Long-term follow-up studies regarding the safety of risk-reducing mastectomy (RRM) in terms of cancer risk and surgical complications among women with germline pathogenic variants (gPVs) in BRCA1 or BRCA2 (BRCA1/2) are scarce.

Colorectal cancer (CRC) is a prevalent and increasingly common malignancy that poses significant threats to patient survival and quality of life. This study investigates the role of ubiquitously expressed prefoldin-like chaperone (UXT) in regulating polyamine metabolism, particularly putrescine, and its impact on CRC progression. Through comprehensive bioinformatics analysis, UXT was identified as a key factor positively correlated with putrescine abundance in CRC cell lines. Clinical samples confirmed upregulation of UXT and its positive correlation with putrescine levels. Functional assays revealed that UXT knockdown reduced cell viability, migration, and invasion, while overexpression enhanced these phenotypes. Additionally, UXT knockdown decreased putrescine levels and increased the expression of ornithine decarboxylase antizymes (OAZ1, OAZ2, OAZ3), which negatively regulate polyamine synthesis. Conversely, UXT overexpression exhibited the opposite effects. In vivo experiments using a subcutaneous xenograft tumor model in nude mice showed that UXT overexpression enhanced tumor growth and putrescine levels, and UXT overexpression is associated with an increase in M2 macrophage markers, along with reduced M1-associated markers, while UXT knockdown inhibited these effects. These findings suggest that UXT contributes to CRC progression by regulating polyamine metabolism and macrophage polarization, demonstrating its potential as a therapeutic target to disrupt metabolic pathways essential for cancer cell survival and proliferation.

To evaluate the prognostic utility of the FIGO 2023 staging system with/without molecular classification vs. FIGO 2009 in endometrial cancer.

Thyroid carcinoma is characterized by significant heterogeneity and immune evasion, in which myeloid cells play a pivotal role in tumor microenvironment (TME) remodeling. However, the key regulatory genes and their underlying mechanisms are not yet fully elucidated.

BackgroundSERPINE1 has attracted considerable attention in tumor biology, but its clinical importance in head and neck squamous cell carcinoma (HNSCC) is not yet clear. We therefore examined whether SERPINE1 expression is related to survival in patients with HNSCC.MethodsWe searched three major databases (PubMed, EMBASE, and the Cochrane Library) and identified observational studies reporting survival outcomes in relation to SERPINE1 expression through November 11, 2024. From eligible reports we extracted data on progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS), and calculated pooled hazard ratios (HRs) using random-effects models.ResultsEleven studies including 733 individuals with HNSCC met the inclusion criteria. Across these cohorts, higher SERPINE1 expression was consistently linked with shorter OS (HR 2.81, P = 0.003) and shorter DFS (HR 1.57, P = 0.004). In contrast, no clear associations were observed for PFS or DSS (P ≥ 0.05).ConclusionCurrent evidence suggests that increased SERPINE1 expression is associated with an unfavorable prognosis in HNSCC, particularly for OS and DFS. Larger prospective studies are needed to confirm these findings and to determine how SERPINE1 assessment might be incorporated into risk stratification and treatment planning for patients with HNSCC.

MutL homolog 1 (MLH1) loss is a defining molecular feature of endometrial cancer (EC) and a principal driver of microsatellite instability (MSI). Ishikawa cells harbor intrinsic MLH1 promoter hypermethylation, resulting in reduced but not abolished MLH1 expression and placing these cells in a vulnerable, partially compromised mismatch repair state. This study explores the effects of MLH1 knockdown (MLH1-KD) on MSI, cellular functions, signaling pathways, and tumor growth in Ishikawa EC cells.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the immunohistochemical images shown in Fig. 1A on p. 1377, the 'DNMT3A' and 'DNMT3B' images for the 'BN' row of data contained an overlapping section, such that date which were intended to show the results from differently performed experiments had apparently been derived from the same original source. In addition, upon performing an independent analysis of the data in this paper in the Editorial Office, it came to light that the same data had been included for the Petri dish images in Fig. 3B on p. 1382 for the DMSO experiments with the T24 and EJ cell lines, albeit the EJ image had been rotated through 90°. The authors were contacted by the Editorial Office to offer an explanation for this apparent duplication of data within these figures; however, up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 35: 1375‑1384, 2016; DOI: 10.3892/or.2015.4492].

High mobility group box 3 (HMGB3) acts as an essential participator in fundamental biological processes, including transcriptional regulation, chromatin remodeling and DNA repair. HMGB3 is highly expressed and functionally essential during embryonic development, particularly in the hematopoietic and nervous systems, but it is significantly downregulated or silenced in most normal adult tissues. Its aberrant upregulation has been revealed in numerous human malignancies, such as leukemia, as well as breast, bladder, colorectal and gastric cancer, and its expression levels have been established to be closely associated with poor prognosis of specific patients. Accordingly, the present review systematically explores the central roles of HMGB3 in mediating resistance to cancer therapy. This review focuses on its multifaceted mechanisms of maintaining cancer stemness, enhancing DNA damage repair, modulating cell death pathways and remodeling the tumor microenvironment, thereby contributing to the resistance to chemotherapy, radiotherapy, targeted therapy and immunotherapy collectively. HMGB3 can be accepted as a key target in the development of highly promising therapeutic strategies, given its pivotal involvement in multidrug resistance, which may offer novel avenues for overcoming clinical treatment resistance and improving patient outcomes.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the paraffin‑embedded glioma tissue sections shown in Fig. 2A on p. 494, the Ki‑67/Grade III and DTX3L/Grade IV data panels contained an overlapping section, suggesting that these data panels were derived from the same original source where different experimental groups were reported. In addition, GAPDH control western blots featured in Figs. 1C and 4E were found to be strikingly similar, even though the experimental conditions reported for these figure parts were different. The authors have been contacted by the Editorial Office to offer an explanation for these apparent anomalies in the presentation of the data in their paper, and we are awaiting their response. Due to the fact that we have been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of these potential problems while the Editorial Office continues to investigate this matter further. [International Journal of Molecular Medicine 40: 491‑498, 2017; DOI: 10.3892/ijmm.2017.3023].

Chromodomain helicase DNA‑binding protein 4 (CHD4) is a core adenosine triphosphate (ATP)‑dependent chromatin‑remodeling factor of the nucleosome‑remodeling and deacetylase (NuRD) complex. It plays a crucial role in chromatin structure regulation, gene expression regulation, and DNA damage response. It has been demonstrated that CHD4 has context‑dependent functions in tumor development and progression. It can influence tumor progression via such mechanisms as regulating tumor‑related signaling pathways, maintaining the silencing of tumor suppressor genes, and promoting metabolic adaptation; it can also exert tumor‑suppressive effects in specific transcriptional regulatory environments. Additionally, during DNA damage response, CHD4 participates in chromatin remodeling at damage sites, in cell cycle recovery, and in repair pathway selection. It is also involved in the development of tumor treatment resistance through mechanisms that include regulation of DNA repair, cell cycle progression, drug efflux, the tumor immune microenvironment, and replication fork stability. It has also been shown that various non‑coding RNAs participate in the functional regulation of CHD4 by modulating its expression, localization, and protein stability. In summary, as a key node connecting chromatin regulation, genome stability, and tumor treatment response, CHD4 holds significant importance in tumor progression and treatment.

The global incidence of thyroid cancer (TC) has markedly increased in recent years, making it the most prevalent endocrine‑related cancer worldwide. TC primarily originates from follicular and parafollicular cells of the thyroid gland, and includes four main pathological types: Papillary TC (PTC), follicular TC, medullary TC (MTC) and anaplastic TC. Notably, characteristic oncogenes and tumor suppressor genes are associated with TC, which are considered targets for the development of treatment strategies. The rearranged during transfection (RET) gene serves a pivotal role in the development of TC, and mutations and fusions of this gene are closely associated with the onset of MTC and PTC. The structure of RET includes four cadherin‑like domains and 16 cysteine residues in its extracellular domain, which confer unique functionalities and contribute to its intracellular role. RET activation is a complex process involving multiple intracellular events, including calcium ion binding, glial cell line‑derived neurotrophic factor family ligand binding, and RET receptor aggregation, dimerization and autophosphorylation. The present study reviews the structure and function of the RET proto‑oncogene and its pathogenic roles in various TC subtypes.

RNA polymerase II (Pol II) is an essential eukaryotic enzyme that transcribes protein‑coding genes and various non‑coding RNAs. RNA polymerase II, I and III subunit L (POLR2L) is a highly conserved component shared by RNA polymerase subunits I, II, and III, which contributes to transcriptional regulation, enzymatic structural integrity, key cellular processes such as proliferation, differentiation, and stress responses. Recent research has shown that POLR2L is not merely a Pol II structural subunit but also plays key roles in disease progression, particularly cancer, where POLR2L dysregulation contributes to tumor growth, metastasis, and resistance to chemotherapy. Additionally, POLR2L is closely linked to major signaling pathways including the PI3K‑Akt, Wnt/β‑catenin, and TGF‑β pathways, highlighting the diverse roles played by POLR2L in cellular signaling. This review summarizes current knowledge on the structural and functional properties of POLR2L, its involvement in various diseases, and its potential as a therapeutic target. By outlining the diagnostic and therapeutic relevance of POLR2L, this review aims to provide a framework for understanding how POLR2L related research may inform transcriptional regulation and its impact on human health and disease.

Histone modification is an important mechanism of epigenetic regulation. New histone modifications play key roles in the regulation of gene expression and in the development and progression of various diseases. In addition to histone modifications, epigenetic regulation includes classic pathways such as DNA methylation, chromatin remodeling complexes and non‑coding RNAs, which interact with each other and jointly shape the occurrence and development of gastric cancer (GC). The present study systematically elaborated on the role of histone modification in GC and introduced several main types of histone modification, including acetylation, methylation, citrullination, ubiquitination and lactylation, focusing on histone lactylation modification and exploring its biochemical basis, interaction with other modifications and functions such as metabolic reprogramming, cell proliferation, migration and immune escape, covering non‑tumor and other cancer fields. On this basis, the specific application of histone modification (acetylation, methylation and other modifications) in GC is further explained and the effects of histone lactylation on metabolic reprogramming, proliferation, migration and immune escape of GC are analyzed in detail. Finally, the clinical significance of histone lactylation modifications in the diagnosis and prognosis of GC, biomarkers, therapeutic targets and drug resistance mechanisms provides a reference for an in‑depth understanding of the role of histone modifications, especially lactylation modifications, in the development of GC and clinical transformation applications.

Lung cancer is an aggressive malignancy associated with a rapid progression and poor prognosis, for which immunotherapy only exhibits modest efficacy in most patients. In lung cancer, high lactate is associated with a low immunotherapy response and shortened survival; however, causal lactylation‑related genes remain to be elucidated. In the present study, candidate genes were screened using Mendelian randomization (MR) analysis, with expression quantitative trait loci data and genome‑wide association study summary statistics used as analytical resources. A total of 46 lactylation‑related genes were included in the MR analysis, and multiple testing correction was performed using the false discovery rate (FDR) and Bonferroni methods to control the false‑positive risk. MR identified three core genes [platelet‑type phosphofructokinase; SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; and stathmin 1 (STMN1)]. Among these genes, only STMN1 was significantly associated with increased lung cancer risk (inverse variance weighting original P=0.005, FDR‑corrected P=0.014995, Bonferroni‑corrected P=0.014995, odds ratio=1.741, 95% confidence interval: 1.182‑2.564), with robust results confirmed by heterogeneity/pleiotropy/sensitivity analyses. Subsequently, transcriptomic analysis was conducted to assess STMN1 expression in lung cancer tissues and its association with patient survival. In vitro (cell proliferation, migration, invasion and apoptosis assays) and in vivo experiments (murine tumor models) were also conducted to explore the function of STMN1. STMN1 exhibited upregulation in lung cancer tissues, and was associated with a shorter survival, reduced antitumor immune cell infiltration and an immunosuppressive tumor microenvironment (TME) phenotype. STMN1 knockdown inhibited lung cancer malignancy both in vitro and in vivo, and modulated key markers, whereas its overexpression exhibited the opposite effects. Additionally, STMN1 promoted global histone lactylation and histone H3 lysine 18 lactylation in lung cancer cells, establishing a direct functional link between STMN1 and the lactylation pathway. In conclusion, STMN1 is a lactylation‑related causal oncogene in lung cancer, driving progression via malignant phenotypes, and its high expression is associated with an immunosuppressive TME that may synergistically facilitate tumor progression. Therefore, STMN1 may be considered a novel target for lung cancer therapy.

Objective To investigate the concordance of programmed death ligand-1 (PD-L1) expression between primary non-small cell lung cancer (NSCLC) and paired brain metastasis, analyze its relationship with clinicopathological characteristics, and evaluate the feasibility of using primary tumor PD-L1 status to predict brain metastasis status. Methods Thirty-two paired primary NSCLC and brain metastasis samples, pathologically diagnosed between January 1, 2017 and July 1, 2022, were collected. PD-L1 expression was detected by immunohistochemistry and interpreted using the Tumor Proportion Score (TPS), with cut-off values set at 1% and 50%. The Chi-square test was used to analyze the relationship between PD-L1 expression and clinicopathological features. Paired Chi-square and Kappa consistency tests were employed to assess the concordance of PD-L1 expression between primary and metastatic sites. Results PD-L1 expression showed no significant correlation with patient gender, age, treatment history, or histologic type. At the 1% cut-off, the overall PD-L1 expression showed moderate concordance between primary and metastatic sites (Kappa=0.624). Subgroup analysis revealed high concordance in untreated patients (Kappa=0.761, P=0.001), whereas the treated group showed weak concordance without statistical significance (Kappa=0.324, P=0.205). At the 50% cut-off, both the treatment group and the untreated group showed weak concordance without statistical significance. Although the chemotherapy subgroup showed perfect agreement (Kappa=1.000) at the 50% cut-off, the high-expression concordance rate was only 20.00%, indicating limited clinical reference value. Conclusion The strong concordance of PD-L1 expression in the untreated group patients supports the use of primary tumor PD-L1 status to guide clinical decision-making when brain metastasis tissue is unavailable. Treatment status (mainly including chemotherapy) may be an important factor affecting the consistency of high PD-L1 expression between primary NSCLC and brain metastasis.

Background. Diffuse brainstem tumors account for 10-20% of all brain tumors in children. These neoplasms are the leading cause of death in pediatric neuro-oncology. There are no effective treatments for this disease. Overall survival rarely exceeds 1.5-2 years.

Glioblastoma or grade IV glioma is characterized by extremely poor prognosis. Resistance to radio- / chemotherapy and recurrences are associated with tumor stem cells. Transmembrane protein CD133 is considered a potential marker of tumor stem cells. To overcome the limitations of detecting cellular CD133 by antibodies, potential of aptamers (nucleic acid-based molecular recognition elements) is being explored. To obtain reproducible results, it is necessary to study the interaction of fluorescent aptamers to CD133 with standard cell lines and cell cultures derived from patient tumors using various methods.

Bladder cancer (BCa) progression is closely linked to the immune microenvironment. However, the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood. This study aims to identify a key molecule and elucidate its mechanisms, providing a theoretical basis for identifying novel therapeutic targets.

ADP-ribosyltransferases (ARTs) regulate key processes in cancer, including DNA repair, transcription, immune responses, and treatment resistance. The clostridial toxin-like ADP-ribosyltransferase (ARTC) family and the diphtheria toxin-like ADP-ribosyltransferase (ARTD) family play a crucial role in genomic stability by modification of proteins either with mono(ADP-ribosyl)ation (MARylation) or poly(ADP-ribosyl)ation (PARylation). These ARTs are promising therapeutic targets and could serve as biomarkers in cancer management. This review explores the roles of these enzymes and current knowledge on specific inhibitors. A literature search was conducted in PubMed and Google Scholar to identify studies published between 1992 and 2025 on ADP-ribosyltransferases and their roles in cancer. Among ARTC family, ART1 and ART3 modulate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, influencing angiogenesis, tumor growth, and immune evasion via cluster of differentiation 8+ (CD8+) T-cell apoptosis. Within the ARTD family, poly(ADP-ribose)polymerase (PARP)1 and PARP2 are activated by DNA single-strand breaks and are clinically validated targets in cancers with homologous recombination deficiency, such as breast cancer susceptibility genes 1/2 (BRCA1/2)-mutated breast cancer. Their inhibition exemplifies synthetic lethality and has shown clinical efficacy. Four PARP inhibitors, olaparib, niraparib, rucaparib, are approved by the Food and Drug Administration (FDA) approved. Despite these advances, selective inhibitors for ARTs remain underexplored. Ongoing research focuses on overcoming PARP inhibitor resistance, improving biomarker-driven patient selection, and expanding therapeutic strategies that target ART-related pathways.

Long non-coding RNAs have been found to play a pivotal role in breast cancer, yet the majority of these lncRNAs remain to be thoroughly investigated. This study aimed to explore the role of differentially expressed long non-coding RNAs (lncRNAs) in breast cancer stemness and drug sensitivity.