect the invasion ability of ferroptotic glioma cells. The ability of ferroptotic glioma cells to proliferate was detected via the CCK-8 reagent. The apoptosis of ferroptotic glioma cells was detected via an Annexin V-FITC apoptosis kit. The transcriptional levels of four immune checkpoints (CD80, CD155, HMGB1, and galectin-9) in ferroptotic glioma cells were detected via RT-PCR. Ferroptosis in glioma cells promotes the release of acetyl-HMGB1 and autophagy is involved in this process. Inhibiting extracellular acetyl-HMGB1 while inducing ferroptosis promoted the invasion and proliferation of glioma cells and inhibited apoptosis. Ferroptosis downregulated the transcription of CD155 and galectin-9 in glioma cells, but inhibition of extracellular acetyl-HMGB1 reversed the effect of ferroptosis on the downregulation of galectin-9 transcription. In conclusion, ferroptosis downregulates galectin-9 transcription via extracellular acetyl-HMGB1, thereby inhibiting the biological behavior of glioma cells.

Tumor heterogeneity in breast cancer is well recognized, but research has largely focused on primary tumors, while metastatic lesions, particularly brain metastases (BM), remain understudied. With the rising incidence of BM in metastatic breast cancer (MBC) and their poor prognosis, a deeper understanding of the molecular mechanisms driving BM formation, progression, and immune evasion is crucial for developing better therapeutic strategies. We performed an integrated analysis of BM and matched primary breast tumors using immunohistochemistry, in-situ hybridization, tumor-infiltrating lymphocyte (TIL) quantification, and bulk RNA sequencing. Tumor receptor status, gene expression profiles, immune cell composition, and pathway alterations were analyzed in ten patients with paired samples. Changes in receptor status were observed between primary tumors and BM, including alterations in estrogen receptor and HER2 expression. RNA sequencing revealed differentially expressed genes and pathways, with an apparent downregulation of immune-related genes in BM. Immune profiling suggested a shift in the tumor microenvironment, with BM showing lower B- and CD8 + T-cell infiltration and a relative increase in M2 macrophages and follicular helper T-cells. While these findings are descriptive and limited by sample size, they point towards a potentially more immunosuppressive milieu in BM that may contribute to immune evasion and reduced responsiveness to checkpoint inhibitor therapy. Our study highlights molecular and immunological differences between primary breast tumors and BM. The altered immune landscape in BM, characterized by diminished TIL infiltration and an increase in immunosuppressive cells, warrants further investigation in larger, more homogeneous cohorts.

MRVI1 is a multifaceted gene whose functions in cancer vary across tissue types, acting either as a tumor-promoting or tumor-suppressive factor. In colorectal cancer, MRVI1 functions downstream of p53, and its loss enhances malignant phenotypes; however, the effects of MRVI1 overexpression have remained unclear. In this study, we established HCT116 colorectal cancer cells stably overexpressing MRVI1 to examine its functional impact. Western blot analysis confirmed robust expression of the V5-TurboID-MRVI1 fusion protein in the established cell line. Cell proliferation assays showed that MRVI1 overexpression markedly reduced cell growth compared with control cells under standard culture conditions. Trypan blue staining demonstrated that MRVI1 overexpression did not increase cell death, indicating that the reduction in cell number reflects a cytostatic rather than cytotoxic effect. These findings provide direct evidence that MRVI1 suppresses the proliferation of colorectal cancer cells when overexpressed. Combined with previous reports demonstrating that MRVI1 knockdown promotes proliferation and invasive behavior in colorectal cancer cells, our results support the view that MRVI1 contributes to p53-associated growth control in this tumor lineage. These observations further reinforce the concept that MRVI1 is a context-dependent, multifaceted cancer-associated gene.

Cancer progression is governed by a dynamic interplay between genetic alterations and epigenetic modifications, which shape tumor adaptation, immune evasion, and therapy resistance. Among these modifications, epigenetic regulation of autophagy, a cellular process critical for maintaining homeostasis, has emerged as a key player in cancer biology. While autophagy suppresses tumor initiation by eliminating damaged organelles and reducing oxidative stress, tumors can hijack this process to sustain survival under metabolic stress and promote resistance to chemotherapy, radiotherapy, and immunotherapy. This review explores the intricate crosstalk between DNA methylation, histone modifications, and non-coding RNAs in controlling autophagy-related genes and their dual role in cancer progression. We also highlight the therapeutic potential of targeting epigenetic modulators (HDAC and DNMT inhibitors) and autophagy regulators to overcome multidrug resistance. Understanding the epigenetic-autophagy axis provides novel insights into cancer treatment, emphasizing the need for personalized approaches that balance autophagic activity to enhance therapy efficacy and improve patient outcomes. This emerging field presents a promising frontier for epigenetic-driven precision medicine in oncology.