Discover. Oncology最新文献

Oral potentially malignant disorders (OPMDs), such as oral lichen planus (OLP) and oral leukoplakia (OLK), are clinical conditions associated with the risk of developing oral squamous cell carcinoma; however, no standardized treatment guidelines exist. Mutations in specific genes, known as oral cancer driver gene mutations (ODGMs), are responsible for carcinogenesis. We aimed to analyze the ODGMs in OPMDs and investigate their clinical correlations. We investigated 41 cases of OPMDs, including OLP and OLK, and performed next-generation sequencing using a custom gene panel targeting whole exons of TP53, HRAS, PIK3CA, NOTCH1, CDKN2A, FBXW7, and BRAF. We detected ODGMs in four OLK cases and one OLP case. All ODGM-positive OLK cases were located in the tongue, a site associated with a higher risk of malignant transformation compared with those in other oral sites. Moreover, ODGMs were significantly associated with alcohol consumption. While there was a tendency for mutations to increase with higher grades, we found no significant correlation between the presence of ODGMs and oral epithelial dysplasia (OED) grade. Notably, in the case of OLP with ODGM, the lesion histopathologically developed OED during the follow-up period, indicating an increased risk of cancer development and that cases with identified ODGMs require early surgical excision. These findings suggest that ODGM analysis may predict the risk of cancer development in OPMDs that are difficult to diagnose using histopathological examination alone.

Cuproptosis, a newly suggested mechanism of controlled cellular demise, which has been extensively associated with aspects of occurrence and development in breast cancer. The aim of this study was to conduct a comprehensive multi-group bioinformatics analysis based on the expression of cuproptosis-related genes (CRGs) to identify novel breast cancer subtypes to guide clinical practice. We collected TCGA-BRCA and GSE42568 datasets to investigate the expression patterns of CRGs in breast cancer. Consensus cluster analysis was performed to identify distinct subtypes. Subsequently, an investigation was carried out to examine the disparities between CRGclusters through functional enrichment analysis. Finally, we examined microsatellite instability, tumor mutation burden, drug sensitivity, infiltration of immune cells and cancer cell stemness across different CRGclusters. We identified two subtypes, where CRGcluster S2 exhibits a poorer prognosis compared to CRGcluster S1. Moreover, CRGcluster S2 demonstrated lower immune infiltration scores, higher cancer cell stemness index, and increased tumor mutation burden relative to CRGcluster S1, with the most frequently mutated gene being ATP7A. Notably, breast cancer chemotherapy drugs such as docetaxel, doxorubicin, and paclitaxel exhibited reduced sensitivity towards CRGcluster S2 when compared to CRGcluster S1. We have identified two CRGclusters in breast cancer that could serve as potential therapeutic targets and warrant further investigation in clinical trial studies for breast cancer.

Background: Diseases are often caused by multiple factors, regulatory T cells specific genes (RTSGs) have been shown to be associated with cancer, however, their role in prostate cancer (PRAD) has not been fully explored.

Methods: RTSGs associated with PRAD prognosis were identified using Cox regression analysis and LASSO analysis. Furthermore, a prognostic model was constructed in PRAD based on the 4 RTSGs, and its biological function were analyzed. We evaluated the differences in tumor immune microenvironment based on prognostic signature. Finally, cell experiments confirmed the function of synaptonemal complex protein-2 (SYCP2) in PRAD cells.

Results: The prognostic value of RTSGs in PRAD patients has been comprehensively analyzed for the first time and identified four RTSGs with prognostic values. A prognosis risk model was constructed based on four RTSGs and its prognostic value was validated on an independent external PRAD dataset. In PRAD patients, this prognostic feature is an independent risk factor and was significantly correlated with clinical feature information of PRAD patients. This feature is also related to the immune microenvironment of PRAD. Cell experiments have confirmed that SYCP2 regulates the apoptosis and cycle progression of PRAD cells significantly. Therefore, SYCP2 may become an important regulatory factor in the progression of PRAD by participating in intracellular functional regulation.

Conclusions: This research provides a fundamental theoretical basis for improving the diagnosis and treatment of PRAD in clinical practice.

Y RNAs are a class of highly conserved small non-coding RNAs. Emerging evidences reported that Y RNAs and their Y RNA-derived small RNAs (YsRNAs) represent bioactive molecules and not simply structural RNAs involved in scaffolding and assembling. They can interact and regulate both localization and functions of several RNA-binding proteins implicated in a wide range of cellular processes such as DNA replication, RNA quality control and cellular stress responses. More evidences suggest functional involvement of Y RNAs in several type of disease such as cancer, immune related pathologies, neurological disorders and cardiovascular diseases. Nevertheless, there are many questions that still need to be answered for their functional and mechanistic understanding in a physiological and in a pathological context. In this review we will describe the current state of knowledge about YRNAs, their structure, biogenesis, functions and interaction with known proteins, as well their role in disease. The picture arising indicates their potential function as biomarkers for disease diagnosis, as well as therapeutical targets for building up tailored approaches in personalized medicine.

Background: Autologous hematopoietic stem cell transplantation (AHSCT) is a valuable treatment option for several hematological malignancies, particularly in relapsed or refractory cases. Autologous hematopoietic stem cell transplantation (AHSCT) is effective in improving survival rates in selected patients, particularly those with aggressive lymphomas and multiple myeloma. Studies suggest AHSCT may outperform alternative therapies, but ongoing research is essential to refine patient selection. Many patients enjoy prolonged remission and improved quality of life, indicating the need for long-term follow-up to assess late effects and overall survival. This work aimed to establish meta-analysis to methodically evaluate the safety and effectiveness of autologous stem cell therapy (AHSCT) in the management of malignant lymphoma following high-dose chemotherapy and to produce reliable findings that may serve as a foundation for clinical application and reference.

Methods: A systematic literature search was performed from February 2017 to August 2024, and malignant lymphoma was identified as the study subjects' diagnosis. The experimental group was identified as AHSCT afterwards high-dose chemotherapy, while the control group underwent standard chemotherapy (with no restrictions on the chemotherapy regimen). The outcome indicators were progression-free survival (PFS), complete remission rate (complete response (CR) + partial response (PR)), and overall survival (OS).

Results: Fifteen literature pieces in all, consisting of 1229 subjects in the control group and 896 subjects in the experimental group, were included. Conventional chemotherapy (chemotherapy regimen not limited) was the intervention strategy used in the control group. The odds ratio (OR) was 2.23, with a 95% confidence interval (CI) of [1.54, 3.22], Z = 4.25; P < 0.0001, indicating that the groups differed in overall survival and progression-free survival rates. Similarly, the progression-free survival rate was 2.70, with a 95% CI of 1.86-3.92, Z = 4.25; P < 0.0001, and overall survival was 2.23.

Conclusions: Patients with malignant lymphoma who receive chemotherapy can substantially extend their overall survival and progression-free survival rates with AHSCT treatment.

Background: N-acetyltransferase 10 (NAT10) is involved in several cellular processes. NAT10 expression is essential for the promotion of mRNA translation and stability.  In some situations, deregulation of NAT10 has been attributed to the development of multiple types of cancer. NAT10 is significantly upregulated in various gastrointestinal tumors, including esophageal, colorectal, pancreatic, and liver cancers, and is correlated with poor prognosis. Additionally, NAT10 expression contributes to chemotherapy resistance in both esophageal and colorectal cancers. Nevertheless, the role of NAT10 in gastric cancer (GC), a type of gastrointestinal tumor, is not fully understood.

Methods: Throughout this investigation, our team evaluated NAT10 expression levels in GC patient samples and databases available to the general public. Based on the knockdown and overexpression of NAT10, in vitro experiments were conducted to examine the effects of NAT10 on GC progression and resistance to chemotherapy.

Results: Our study demonstrated that GC tissues exhibit increased levels of NAT10. Downregulation of NAT10 decreased GC cell proliferation, migration, and invasiveness. Conversely, upregulation of NAT10 resulted in the opposite effect. Furthermore, NAT10 fosters the progression of GC cells by activating the Wnt/β-catenin signaling pathway. NAT10 also promotes resistance to cisplatin chemotherapy.

Conclusions: Our findings indicated that expression of NAT10 promoted GC progression through activation of the Wnt/β-catenin signaling pathway. We investigated the effect of NAT10 on the viability of GC cells treated with different doses of cisplatin. The results showed that NAT10 expression could impact the effectiveness of chemotherapy resistance in GC. This implies that using NAT10 as a target may be a potential therapeutic strategy for treating GC.

Background: Aberrant miRNA expression has been associated with cervical cancer (CC) progression. The present study aimed to identify the miRNA clusters (MCs) altered in CC, identify their clinical utility, and understand their biological functions via computational analysis.

Methods: We used small RNA sequencing and qRT‒PCR to identify and validate abnormally expressed MCs in cervical squamous cell carcinoma (CSCC) samples. We compared our data with publicly available CC datasets to identify the differentially expressed MCs in CC. The potential targets, pathways, biological functions, and clinical utility of abnormally expressed MCs were predicted via several computational tools.

Results: Small RNA sequencing revealed that 229 miRNAs belonging to 48 MCs were significantly differentially expressed in CSCC (p-value ≤ 0.05). Validation by qRT‒PCR confirmed the downregulation of members of the miR-379/656, namely, hsa-miR-376c-3p (2.8-fold; p-value 0.03), hsa-miR-494-3p (3.4-fold; p-value 0.02), hsa-miR-495-3p (eightfold; p-value 0.01), and hsa-miR-409-3p (fivefold; p-value 0.03), in CSCC samples compared with normal samples. The prognostic model generated via miRNA expression and random forest analysis showed robust sensitivity and specificity (0.88 to 0.92) in predicting overall survival. In addition, we report 22 prognostically important miRNAs in CC. Pathway analysis revealed the enrichment of several cancer-related pathways, notably p53, the cell cycle, viral infection and MAPK signalling. CDC25A, CCNE1, E2F1, CCNE2, RBL1, E2F3, CDK2, RBL2, E2F2 and CCND2 were identified as the top ten gene targets of MC. Drug‒gene interaction analysis revealed enrichment of 548 approved drugs and 62 unique genes.

Conclusion: Our study identified MCs, their target genes, their prognostic utility, and their potential functions in CC and recommended their usefulness in CC management.

As a primary brain cancer, glioma presents significant challenges in treatment and prognosis. Identifying reliable biomarkers is crucial for improving patient outcomes. This study focuses on the ABCC3 gene, exploring its function as a standalone predictive indictor and its correlation with immune infiltration and resistance to chemotherapy in glioma. A multi-faceted approach was adopted for this analysis. We scrutinized the RNA expression patterns of the ABCC3 gene across a spectrum of cancer types, with a concentrated focus on glioma. Our methodological arsenal included bioinformatics analysis, immunohistochemistry (ICH), western blot (WB), and cell counting Kit-8 (CCK8) assays. These techniques were instrumental in gauging the prognostic impact of ABCC3 and elucidating its associations with immune cell infiltration and chemotherapy resistance. The investigation revealed a significant elevated levels of ABCC3 in high grade glioma (HGG) tissues compared to lower grade glioma (LGG) tissues. Notably, upregulation of ABCC3 were associated with a shorter overall survival in patients with glioma. Furthermore, ABCC3 emerged as an independent factor in prognostication, with predictive capability for 1-, 3-, and 5-year survival rates. As far as immune response is concerned, ABCC3's expression correlates positively with the expression of several immune cells and checkpoint genes. The study also uncovered the role of ABCC3 in drug resistance, particularly regarding temozolomide (TMZ), a primary therapeutic agent in glioma treatment. The study reveals ABCC3 as a significant biomarker in glioma, associated with lower survival, enhanced immune infiltration, and increased resistance to chemotherapy. These findings emphasize its promise as a novel target for glioma therapies.

Introduction: The prognosis of ground glass opacity featured lung adenocarcinomas (GGO-LUAD) is significantly better than that of solid nodule featured lung adenocarcinomas (SN-LUAD), but the specific reasons behind their indolent tumor behavior are still unclear. The purpose of this study is to investigate their differences in intratumoral microvessels, related angiogenic factors and important stromal cells.

Methods: Thirty patients (15 paired patients only with GGO or SN) diagnosed with pathological stage 0-I lung adenocarcinoma who underwent surgical treatment were included into this study. Immunohistochemistry was performed to stain the blood vessel markers (CD31, CD34 and CD105), LYVE-1, the cancer-associated fibroblasts (CAFs) markers (α-SMA and S100A4), TGF-β and HIF-1α from 30 patients tissue sections. At the same time, Ki67 Labeling Index (LI) extracted from pathological report of all patients was also analyzed.

Results: GGO-LUAD is more abundant than SN-LUAD in lymphatic vessel density (LVD), but similar in total microvessel density (CD31 + MVD). However, GGO-LUAD is significantly lower than SN-LUAD in CD34 + MVD and CD105 + MVD. In terms of TGF-β, HIF-1α expression and Ki67 LI level, GGO-LUAD was also significantly weaker than SN-LUAD. Moreover, the distribution of CAFs in GGO-LUAD is less than that in SN-LUAD. Regardless of the pathological type (adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) or invasive lung adenocarcinoma (IAC)), there is no difference in any of the above indicators in GGO-LUAD.

Conclusions: Our finding displays that GGO-LUAD was significantly lower than SN-LUAD in CD34 + MVD and CD105 + MVD reflecting tumor angiogenesis, and the distribution of CAFs and factors related to tumor angiogenesis were also significantly lower in GGO-LUAD, which may indicate that the weak ability of angiogenesis might be the reason for the good prognosis of GGO-LUAD.

Background: Prostate cancer (PCa) is the second most common malignant neoplasm in males and is the fifth leading cause of cancer-related mortality. Due to the use of prostate-specific antigen (PSA) screening and improved biopsy techniques, persons identified with early-stage prostate cancer often have a positive prognosis after comprehensive treatment. Nonetheless, prostate cancer is a latent illness that may present as an asymptomatic tumor in individuals aged 20-30. The overall survival (OS) of men with advanced PCa is significantly diminished. Consequently, there is an immediate want for innovative, accurate biomarkers to detect early prostate cancer.

Methods: This research analyzed the interaction network of differentially expressed genes (DEGs) related to metabolite interconversion enzymes in PCa by gene expression microarray data, single-cell RNA sequencing, oncogenes, and tumor suppressor genes (TSGs) utilizing bioinformatics techniques. This kind of analysis has not been documented in prior studies.

Results: We then used a dataset acquired by the Cancer Genome Atlas (TCGA) to confirm our findings. Genes including CYP3A5, PDE8B, AOX1, BNIPL, FADS2, RRM2, ALDH3B2, and GSTM2 may be significant in the diagnosis and treatment of PCa.

Conclusion: Our objective was to provide new perspectives on the molecular properties and pathways of DEGs in PCa and to uncover potential biomarkers that play a crucial role in the genesis and progression of PCa.