Oncology reports最新文献

Gastric cancer is a malignancy with a high incidence and poor prognosis. The identification of novel molecular markers and elucidation of their underlying mechanisms may provide new avenues for improving therapeutic strategies. The present study analyzed the association between GPR176 expression and clinicopathological features using The Cancer Genome Atlas‑Stomach Adenocarcinoma and GSE66254 datasets, and further validated the findings in patients from The First Affiliated Hospital of Guangxi Medical University (Nanning, China). The migratory and invasive abilities of gastric cancer cells were assessed using Transwell and wound‑healing assays. Western blotting was carried out to evaluate the effects of GPR176 on the PI3K/AKT/mTOR signaling pathway. In vivo tumorigenesis assays in nude mice were carried out to confirm the role of GPR176 in tumor progression. Analysis revealed that GPR176 expression was significantly elevated in gastric cancer tissues and associated with unfavorable patient outcomes. Silencing GPR176 markedly suppressed the migration and invasion of gastric cancer cells, accompanied by inhibition of the PI3K/AKT/mTOR and EMT signaling pathways. These inhibitory effects were prevented by the overexpression of PIP5K1A. In line with the in vitro results, experiments with nude mice demonstrated that GPR176 knockdown impeded tumor growth, whereas its overexpression enhanced tumorigenicity. Furthermore, GPR176 suppression significantly attenuated EMT and PI3K/AKT/mTOR signaling in vivo, while GPR176 overexpression led to activation of these pathways. In summary, the present study identifies GPR176 as a novel prognostic biomarker in gastric cancer. Mechanistically, GPR176 promotes EMT and tumor progression, at least in part, through activation of the PI3K/AKT/mTOR signaling pathway.

Breast cancer is the most common cancer in the female population worldwide. The present review examines the biology of breast cancer, with a focus on the interplay between tumor‑infiltrating lymphocytes (TILs) and microRNAs (miRNAs or miRs). TILs, which reflect the immune system activity in combating tumors, are associated with more favorable prognoses and positive response to therapies. Elevated levels of TILs characterize lymphocyte‑predominant breast cancers (LPBCs), which are associated with higher therapeutic response rates in triple‑negative breast cancer, a type of LPBC. Defining the threshold for LPBCs presents a challenge: TIL levels ≥50% are associated with short‑term pathological complete response as well as long‑term overall and disease‑free survival; however, this percentage is not often achieved in clinical practice. Conversely, a lower threshold of 30% lymphocyte infiltration can predict favorable prognosis for anticancer therapy and allows for the identification of a broader range of patients. The tumor inflammatory landscape is regulated by miRNAs, particularly miR‑155. Elevated levels of miR‑155 are associated with the presence of TILs and a favorable inflammatory profile, leading to a tumor‑inflamed microenvironment. Moreover, miR‑155 is associated with various antitumoral immune cells, including CD8⁺ T cells and M1 macrophages, but negatively associated with pro‑tumoral regulatory T cells and M2 macrophages. Overexpression of miR‑155 results in an increase in the levels of the C‑X‑C chemokine ligands, constituted by two conserved cysteines separated by a different amino acid which bind to the same chemokine receptor CXC chemokine receptor 3. These results in activation of T cells a process that involves the inhibition of suppressor of cytokine signaling 1 and an elevated ratio of phosphorylated STAT1/STAT3. Additionally, miR‑155 affects key signaling pathways, including the PI3K/AKT and IL‑6/STAT3 pathways, and increases sensitivity to immune checkpoint blockade therapy. In clinical samples from patients with BC, serum levels of miR‑155 align with both tumor miR‑155 levels and the immune status of the tumor. The present review emphasizes the importance of understanding the dynamics between TILs and miRNAs to identify new prognostic and predictive biomarkers, proposing a more integrated and personalized approach in the management of BC.

Glioblastoma remains a lethal malignancy with limited therapeutic advancements. Emerging evidence implicates cell cycle dysregulation in glioma pathogenesis, yet the mechanistic role of cyclin‑dependent kinase 1 (CDK1) remains underexplored. The present study systematically evaluated the clinical relevance and functional impact of CDK1 in glioma progression through multi‑modal experimental approaches. CDK1 expression was analyzed using public datasets and then verified by western blotting using patient tissue samples (n=37) from the Second Hospital of Hebei Medical University (Shijiazhuang, China). Survival analysis was performed using Chinese Glioma Genome Atlas and The Cancer Genome Atlas datasets, alongside multivariate Cox regression to evaluate prognostic independence. Functional assays, including small interfering RNA‑mediated CDK1 knockdown, were conducted in glioma cell lines to assess proliferation (Cell Counting Kit‑8 and EdU), migration/invasion (Transwell), apoptosis (acridine orange/ethidium bromide staining and flow cytometry) and radiosensitivity (γ‑H2AX foci quantification post‑irradiation). The expression levels of downstream cell cycle regulators were quantified via quantitative PCR. The results indicated that CDK1 was significantly upregulated in glioma tissues compared with normal controls, with expression levels escalating with tumor grade. High CDK1 expression correlated with a reduced overall survival and served as an independent prognostic marker. CDK1 knockdown attenuated glioma cell proliferation, migration and invasion, while enhancing apoptosis and radiosensitivity. Mechanistically, CDK1 knockdown downregulated cell cycle regulators proliferating cell nuclear antigen, minichromosome maintenance complex component 2‑4 (MCM2‑4), MCM6, polo‑like kinase 1, TTK protein kinase and mitotic arrest deficient 2 like 1, implicating mitotic dysregulation as a central pathway. The present study established CDK1 as a master regulator of glioma progression through coordinated control of proliferation, DNA repair and metastatic potential. The robust association between CDK1 expression, tumor grade and survival, coupled with functional validation across complementary assays, positions CDK1 inhibition as a promising therapeutic strategy. The mechanistic elucidation of its cell cycle network provides a novel framework for targeting glioma‑specific therapeutic targets.

Following the publication of the above article, the authors contacted the Editorial Office to explain that they had made inadvertent errors in compiling a couple of the figures in the above paper; first, regarding the immunohistochemical images shown in Fig. 2D on p. 5, the data panel shown correctly for the 'LC3/TPL+DDP' experiment contained an overlapping section with the 'LC3/TPL' data panel in the same figure part (the latter of which had been incorporated into this figure incorrectly). Secondly, the β‑actin bands correctly shown in Fig. 3D on p. 6 had incorrectly been included to represent the JAK2 western blot data in Fig. 4F on p. 7. However, the authors were able to re‑examine their original data, and realized how these errors had occurred. The revised and corrected versions of Figs. 2 and 4, now showing the correct data for the 'LC3/TPL' experiment in Fig. 2D and the JAK2 western blot data in Fig. 4F, are shown on the next two pages. Note that the errors made with the assembly of the data in these figures did not affect the overall conclusions reported in the paper. The authors apologize to the Editor of Oncology Reports and to the readership for any inconvenience caused. [Oncology Reports 45: 69, 2021; DOI: 10.3892/or.2021.8020]

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are among the most frequent oncogenic drivers in cancer, particularly in non‑small cell lung cancer (NSCLC). KRAS was previously considered an 'undruggable' target due to the protein's smooth molecular surface and the absence of obvious drug binding sites. However, the development of selective KRAS G12C inhibitors, such as sotorasib and adagrasib, together with progress in immunotherapy, have demonstrated potential clinical activity. Further understanding of the complex signaling networks driven by KRAS has revealed new opportunities to target this pathway directly or through rational combination strategies. The present review explored KRAS‑targeted therapies and immunotherapies, including limitations, resistance mechanisms and the efficacy of combination regimens. Although there has been notable progress, concerns regarding optimal therapy combinations, resistance management and early treatment strategies remain. The present review demonstrated the need for continued research to address these challenges and improve outcomes for patients with KRAS‑mutated NSCLC.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric data shown in Fig. 3C, the immunohistochemical data shown in Fig. 4B and the western blots in Fig. 5B had already been submitted to, or were published in, articles in other journals that featured some of the same authors; moreover, some of these data subsequently appeared in different articles in other journals that were not connected with either this research group or this research topic. Upon investigating these issues further in the Editorial Office, it was noted that, concerning Figs. 3‑5 and as far as those papers sharing some of the same authors was concerned, the cases of data sharing weren't necessarily as simple as the data merely being duplicated. Given the sharing of these contentious data across a number of different journals, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 32: 1571‑1577, 2024; DOI: 10.3892/or.2014.3386].

Colorectal cancer (CRC) is the third most common cancer globally and the second leading cause of cancer‑related mortalities. Surgery‑centered multimodal therapy remains the cornerstone of care, yet outcomes are poor in advanced or drug‑resistant disease. The tumor immune microenvironment (TIME), a network of immune cells, cytokines and stromal elements, shapes antitumor immunity and can either restrain or encourage tumor growth. Specific immune cells within the TIME influence CRC biology, while immune‑checkpoint blockade has delivered notable benefits, especially in microsatellite instability‑high tumors. The present review discusses the principal immune cell populations in the CRC TIME, outlines their mechanisms of action and discusses emerging cell‑based immunotherapies that may guide future precision treatment.

Hepatocellular carcinoma (HCC) represents the most common form of primary liver cancer and is characterized by a significant rate of recurrence. However, there is still a lack of effective therapeutic methods. Accumulating evidence has highlighted the importance of homeobox containing 1 (HMBOX1) in tumorigenesis. However, the relationship between HMBOX1 expression and HCC remains unclear. In the present study, through the analysis of public databases and staining analysis of tissue microarrays, it was found that compared with normal tissues, HMBOX1 was significantly downregulated in tumor tissues. Furthermore, through analyses such as Cell Counting Kit‑8 assay, wound healing assay and colony formation, it was found that overexpression of HMBOX1 could inhibit cell proliferation and migration, while silencing of HMBOX1 promoted tumor biological characteristics in HCC cell lines. The molecular biological mechanism was explored by using proteomics combined with bioinformatics analysis and western blotting. Mechanistically, AKT1 was identified as a downstream effector of HMBOX1, and protein tyrosine phosphatase non‑receptor type 1 (PTPN1) signaling might mediate the regulation of AKT1 by HMBOX1. In vivo tumor‑bearing experiments also verified the function of the HMBOX1/PTPN1/AKT1 pathway in HCC development. Taken together, the present findings revealed a new HMBOX1/PTPN1/AKT1 axis that inhibits tumor progression and provides new candidate therapy targets for HCC.

Bone sarcomas remain lethal despite multimodal therapy, primarily because the mineralized, immunosuppressive tumor microenvironment (TME) promotes chemo‑ and immune‑resistance. Integrating single‑cell and spatial omics across osteosarcoma, Ewing sarcoma and chondrosarcoma delineates subtype‑specific TME archetypes dominated by M2 macrophages, exhausted T cells and a stiff extracellular matrix. Mechanistic dissection reveals tractable vulnerabilities, myeloid reprogramming, extracellular matrix modulation and metabolic and epigenetic checkpoints, that can be targeted with bone‑selective delivery systems and biomarker‑driven combination trials to convert therapeutic failure into durable remission. Therefore, the aim of the present review is to synthesize the latest single‑cell, spatial and functional data to map bone‑sarcoma TME heterogeneity, dissect resistance mechanisms and propose integrated, biomarker‑guided therapeutic strategies that can be translated into treatments.

The tumor microenvironment (TME) of epidermal growth factor receptor (EGFR)‑mutant non‑small cell lung cancer (NSCLC) exhibits notable immunosuppressive properties. EGFR tyrosine kinase inhibitors (EGFR‑TKIs) induce dynamic remodeling of the TME. By boosting the infiltration of immune cells such as T cells and dendritic cells and decreasing immunosuppressive elements such as tumor‑associated macrophages and regulatory T cells, short‑term TKI treatment can effectively enhance antitumor immunity. However, the TME changes to an immunosuppressive state marked by PD‑L1 upregulation and immune escape with continued therapy and the emergence of resistance. This creates a transient immunotherapy window period during EGFR‑TKI treatment, when immune checkpoint inhibitors may achieve optimal efficacy. It is essential to identify and take advantage of this window in order to enhance treatment results. The present review highlights the importance of understanding TME dynamics in EGFR‑mutant NSCLC to optimize combination strategies and guide future therapeutic development.