Cancer metastasis, the process by which tumor cells spread from the primary site to other organs, is one of the leading causes of death in cancer patients. However, due to its complexity and unpredictability, the study of cancer metastasis remains a significant challenge in medicine. In recent years, with the advancement of high-throughput sequencing technologies and single-cell transcriptomics, we could gain a deeper understanding of the molecular mechanisms and cellular heterogeneity underlying cancer metastasis. There is an accumulating volume of publicly available cancer metastasis research data. Nevertheless, these resources lack proper organization, hindering systematic analysis.

Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer with limited therapeutic options. Although cisplatin is recommended as a first-line treatment, its clinical efficacy is hindered by the rapid development of drug resistance, highlighting the urgent need for effective strategies to overcome cisplatin resistance.

Endometrioid borderline ovarian tumor (EBOT) is rare and frequently misdiagnosed. This study aims to investigate the clinicopathological features, immunohistochemical characteristics, differential diagnosis, therapeutic approaches and disease prognosis, thereby establishing a robust foundation to mitigate misdiagnosis risks and deepen insights into the pathological diagnosis of this disease.

Despite an initial favorable response of EGFR-mutant non-small cell lung cancer (NSCLC) to osimertinib, an EGFR tyrosine kinase inhibitor (TKI), resistance to this drug inevitably develops. Whereas genetic mechanisms for such acquired resistance have been identified, the molecular mediators of resistance induction have remained unclear.

The high incidence of recurrence and metastatic disease remain the major issues for papillary thyroid cancer (PTC) patients. Previous studies have demonstrated that Syndecan-2 (SDC2) plays a key role in multiple cancers progression. However, the potential role of SDC2 in PTC progression and recurrence remains unclear.

Circular RNAs (circRNAs) play a crucial role in the initiation and development of cancers. Understanding circRNAs' functions and molecular mechanisms in tumor development is expected to reveal new diagnostic indicators and therapeutic targets of prostate cancer (PCa). In our study, we identified a new circRNA hsa-circ-0057553 (circSLC39A10) in PCa from a bioinformatic microarray analysis. The levels of circSLC39A10 were observed to be markedly elevated in both prostate cancer cells and tissues. This increased expression was associated with multiple clinicopathological features, suggesting its potential as a new diagnostic indicator for PCa. CircSLC39A10 exhibited oncogenic effects on the proliferation, migration, invasion, and metastasis of prostate cancer cells both in vivo and in vitro. CircSLC39A10 was identified as a factor that promoted the malignant progression of PCa cells through the miR-936/PROX1/β-catenin pathway, ultimately leading to the activation of Wnt signaling. Overall, circSLC39A10 is an oncogenic circRNA with potential as a biomarker for PCa. The identified circSLC39A10/miR-936/PROX1/β-catenin axis shows promise as an innovative therapeutic target for PCa.

To identify the clinical and molecular factors that effectively predict pathological complete response (pCR) and assess the safety of patients receiving neoadjuvant combination immunotherapy.

Distant metastasis remains the primary cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, it is essential to explore the regulatory mechanisms underlying NPC metastasis. Ets variant 5 (ETV5) is a transcription factor demonstrated to be overexpressed in various malignancies. However, the function of ETV5 in NPC is poorly characterized. We aim to investigate the function and mechanisms of ETV5 in NPC development. We assessed ETV5 expression in nasopharyngeal carcinoma tissues from 99 patients using quantitative immunohistochemistry. ETV5 levels in the cell lines 6-10B, CNE2, 5-8F, and S18 were determined using Western blotting. Cell proliferation, migration, and invasion capabilities were assessed using colony formation, scratch, and Transwell assays. The binding of ETV5 to promoter of leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) was detected by dual luciferase reporter gene detection system. We found that ETV5 overexpression was significantly correlated with poorer prognosis in NPC patients. Based on endogenous ETV5 expression, ETV5 overexpressing and downregulation cell lines were established. Functional analyses were conducted using CCK-8, colony formation, wound healing, and transwell assays. Elevated ETV5 expression promotes NPC cell proliferation and invasion migration, while knocking down ETV5 has the opposite effect. Mechanistically, ETV5 transcriptionally activates of LGR4 by directly binding to its promoter region. Our study revealed that ETV5 induces cell proliferation, invasion and migration by upregulating LGR4 in NPC. ETV5/LGR4 signaling may serve as a therapeutic target for NPC patients.

Breast cancer remains one of the most deadly cancers, highlighting the urgent need for better prognostic markers and treatment targets. Emerging evidence suggests that inflammation-driven immune dysregulation plays a pivotal role in breast cancer progression and therapy resistance. Single-cell RNA sequencing and comprehensive gene network analysis based on inflammation identified FLT3LG as a crucial protective factor in breast cancer. Tumors with lower FLT3LG expression showed poorer survival outcomes across multiple patient cohorts. Functional analysis revealed its role in immune regulation, particularly in the activation of B cells and T cells, as well as in chemokine signaling. Genetic profiling revealed distinct mutation patterns: PIK3CA mutations were enriched in tumors with high FLT3LG expression, whereas TP53 mutations predominated in tumors with low FLT3LG expression. Correlations with immune cell infiltration and checkpoint markers suggested that FLT3LG may predict enhanced responses to immune checkpoint inhibitors and certain targeted drugs. These findings support its potential as a multifunctional biomarker for prognosis and therapeutic decision making in breast cancer.

Serotonin and serotonin metabolism has for decades been understood as playing a critical role in mood disorders and has more recently also been implicated in brain tumour biology. However, in part due to the lack of direct investigation of genetic and epigenetic variation affecting serotonin pathways within human brain tissue this understanding has recently been challenged. We analysed genetic and epigenetic variation in the Monoamine oxidase A (MAOA) and serotonin transporter (5HTT) genes using 232 biobanked glioma tissue samples from 216 adult patients. We further examined the association between use of antidepressants (targeting serotonergic pathways), serotonin levels and methylation. In male patients, genetic variation in the MAOA gene was significantly associated with tissue serotonin levels. Further analysis identified five single nucleotide variants (SNVs) that may contribute to this association. In contrast, 5HTT variants were not statistically associated with serotonin pathway metabolites, nor were MAOA variants in females. Increased methylation at several 5HTT CpG sites was positively correlated with serotonin levels and negatively correlated with 5-HIAA levels. In males, one CpG site in the MAOA gene was negatively associated with the 5-HIAA/serotonin ratio, suggesting reduced enzymatic degradation of serotonin due to lower MAOA activity. Patients using antidepressants had lower tissue serotonin levels. In males, genetic variation in the MAOA gene was significantly associated with tissue serotonin levels, although this association was not mediated by methylation. Our result supports the notion that the MAOA and 5HTT genes are related to serotonin metabolism and that such metabolism is related to antidepressant use.

Gene expression and regulation with or without alternative splicing are crucial for tissues and cells to function correctly. They have been studied from three almost independent perspectives at the genome level: 1- Recognition of splicing quantitative trait loci (sQTLs), 2- Expression quantitative trait loci (eQTLs) recognition, and 3- Recognition of longer-range physical chromatin interactions between genome segments which model 3D dynamics of cells and tissues. Even though the associations between eQTLs and longer-range chromatin interactions have been previously studied, a similar relationship between sQTLs and chromatin interactions has yet to be analyzed. In this case, examining whether sQTLs control the alternative splicing of their target genes' mRNA via physically interacting genome segments is crucial. We have jointly analyzed high-throughput chromatin conformation capture (Hi-C) and sQTL datasets over eight human cancer tissues. We have discovered a positive association between the number of genes having sQTLs and chromatin interaction frequency. Such a positive association still exists when we also control for eQTLs. Additionally, sQTLs and their target genes generally exist inside identical topologically associating domains (TADs). These findings are observed over the whole set of analyzed cancer types and functional subsets of the sQTL dataset, such as survival-related sQTLs. Furthermore, tissue-specific sQTLs are statistically enriched in tissue-specific frequently interacting regions (FIREs) in 6 out of 8 human cancer tissues (Chronic Myeloid Leukemia, Colon Adenocarcinoma, Acute Myeloid Leukemia, Lung Adenocarcinoma, Prostate Cancer, Sarcoma). Our sQTL and Hi-C datasets have shown the existence of closer spatial distance between sQTLs and their target genes with possible alternative splicing across several different cancer types in humans. Such a closer spatial distance also exists, independent of whether we integrate eQTLs into the analysis. We found that sQTLs regulate alternative splicing through chromatin interactions. Source code of the analysis in this research is available on https://github.com/seferlab/sqtlhic .

The initial manifestations of nasopharyngeal carcinoma (NPC) are subtle and imperceptible, leading to unfavorable clinical outcomes and limited therapeutic alternatives among Southeast Asian populations. Deletion of chromosome 3p is a commonly observed genetic alteration in NPC. In our endeavor to elucidate the key genes and pathways driving NPC growth, we have discovered that Villin like (VILL), located at 3p22.2, functions as a novel tumor suppressor gene (TSG) with significantly diminished expression levels in NPC. This finding underscores the tremendous potential of VILL as an unexplored molecule warranting further investigation. Overexpressing VILL effectively inhibits proliferation by inducing G1 phase arrest in NPC cells while its knockdown yields contrasting effects on cell growth regulation. Furthermore, our study demonstrates that VILL targets MYC. Knockdown of VILL and overexpression of MYC significantly enhance proliferation in an immortal nasopharyngeal epithelial cell line NP69. Moreover, we are the first to report that VILL plays a tumor suppressive role in NPC. Consequently, VILL emerges as a novel prognostic biomarker and a potential therapeutic candidate for NPC.

Patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations often benefit from third-generation tyrosine kinase inhibitors (TKIs), such as aumolertinib (AUM). However, the development of drug resistance significantly limits the clinical efficacy of AUM. To address this, we established an in vitro model of AUM-resistant cell lines and performed RNA sequencing to identify resistance-associated differentially expressed genes. Using machine learning, we constructed an AUM resistance-related prognostic signature (ARRPS). Our results demonstrated that ARRPS effectively predicts the prognostic risk of patients. Notably, for patients with high ARRPS scores, the addition of CD-437 or TPCA-1 to conventional AUM treatment may help overcome drug resistance. These findings suggest that ARRPS serves as both a prognostic tool and a guide for personalized treatment strategies, potentially optimizing the clinical management of NSCLC patients.

Genes involved in absorption, distribution, metabolism, and excretion (ADME) regulate drug pharmacokinetics, yet their prognostic value in colorectal cancer (CRC) remains underexplored. This study develops an ADME-related prognostic index for colorectal adenocarcinoma (COAD). Gene expression and clinical data from 430 COAD patients in The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed ADME genes. Functional enrichment analysis, immune cell infiltration profiling, immunotherapy response prediction, and mutation burden comparison were performed between high-risk (HR) and low-risk (LR) groups. ADME genes demonstrated distinct functional patterns between risk groups. The LR group exhibited enrichment in drug metabolism pathways, whereas the HR group was predominantly associated with extracellular matrix-receptor interactions and focal adhesion signaling. The ADME-related prognostic index correlates with immune cell infiltration and may serve as a therapeutic biomarker for CRC patients.

Breast cancer is the leading cause of death among women globally. Several genes have been found to be transcriptionally dysregulated in cancer, according to recent studies. TATA-box binding protein (TBP) and its two paralogs, TBPL1 and TBPL2, play roles in human transcription. The TBPL1 gene is implicated in colorectal carcinomas by suppressing the expression of miR-18a. However, its function in breast cancer remains undisclosed. TBPL1 is distantly related to TBP and possesses a 40% similarity with TBP's core domain. In the present study, we explored the potential role of the TBPL1 gene in transcriptome regulation by knocking out the TBPL1 gene through the CRISPR/Cas9 method. Following the knockout of the TBPL1 gene, we examined the gene transcription patterns and compared them to wild-type cell lines. We observed disparate signatures of upregulated and downregulated genes in wild-type and mutated conditions. Healthy breast MCF-12F, and T47D, SKBR3, and MDA-MB-231 breast cancer cell lines were assessed, as these cancer cells exhibit overexpression of the TBPL1 gene. Next-generation sequencing data revealed distinct marker genes regulated by the TBPL1 gene and their potential involvement in cell migration, proliferation, anti-apoptosis, and metastasis. Additionally, we also discovered novel lncRNAs implicated in the transcriptome analysis of the TBPL1 knocked-out gene. Our investigation indicated that this gene might affect varied stages of breast cancer cell lines' cellular properties, such as cell duplication, morphology, and growth. It might also contribute to tumor formation in more aggressive cell lines like MDA-MB-231 in vivo.

Transformer models have achieved remarkable success in natural language and vision tasks, but their application to gene expression analysis remains limited due to data sparsity, high dimensionality, and missing values. We present GexBERT, a transformer-based encoder-decoder framework for robust representation learning of gene expression data. GexBERT learns context-aware gene embeddings by pretraining on large-scale transcriptomic profiles with a masking and restoration objective that captures co-expression relationships among thousands of genes. We evaluate GexBERT across three critical tasks in cancer research: pan-cancer classification, cancer-specific survival prediction, and missing value imputation. GexBERT achieves state-of-the-art classification accuracy from limited gene subsets, improves survival prediction by restoring expression of prognostic anchor genes, and outperforms conventional imputation methods under high missingness. These findings demonstrate the utility of GexBERT as a scalable and effective tool for gene expression modeling, with translational potential in settings where gene coverage is limited or incomplete.

Ferroptosis and cuprotosis, two distinct mechanisms of programmed cell death, play key roles in colon cancer development. This study aimed to construct a prognostic model for predicting colon adenocarcinoma (COAD) prognosis based on the differential expression of cuproptosis-related ferroptosis genes (CFRGs).

There is an urgent need to better understand how information from circulating tumour DNA (ctDNA) can be integrated into routine care for patients with advanced solid cancer.

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer, in which TP53 mutation is uncommon in contrast to high-grade serous carcinoma, the predominant subtype. Therefore, the functional reactivation of p53 is an attractive therapeutic opportunity for this subtype of ovarian cancer. Nevertheless, the therapeutic potential of targeting MDM4, a representative negative regulator of p53, has not yet been reported. In the present study, we investigated the impact of CEP-1347, an MDM4 inhibitor with a known safety profile in humans, on p53 pathway activity and the growth of OCCC cells.

OIP5-AS1, a long noncoding RNA, promotes the proliferation, invasion, and migration of diverse cancer cell types such as cervical, breast, lung, and head and neck cancer. In this study, we showed that OIP5-AS1 is involved in the promotion of colorectal cancer (CRC) cell proliferation via repressing apoptosis.