Translational cancer research最新文献

Background: Gliomas are highly aggressive brain tumors with complex metabolic and molecular alterations. The role of glycolysis in glioma progression and its regulation by hypoxia remain poorly understood. This study investigated the function of glycogen phosphorylase L (PYGL) in glioma and its interaction with glycolytic pathways under hypoxic conditions.

Methods: Differential expression analysis was conducted using The Cancer Genome Atlas (TCGA) glioma and GSE67089 datasets, revealing significant changes in the expression of genes. A prognostic risk model incorporating PYGL was built by univariate and multivariate Cox regression analyses. The impacts of PYGL on glioma cell proliferation, glycolysis, apoptosis, and metabolic activities were evaluated by in vitro assays. Additionally, the influences of hypoxia and hypoxia-inducible factor 1-alpha (HIF1α) on PYGL expression were evaluated.

Results: Our prognostic prediction model showed a C-index of 0.76 [95% confidence interval (CI): 0.70-0.82], indicating a good predictive accuracy of the model. In addition, genetic predictors included in the nomogram included PYGL, HIF1α, and other genes associated with the glycolytic pathway. Differential expression analysis identified PYGL as a key gene associated with glioma survival. PYGL expression was significantly upregulated in glioma cells. PYGL knockdown inhibited cell invasion, proliferation, migration, and colony formation and enhanced apoptosis via modulation of Bcl-2, caspase-3, and Bax. Glycolysis was impaired in PYGL-knockdown cells, as indicated by increased glycogen levels and a reduced extracellular acidification rate (ECAR), adenosine triphosphate (ATP) levels, lactate levels, and PKM2 and LDHA expression. PYGL overexpression promoted glycolysis and cell viability, which was counteracted by 2-deoxy-D-glucose (2-DG). Hypoxia-induced PYGL expression was regulated by HIF1α, underscoring the interplay between the hypoxia and glycolysis pathways.

Conclusions: PYGL is a crucial regulator of glycolysis in gliomas and contributes to tumor progression under hypoxic conditions. Targeting PYGL and its associated metabolic pathways may offer new therapeutic strategies for glioma treatment.

Background: With the advancement of various auxiliary examination techniques, the detection rate of stage I gastric cancer has gradually increased, and its clinical first-choice treatment is surgery. Although patients with stage I gastric cancer generally have a good postoperative survival rate, there is still a certain probability of recurrence. Given the large number of gastric cancer cases, there is a vast population of patients with stage I disease. We are aiming to identify the risk factors for postoperative recurrence of stage I gastric cancer and to establish a reliable predictive model to assess the risk of recurrence in the population for clinical practice.

Methods: In this retrospective cohort study, we utilized the Surveillance, Epidemiology, and End Results (SEER) database to investigate predictive factors for recurrence among stage I gastric cancer patients who underwent curative gastrectomy between 2000 and 2018. The cohort was divided into training and validation sets for the development and validation of a nomogram. Prognostic factors were evaluated through univariate and multivariate Cox regression analyses. Significant variables identified by the concordance index (C-index) and calibration plots were used to construct nomograms predicting the probability of 5- and 10-year recurrence.

Results: Risk factors for recurrence included sex, age, race, histology, tumor size, American Joint Committee on Cancer Tumor (AJCC T) and primary site, which were used to construct the nomogram. The C-index for both the training and validation cohorts indicated that the nomogram possessed good calibration and discrimination abilities in predicting the probability of 5- and 10-year recurrence after curative surgery for stage I gastric cancer.

Conclusions: This study established a reliable predictive model for recurrence following curative gastrectomy in stage I gastric cancer based on a population cohort. The findings of this study have the potential to significantly impact clinical practice by providing clinicians with tools for personalized risk assessment and for making informed treatment decisions.

Background: Glioma characterized by the high degree of drug resistance and the poor prognosis is the most common primary malignant tumors of the brain. And miRNA is involved in a variety of biological behaviors of tumors, enhancing or inhibiting the occurrence and development of tumors. Therefore, the present study aims to explore whether miR-155-5p can regulate autophagy and apoptosis of glioma through RICTOR.

Methods: The significantly differential gene miR-155-5p was identified from the Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo) databases GSE165937 and GSE138764 using bioinformatics analysis, and its expression was validated by quantitative real-time polymerase chain reaction (qRT-PCR). The putative target genes of miR-155-5p were predicted through interrogation of relevant databases, followed by identification of key target genes. Subsequently, core target genes were selected for functional enrichment analysis. The U87MG cell line was utilized as the experimental model and divided into Negative Control1 (NC1) group, Mimic group, Negative Control2 (NC2) group, Inhibitor group, and NC + 3-methyladenine (3-MA) group. The expression levels of miR-155-5p, RICTOR, P62, LC-3, Bax, Bcl-2, and Caspase-3 were assessed using qRT-PCR, cellular fluorescence imaging, and Western blotting; while apoptosis in the U87MG cell line was evaluated via flow cytometry.

Results: The results showed that miR-155-5P was highly expressed in glioma cells, which could inhibit the expression of Bax, Caspase-3, LCII/LCI and Beclin-1, and increase the expression of Bcl2 and P62. Flow cytometry and cell fluorescence were used to verify the above results. Moreover, when U87MG cells treated with miR-155-5p inhibitor were inhibited by 3-MA, the results showed that miR-155-5p enhanced the anti-apoptotic ability of U87MG cells by regulating autophagy. In addition, the bioinformatics results show that miR-155-5p survival prognosis in glioma into a strong negative correlation, while the survival prognosis of RICTOR in glioma showed a strong positive correlation. The core target genes Kyoto Encyclopedia of Genes and Genomes (KEGG) mainly occurred in PI3K-AKT signaling pathway; in addition, qRT-PCR and Western blot confirmed the regulatory effect of miR-155-5P on RICTOR.

Conclusions: MiR-155-5p regulates autophagy and apoptosis-related proteins in glioma cells through RICTOR, affecting the occurrence and development of glioma.

Background and objective: The occurrence and development of tumors in human tissues widely depend on their surrounding environment, known as the tumor microenvironment (TME), which comprises various cells, molecules, and blood vessels. Through modifications, organization, and integration, these elements serve as potential therapeutic targets in anti-cancer therapy, supporting and promoting the proliferation, invasion, and metabolism of tumor cells. Cytokines within TME are responsible for immune cell activation, proliferation, and differentiation, thereby influencing the tumor's behavior. This article reviews the use of cytokines in tumor immunotherapy and combs the network signals that cytokines mediate in the development of malignancies.

Methods: A literature search of international sources was carried out on the PubMed and Web of Science databases, using main keywords such as "tumor immunotherapy", "cytokines", "chemokines", "tumor microenvironment", "recombinant cytokine engineering", and "tumor necrosis factor superfamily".

Key content and findings: The review provides a thorough summary of the functions of tumor necrosis factor superfamilies, chemokines, and interleukins within the TME as well as their therapeutic uses. Their potential as novel targets for tumor treatment is also evaluated. Furthermore, this paper focuses on various feasible strategies for recombinant cytokines reported in recent years, especially the cytokine engineering methods for targeting tumors. Ultimately, this paper contributes to an enhanced understanding among researchers of the mechanisms underlying the impact of the TME on disease development, thereby laying a solid foundation for the future development of new tumor therapies based on cytokines within the TME.

Conclusions: Cytokine immunotherapy holds promise on antitumor therapy. It is anticipated that the effectiveness of tumor treatment and the quality of life for tumor patients will continue to improve with ongoing research and development in this field.

Background and objective: The bone marrow microenvironment is closely related to normal hematopoiesis and hematologic tumors. Adipocytes are an important part of the bone marrow microenvironment, in which they can release free fatty acids (FFAs) through lipolysis and secrete adipocytokines, etc., and participate in normal hematopoiesis, which is closely related to the occurrence and treatment of hematological tumors. In this review, we aim to discuss how bone marrow adipocytes (BMAs) can influence the proliferation, apoptosis, and chemotherapy resistance of cancer cells by reprogramming lipid metabolism and the secretion of various adipocytokines.

Methods: Studies from 2000 to July 2024 were reviewed from PubMed, Springer Link, and the Web of Science using the keywords bone marrow microenvironment, adipocytes, lipid metabolism, adipocytokines, hematological tumor, cancer, and their combinations. Unreliable articles such as those that are old and have a low impact factor are excluded, and there is no restriction on language.

Key content and findings: Adipocytes can regulate the proliferation and differentiation of hematopoietic stem cells (HSCs) by secreting inflammatory factors and adipocytokines to maintain hematopoietic homeostasis. Adipocytes can also stimulate and accelerate the occurrence and progression of hematological tumors by secreting adipocytokines and mediating the reprogramming of lipid metabolism. Moreover, abundant adipocytes in bone marrow can protect tumor cells by physically blocking and/or secreting cytokines, leading to chemotherapy resistance.

Conclusions: Therefore, the targeted inhibition of related lipid metabolism pathways and adipocytokines might be a potential therapeutic target for hematological tumors, which would be helpful to inhibit tumor growth and correct chemotherapy resistance.

[This retracts the article DOI: 10.21037/tcr.2020.01.27.].

Background: Transmembrane p24 trafficking protein 9 (TMED9) belongs to the TMED family, and its overexpression frequently induces cancer. Studies have demonstrated the association between the overexpression of TMED9 and cancer development and proliferative migration in cancers such as ovarian cancer, hepatocellular carcinoma, and breast cancer. However, there has been no study investigating the clinical value, biological function, and anti-tumor immune effects of TMED9 from a pan-cancer perspective. The aim of this study is to evaluate the prognostic value and anti-tumor immunity role of TMED9 across pan-cancers.

Methods: We utilized R language along with The Cancer Genome Atlas (TCGA), UCSC Xena (University of California, Santa Cruz Xena Browser), Human Protein Atlas (HPA), and other datasets to investigate TMED9 expression in various tumors. The association between high TMED9 expression and clinical prognosis and patient survival was examined using the Kaplan-Meier method, log-rank test, as well as univariate and multivariate Cox regression analyses. Tumor Immune Estimation Resource 2.0 (TIMER2.0) and various algorithms were employed to explore the relationship between TMED9 and the tumor microenvironment (TME). Additionally, the biological function of TMED9 in cancer was investigated through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analyses.

Results: TMED9 was over-expressed in the majority of cancers. Patients exhibiting elevated TMED9 expression typically experienced diminished survival rates and unfavorable clinical outcomes. TMED9 played a role as a mediator in the aggressive phenotype of numerous tumors, actively engaging in various biological and signaling pathways linked to cancer development. TMED9 demonstrated the capacity to modulate the anti-tumor immune response in pan-cancer patients, exerting its influence on the infiltration levels of immune cells and cancer-associated fibroblasts (CAFs).

Conclusions: TMED9 serves as a novel "cancer indicator" and "clinical prognostic marker", capable of reshaping the TME, impacting the immunotherapeutic response, and guiding precise treatments for cancers to a certain extent.

Background: Oral squamous cell carcinoma (OSCC) is one of the most malignant tumors in the oral and maxillofacial region, with a poor prognosis. Previous studies have shown that long non-coding RNAs (lncRNAs) play a crucial role in tumor development by regulating the biological behavior of various cancer cells. The aim of this study is to explore the role and potential mechanisms of lncRNA PRKCA-AS1 in OSCC.

Methods: Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression levels of lncRNA PRKCA-AS1 in OSCC tissues and cell lines. Cell proliferation, migration and invasion were conducted to assess the biological functions of OSCC cell lines.

Results: The expression of lncRNA PRKCA-AS1 in OSCC tissues was higher compared to that of adjacent non-cancerous tissues, and its expression level was associated with the depth of tumor infiltration, lymph node metastasis, and tumor node metastasis (TNM) staging. Compared to the control group of normal human oral keratinocytes (HOK), the expression of lncRNA PRKCA-AS1 was also elevated in OSCC cell lines. Knockdown of lncRNA PRKCA-AS1 significantly affected the proliferation, migration, and invasion ability of OSCC cells. However, when lncRNA PRKCA-AS1 was further overexpressed, changes in cell proliferation and migration ability did not show statistical differences.

Conclusions: LncRNA PRKCA-AS1 is highly expressed in OSCC, and its expression level is positively correlated with the depth of tumor infiltration, lymph node metastasis, and TNM staging. LncRNA PRKCA-AS1 is involved in regulating the proliferation, migration, and invasion of OSCC cells.