Osteosarcoma is an aggressive bone malignancy with elusive core driving mechanisms. Dysregulated expression of integrin α2 (ITGA2) promotes malignant progression in multiple cancers, yet its role in osteosarcoma and correlation with bone destruction remain poorly understood. This study investigated the potential role of ITGA2 in osteosarcoma progression and therapeutic targeting.

Small cell lung cancer is the most malignant subtype of lung cancer and has a poor prognosis. However, the mechanism is not well understood. The aim of this study was to investigate the characteristics of gene mutation in small cell lung cancer patients and the differences in HLA-I alleles between small cell lung cancer patients and healthy controls, and to explore the effects of gene mutations and specific HLA-I alleles on small-cell lung cancer from the perspective of immune regulation.

Synovial sarcoma (SS) is a rare but aggressive soft tissue malignancy characterized by a high rate of pulmonary metastasis and limited response to conventional therapies. Hypoxia, a common feature of tumor microenvironment, has been implicated in cancer progression, yet its specific contribution to metastatic dissemination in SS remains insufficiently characterized.

Nuclear protein in testis (NUT) carcinoma (NC) in children is a rare tumor with highly aggressive nature and dismal prognosis.

Salivary gland carcinoma is a rare malignancy with diverse histological subtypes and poor prognosis, particularly when diagnosed at advanced stages. Recent evidence suggests that biomarkers such as CD73 and VEGF may play important roles in tumor progression and immune evasion, yet limited studies have evaluated their expression and clinical significance in Southeast Asian populations. This study aimed to determine the expression rates of CD73 and VEGF in salivary gland carcinoma and identify clinicopathological factors associated with their expression in a Vietnamese patient cohort.

Pericytic tumors are a group of soft tissue neoplasms characterized by a hemangiopericytoma (HPC)-like pattern. The underlying genetic lesion of pericytic neoplasms is still obscure; however, recent advances in molecular pathology have enabled a mechanistic understanding and accurate diagnosis of these tumors. Nevertheless, a subset of unclassified pericytic tumors continues to present substantial diagnostic challenges, potentially impacting clinical decision-making and therapeutic strategies.

Disarray in microRNA (miRNA) strand selection is associated with multiple tumors. However, the mechanisms underlying miRNA strand selection-driven temozolomide (TMZ) resistance in glioblastoma (GBM) remain unexplored.

Gliomas, notably high-grade variants, dominate the spectrum of central nervous system (CNS) malignancies, characterized by aggressive behavior and diffuse invasion. Despite advances in tumor immunology, patient outcomes are stagnant. Amino acid metabolism is pivotal in glioma progression, driving the quest for metabolic targets. Bioinformatics allows deep dives into large-scale patient data from TCGA, CGGA, and GEO. Comparative studies on glioma amino acid metabolism have identified genes associated with tumor characteristics and patient survival. This yields an amino acid metabolism-based risk score model, which elucidates key biological processes and signaling pathways. Our holistic strategy clarifies amino acid metabolism's role in glioma onset, paves the way for targeted therapies. Precise analysis and strategic targeting of metabolic pathways hold great promise for improving glioma treatment, offering hope to patients battling this relentless CNS malignancy.

Cisplatin resistance significantly limits the effectiveness of chemotherapy in esophageal squamous cell carcinoma (ESCC). Understanding the molecular mechanisms driving resistance is essential for improving treatment outcomes.

BRI3BP, an RNA-binding protein upregulated in multiple cancers, plays an undefined role in hepatocellular carcinoma (HCC). This study investigates its diagnostic and prognostic potential in HCC. Multi-omics analysis of TCGA and GEO data identified BRI3BP-interacting genes and enriched pathways. Genomic and epigenetic alterations were assessed using cBioPortal and MethSurv. Immune infiltration was profiled via ssGSEA and TIMER 2.0. Prognostic relevance was validated through survival analysis, Cox regression, and experimental assays. BRI3BP was overexpressed in HCC and correlated with advanced tumor stage, shorter overall survival (OS), and disease-free survival (DFS). Functional enrichment linked BRI3BP to cell cycle regulation, Rho GTPase activity, and copper homeostasis. Analysis of transcriptomic data revealed that BRI3BP expression also significantly correlated with immune cell infiltration and an immunosuppressive microenvironment, validated by immunohistochemistry showing reduced CD8 + and increased CD68 + cells in high-BRI3BP samples. In vitro, BRI3BP overexpression promoted HCC cell migration and invasion and activated the ROCK signaling pathway, suggesting potential involvement in tumor progression. Drug sensitivity assays confirmed lower lapatinib IC50 in overexpression models. High BRI3BP expression correlates with aggressive HCC phenotypes, poorer survival, and dysregulated oncogenic pathways, supporting its role as a prognostic biomarker and candidate therapeutic target.

We investigated the prognostic significance of cholesterol metabolism-related genes (CMRGs) and estrogen metabolism-related genes (EMRGs) in lung adenocarcinoma (LUAD). Transcriptomic and clinical data from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) databases were analyzed. Iterative sure independence screening and least absolute shrinkage and selection operator (ISIS-LASSO) Cox regression identified prognostic CMRGs and EMRGs. Two risk scores-Cholescore and Estrogenscore-were constructed and validated. High Cholescore was associated with poor overall survival (OS), reduced immune infiltration, low immune checkpoint expression, and high tumor purity, suggesting an immunosuppressive tumor microenvironment. Estrogenscore also independently predicted LUAD prognosis. Mediation analysis revealed that estrogen-related pathways partially mediated the impact of cholesterol metabolism on prognosis. A significant interaction between Cholescore and Estrogenscore was identified, and patients with both high scores had the worst OS and lowest predicted immunotherapy benefit. Combining the two scores significantly improved the area under the curve (AUC) for 1-5 years OS prediction. These findings suggest that integrating cholesterol and estrogen metabolism signatures can improve LUAD prognostic stratification and provide molecular insights into tumor-immune interactions and immunotherapy response prediction.

Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases are a highly evolutionarily conserved protein family. Their members are closely associated with DNA damage repair and involved in the genesis and progression of various tumors. Additionally, DNA damage contributes to the onset and progression of kidney renal clear cell carcinoma (KIRC). We collected KIRC samples from public datasets and applied clustering and machine learning methods to analyze the correlation between APOBEC families and KIRC prognosis. Based on APOBEC family expression, we classified KIRC patients into two clusters, which showed significant differences in drug sensitivity and survival. Subsequently, we compared the difference between the traditional coxph model and the machine learning model in predicting the prognosis of KIRC patients, and the results showed that the machine learning has better predictive ability. In addition, the study also predicted potential small-molecule drugs for KIRC treatment. This study proposes a method for KIRC classification and prognosis prediction based on APOBEC family expression. It may help clinicians predict patient drug sensitivity and survival, thereby guiding clinical medication and long-term treatment follow-up.

This study investigated the prognostic significance of m6A-related programmed cell death (PCD) genes in acute lymphoblastic leukemia (ALL). Transcriptomic data from the TCGA-ALL and GSE48558 datasets were analyzed to identify m6A-related PCD genes (corgenes), which were then intersected with 3,063 differentially expressed genes (DEGs), resulting in 23 candidate genes. Univariate Cox regression and LASSO regression analyses identified CFLAR and CDK4 as key prognostic genes, facilitating the construction of a high-accuracy risk prediction model. Gene set enrichment analysis (GSEA) revealed significant pathway differences between the high-risk group (HRG) and the low-risk group (LRG), including olfactory transduction, circadian rhythm, and protein export (adj.P < 0.05). Sensitivity analysis of 60 chemotherapy agents indicated that Bicalutamide was more effective in LRG, while ATRA, CCT018159, PHA-665752, and PLX4720 demonstrated greater efficacy in HRG. RT-qPCR validation confirmed upregulation of CDK4 and downregulation of CFLAR in ALL samples (P < 0.05). This study offers important theoretical support for the prognostic evaluation and personalized treatment strategies in ALL.

Accurate detection of somatic variants in tumors is of critical importance and remains challenging. Current methods typically require matched normal samples for reliable detection, which are often unavailable in real-world research and clinical scenarios. Without a matched normal sample, more proficient algorithms are required to distinguish true somatic variants from germline variants and technical artifacts. However, existing tumor-only somatic variant callers that were designed for short-read sequencing data are not able to work well with long-read data. To fill the gap, we present ClairS-TO, a deep-learning-based method for long-read tumor-only somatic variant calling. ClairS-TO uses an ensemble of two disparate neural networks trained from the same samples but for opposite tasks-how likely/not likely a candidate is a somatic variant. Benchmarks using COLO829 and HCC1395 cancer cell lines show that ClairS-TO outperforms DeepSomatic and smrest in ONT and PacBio long-read data. ClairS-TO is also applicable to short-read data and outperforms Mutect2, Octopus, Pisces, and DeepSomatic. Extensive experiments across various sequencing coverages, variant allelic fractions, and tumor purities support that ClairS-TO is a reliable tool for somatic variant discovery. ClairS-TO is open-source, available at https://github.com/HKU-BAL/ClairS-TO .

Triple-negative breast cancer (TNBC) is characterized by its high aggressiveness and treatment resistance, with limited therapeutic options and especially a lack of effective targeted therapeutic strategies. This study focuses on the role and regulatory mechanisms of super enhancer long non-coding RNA (SE-lncRNA) in TNBC. Through in-depth analysis of TCGA database, we revealed the specific expression pattern of SE-lncRNA in TNBC, and found that downregulation of RP11-54O7.17 was significantly correlated with poor prognosis of TNBC patients, which was experimentally verified. Both in vitro and in vivo results confirmed that RP11-54O7.17 overexpression effectively suppressed the proliferation and metastasis of TNBC. Further exploration showed that RP11-54O7.17 directly interacted with the S100A4 protein through its conserved L2b-type repeat structural fragment, promoted S100A4 binding to HSP70, targeting S100A4 degradation via the autophagy-lysosome pathway, which in turn blocked the activation of S100A4-STAT3 signaling axis. Moreover, RP11-54O7.17 delivered via liposome demonstrated significant anti-TNBC efficacy in an in vivo model without observing significant systemic toxicity. This study elucidates the regulatory role and molecular mechanism of RP11-54O7.17 in TNBC, which provides a strong scientific basis and potential therapeutic targets for the development of novel SE-lncRNA-based therapeutic strategies.

Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer associated with a poor prognosis. However, there have been few advancements in improving the survival of SCLC patients in recent decades. This study shows that the S100A9 protein is highly expressed in SCLC patients and several highly aggressive SCLC cell lines. Furthermore, we showed that S100A9 expression inversely correlates with overall survival in SCLC patients. S100A9 increases the survival and migration of SCLC cells by activating Akt and GSK3α/β/Snail pathways. In addition, S100A9 reduces tumor cell autophagy through MAGE-A3. S100A9 depletion or pharmacological inhibition using tasquinimod reduced tumor growth and metastasis in vivo. Importantly, we observed that S100A9 downregulation or tasquinimod treatment alone or combined with cisplatin reduces the recruitment of MDSCs. Furthermore, tasquinimod treatment alone or combined with cisplatin significantly enhanced tumor infiltration of activated CD8+ (CD69-positive) T cells. Overall, our results, for the first time, show that S100A9 enhances SCLC progression and metastasis by altering the tumor microenvironment, and its inhibition using tasquinimod alone or in combination with chemotherapy could be developed as a promising therapeutic strategy for SCLC.

Blood-based multi-cancer early detection (MCED) has the potential to simultaneously screen for multiple deadly cancers with high positive predictive value. To assess real-world performance, we evaluated the Galleri® MCED test (GRAIL, Inc.) across 111,080 individuals (median age 58 years, 55.5% males). This MCED test analyzes methylation patterns of cell-free DNA to detect presence of a cancer signal and predict the anatomical cancer signal origin (CSO) to facilitate diagnostic evaluation. Cancer signal detection rate was 0.91% (1011/111,080), consistent with clinical studies and independent modeled values. Providers reported clinical outcome for 459 of 1011 individuals with cancer signal detected MCED tests. Of these, 258 had an invasive cancer diagnosis, spanning 32 cancer types. The MCED test correctly predicted the CSO in 87% of cases with a reported cancer type, consistent with previous clinical studies. CSO enabled efficient workup in most patients, with a median 39.5 days from result receipt to cancer diagnosis.

Accumulating data have shown that circRNAs act pivotal roles in cancer progression. However, the role and molecular mechanism of circRNAs in melanoma remain undocumented. GEO dataset was used to identify the differentially expressed circRNAs between melanoma and normal tissues, and the expression and prognosis of circANKRD52 (hsa_circ_0026926) in melanoma were assessed by qRT-PCR analysis. EdU, Transwell, Flow cytometry analysis, human umbilical vein endothelial cells (HUVECs) coculture assay as well as in vivo tumourigenesis models were utilised to assess cell growth and invasion. The specific binding between circANKRD52 and miR-141-3p was confirmed by bioinformatic analysis, RIP, RNA pull-down, and luciferase reporter assays. The effect of circANKRD52 or miR-141-3p on PRKACB expression was evaluated by Western blot assay. We found that circANKRD52 was upregulated in melanoma tissue samples and cell lines and associated with poor survival and tumour recurrence in patients with melanoma. Knockdown of circANKRD52 repressed the growth and invasion of melanoma cells in vitro and in vivo, whereas ectopic expression of circANKRD52 promoted these effects. Moreover, circANKRD52 could bind to miR-141-3p, leading to upregulation of PRKACB, and downregulation of miR-141-3p restored melanoma cell growth and invasion. Our findings demonstrate that circANKRD52 promotes the growth and angiogenesis of melanoma cells by sponging miR-141-3p and upregulating PRKACB.

Gynecologic malignancies are a heterogenous group of tumors driven by a wide variety of molecular alterations. Molecular profiling has become increasingly useful in the development of novel biomarkers, screening tools, and targeted therapeutic agents. The purpose of this article is to provide an overview of the current usage of personalized medicine in the field of gynecologic oncology.

The mitogen-activated protein kinase (MAPK) cascade is a critical pathway involved in cancer cell survival as well as resistance to drug therapy. Phosphorylation of extracellular signal-regulated kinase 1 (ERK1) and extracellular signal-regulated kinase 2 (ERK2), the final effectors of the MAPK pathway, results in activation of multiple substrates that are responsible for cellular proliferation, differentiation, survival, and migration. This review will focus on our current understanding of 2 types of rare gynecologic cancers that frequently harbor MAPK alterations, low-grade serous ovarian cancer and mesonephric/mesonephric-like gynecologic neoplasms, and how this understanding may change our future treatment of these diseases.