Discover. Oncology最新文献

Introduction/background: The specific role of efferocytosis-related long noncoding RNAs (ERLncRNAs) in Clear Cell Renal Cell Carcinoma (ccRCC) has not been thoroughly examined. This study aims to identify and validate a signature of ERLncRNAs for prognostic prediction and characterization of the immune landscape in individuals with ccRCC.

Materials and methods: Analysis of ccRCC samples was conducted by utilizing clinical and RNA sequencing information obtained from The Cancer Genome Atlas (TCGA). Pearson correlation analysis was utilized to identify lncRNAs associated with efferocytosis, which was then used to create a new prognostic model through univariate Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and stepwise multivariate Cox analysis. In order to investigate the biological significance, we performed a functional enrichment analysis to assess how well the model predicts outcomes. Differences in the immune landscape were observed through a comparison of immune cell infiltration, tumor mutational burden (TMB), and tumor microenvironment (TME) characteristics. Following this, drug sensitivity analysis was conducted.

Results: This led to the identification of a unique signature consisting of seven ERLncRNAs (LINC01615, RUNX3-AS1, FOXD2-AS1, AC002070.1, LINC02747, LINC00944, and AC092296.1). Model performance was measured by Kaplan-Meier curves and receiver operating characteristic (ROC) curves. The nomogram and C-index provided additional validation of the strong correlation between the risk signature and clinical decision-making.

Conclusion: On the whole, our innovative signature exhibits potential for prognostic prediction and assessment of immunotherapeutic response in patients with ccRCC.

Purpose: Colorectal cancer (CRC) is among the most common malignant tumors worldwide, posing a significant threat to human health. Most patients with CRC are refractory to existing treatment regimens, such as immune checkpoint blockades (ICBs), yielding unsatisfactory outcomes. This study aimed to explore the effect and mechanism of a natural product, indole-3-carbinol (I3C), in CRC pathogenesis and immunotherapy.

Methods: A series of in vitro experiments, such as the cell counting kit-8 and wound healing assays, were used to assess the proliferative, colony-formating and migratory capacity of human CRC cells after I3C treatment. In vivo experiment, xenograft growth assay was conducted to verify the effect of I3C on CRC. Hematoxylin-eosin (HE) staining was utilized to evaluated the toxic effect of I3C. Immunohistochemical staining was used to detect CD8⁺ T cell infiltration. Subcutaneous CRC models constructed in immunocompetent mice were used to test the effects of I3C treatment in combination with PD1ab therapy. The Human Protein Atlas (HPA) database, cell transfection, and quantitative real-time polymerase chain reaction (RT-qPCR) experiments were used to explore the mechanism of I3C in CRC.

Results: I3C significantly inhibited CRC cell proliferation, colony formation, and migration capacity in vitro and in vivo. The result of HE staining indicated that I3C exert no significant toxic effect on heart, liver and kidney. HPA data analysis and RT-qPCR results demonstrated that PTEN expression was lower in CRC tissues than in normal tissues or cells. Besides, I3C exerted antitumor activity and promoted CD8⁺ T cell infiltration by upregulating PTEN expression. Consequently, I3C, in conjunction with PD1ab therapy, synergistically enhanced the antitumor effect on CRC in immunocompetent mice.

Conclusions: These findings suggested that by upregulating PTEN expression, the natural product I3C strongly prevented tumor progression and exerted no systematic toxicity in the major organs such as heart, kidney and liver. Furthermore, I3C significantly enhanced PD1ab therapeutic effect in CRC, highlighting its role as a candidate preventive or therapeutic compound for CRC therapy, especially in combination with PD1ab therapy. Further clinical trial should be conducted in the future.

Osteosarcoma, the most common primary bone malignancy, poses significant management challenges due to its aggressiveness and metastatic potential. This study investigates the role of anoikis-related genes, particularly phospholipase C beta 4 (PLCB4), as a prognostic biomarker in osteosarcoma. We analyzed transcriptome data from the TARGET and GSE21257 cohorts using bioinformatics tools, identifying 15 significant genes, with PLCB4 as a key marker linked to decreased survival. Our findings indicate a negative correlation between PLCB4 and immune microenvironment scores and checkpoint molecules, suggesting its impact on immunotherapy responses. Drug sensitivity analyses revealed that high PLCB4 expression correlates with lower IC50 values for several chemotherapeutic agents. In vitro experiments showed that silencing PLCB4 inhibited cell proliferation and reduced PD-L1 expression. This study underscores the critical role of PLCB4 in osteosarcoma progression and its potential as a therapeutic target, offering insights into the molecular mechanisms of osteosarcoma biology and improving prognostic accuracy and treatment strategies.

Background: Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (Ph-negative BCP-ALL) accounts for a significant portion of adult cases. Blinatumomab, a bispecific T-cell engager, has shown efficacy in relapsed or refractory BCP-ALL, but its role in induction therapy with reduced-dose chemotherapy is being explored.

Methods: In this retrospective study, 35 newly diagnosed Ph-negative BCP-ALL patients received reduced-dose chemotherapy followed by two weeks of blinatumomab (RDC-Blinatumomab-2W) as part of our previous clinical trial. These patients were compared with a propensity score-matched historical control group of 35 patients treated with the hyper-CVAD regimen. The primary endpoint was composite complete remission (CRc); secondary endpoints included minimal residual disease (MRD) negativity, adverse events, and survival outcomes.

Results: After matching, both groups had 17 patients (49%) with poor-risk genetic aberrations. The RDC-Blinatumomab-2W group achieved higher CRc rates compared to controls (94% vs. 63%, p = 0.0074) and greater MRD negativity (86% vs. 43%, p = 0.0015). They experienced fewer Grade 3-4 thrombocytopenia cases (62% vs. 89%, p = 0.012), fewer serious infections (23% vs. 54%, p = 0.019), and higher 1-year overall survival rates (97.1% vs. 58.9%, p < 0.001). The 1-year progression-free survival was also superior in the RDC-Blinatumomab-2W group (82.2% vs. 44.6%, p = 0.002).

Conclusion: Reduced-dose chemotherapy followed by blinatumomab improves remission rates, MRD negativity, and survival while reducing adverse events in newly diagnosed Ph-negative BCP-ALL patients compared to hyper-CVAD. This regimen offers a safer and more effective induction therapy option, warranting further investigation in larger trials.

Clinicaltrials:

Gov identifier: NCT05557110; registered on September 8, 2022.

Pancreatic cancer ranks as the fourth most common cause of cancer-related fatalities globally, with a notably low 5-year relative survival rate. We need to immediately develop fast, dependable, and noninvasive diagnostic techniques that can accurately identify pancreatic cancer at an early stage. The research project created a straightforward but effective method for detecting and increasing the amount of tumor cells that could bind to polystyrene (PS) well plates. To significantly improve the adhesion of the pancreatic cancer cell line PANC-1 on PS well plates, a 5-min exposure to high-power oxygen plasma was implemented. This treatment caused a significant increase in surface energy and roughness. Surface characterization was assessed by utilizing an atomic force microscope and X-ray photoelectron spectroscopy. Water contact angle measurement is used to assess the level of wettability present on the treated surface. To determine how well the circulatory tumor cells (CTCs) model adheres to a plasma-treated surface (PTS), appropriate amounts of mCherry-labeled PANC-1 cells are mixed into a sample of blood cells to mimic clinical conditions. After applying plasma treatment, the experiment achieved a 96% success rate in binding at 2 h, specifically for the PANC-1 cell type. Moreover, the platform demonstrated a considerable ability to attach to cancerous cells compared to non-cancerous cells found in blood. To summarize, this study has shown that non-thermal plasma treatment could be a novel and efficient method for the better adhesion of pancreatic cancer cells, with the benefits of being cost-effective and quick. It is necessary for additional research to be conducted to confirm the clinical efficacy of the method.

Background: Lung cancer is the second most prevalent malignancy among males and females and the leading cause of cancer deaths. Due to its high mortality, identification of novel therapeutic options is of critical value. Regulatory T cells and their associated transcripts are among possible targets for design of targeted therapies.

Methods: Here, we assessed expression of lncRNAs that are possibly involved in Treg lineage commitment and their plasticity in lung tumor tissues (TT) and normal tissues adjacent to the tumor (NTAT).

Results: We found up-regulation of TH2-LCR, IFNG-AS1, and MAFTRR in TT samples compared with NTATs. The highest difference in the expression between two sets of samples belonged to MAFTRR with expression ratio (95% CI) of 6.48 (2.67-15.7). TH2-LCR ranked second in this list with expression ratio (95% CI) of 5.23 (1.92-14.24). Finally, IFNG-AS1 was up-regulated in TT samples compared with NTATs with expression ratio (95% CI) of 3.3 (1.56-6.95). Then, the suitability of MAFTRR, TH2-LCR and IFNG-AS1 in the separation of TT samples from NTATs was assessed through plotting sensitivity values against 1-specifiicity values in ROC curves. The obtained AUC values were 0.74, 0.71 and 0.7, respectively.

Conclusion: In brief, we demonstrated dysregulation of three Treg-related lncRNAs in lung cancer tissues and suggested them as possible candidates for biomarker discovery investigations.

Background: Although relevant research has unveiled the intricate connections between immune cells and the occurrence and prognosis of esophageal cancer (EC), the specific impact of immune cell phenotypes on EC remains unclear.

Methods: We employed bidirectional two-sample Mendelian Randomization (MR) analysis to explore the causal relationship between immune cell phenotypes and EC. The summary data for immune cell phenotypes and EC are both sourced from the GWAS (Genome-Wide Association Study) database. Sensitivity analysis was conducted on the results, utilizing a combination of MR-Egger and MR-Presso to assess horizontal pleiotropy, employing Cochran's Q test to evaluate heterogeneity.

Results: We identified 24 immunophenotypes with potential causal relationships to EC. Our results are presented based on the panel results from flow cytometry detection, categorized into B-cell panel, TBNK panel, cDC panel, Maturation stages of T-cell panel, Monocyte panel, and Myeloid cell panel. In the reverse MR analysis, we found a potential negative correlation between EC and IgD + CD38dim B cell Absolute Count (OR = 0.94, 95% CI, 0.88-0.99, P = 0.023).

Conclusion: This study has unveiled the causal relationship between immune cell phenotypes and EC, providing new insights for the exploration of immunotherapy targets in subsequent EC research and for the assessment of EC prognosis.

SOX2 is one of the members of the SOX transcription factor family, which is believed to be an important transcription factor that plays a role in embryonic development, maintenance of stem cells, cancer progression, and resistance to cancer treatment. There is increasing evidence suggesting that SOX2 is crucial for the initiation, progression, invasion, metastasis, and treatment resistance of prostate cancer, therefore understanding the mechanism of SOX2 in prostate cancer can provide better targets for the treatment of prostate cancer. This article reviews the structural domains, normal physiological functions, and role in prostate cancer progression of SOX2, providing potential targets for prostate cancer treatment.

Background: The transformation of myelodysplastic syndromes (MDS) into acute myeloid leukemia (AML) is common, while it is extremely rarely for acute lymphoblastic leukemia (ALL) transformation. Herein, we described the clinical and cytogenetic features of a case of MDS with del(20q) transformed into B-lineage ALL (B-ALL) remaining with del(20q).

Case presentation: A 66-year-old Chinese man who presented with pancytopenia, bone marrow hypercellularity and obvious megakaryocytes dysplasia were admitted for treatment. Karyotype analysis of leukemic cells revealed the clonal abnormality of del(20q) and he was diagnosed with MDS carrying del(20q). He was administrated with Danazol, cyclosporin A, and lenalidomide for 3 months, and then discontinued due to poor efficacy, severe swelling and aching of gum. He was subsequently treated with Chinese herbs and uninterrupted platelet infusion. After 41 months, this patient evolved into B-ALL. Cytogenetics demonstrated that in addition to the previous abnormality of del(20q), an emerging clonal abnormality of + 21 was observed. Unfortunately, the patient failed to achieve remission after receiving conventional treatment and other symptomatic supportive treatment.

Conclusion: This study reported a rare case of B-ALL with del(20q) following MDS with del(20q), and conducted a literature review to explore the clinical features and potential mechanisms of disease transformation in patients with MDS progression to ALL. Collectively, this study will help enrich the knowledge of MDS progression to ALL.

Objective: In light of the incompletely defined metastatic patterns inherent to rhabdomyosarcoma (RMS), our objective was to analyze the clinicopathological attributes of various metastatic sites in patients afflicted with RMS. Additionally, we sought to identify population-level risk factors that contribute to metastasis in patients.

Methods: Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2000 to 2017, our study included a cohort of 1,300 patients diagnosed with RMS, each presenting with specific instances of metastasis. Statistical comparisons of categorical variables between groups were conducted using the chi-squared test or Fisher's exact test. Survival curves were constructed employing the Kaplan-Meier method and their comparative analysis was conducted using the log-rank test. Identification of the risk factors associated with site-specific metastasis in patients diagnosed with RMS was undertaken through the application of multivariate logistic regression analysis.

Results: The observed incidence rates of metastasis to the lung, bone, liver, and brain among patients diagnosed with RMS were 13.1, 12.3, 2.5, and 1.2% respectively. The presence of lung, bone, liver, and brain metastases in patients with RMS was associated with a statistically significant reduction in cancer-specific survival. Factors indicative of increased risk for the development of lung metastasis in patients with RMS include male gender (in comparison to female), larger tumor volume, and tumor location in unfavorable sites (as compared to favorable sites). Risk factors for the occurrence of bone metastasis were male (as compared to female), larger tumor volume, and alveolar RMS (as compared to embryonal RMS). The median CSS for patients diagnosed with RMS and presenting with lung, bone, liver, and brain metastases were 15, 19, 5, and 8 months, respectively.

Conclusion: Through an analysis of site-specific metastasis in patients diagnosed with RMS, we identified risk factors associated with lung and bone metastasis. These findings are of considerable significance for clinicians, are of considerable significance during the pre-treatment evaluation phase. The application of these findings has the potential to extend the survival duration of patients with RMS.