Discover. Oncology最新文献

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.

Background: Immune checkpoint blockade (ICB) therapy, including antibodies targeting the programmed cell death protein 1 (PD-1) pathway, has significantly prolonged the overall survival (OS) in patients with advanced cervical cancer (CC). ICB treatment affects both target cells and various components released by immune cells, which can be observed in peripheral blood. However, there has been limited research on the dynamics of peripheral blood immunophenotyping and its association with OS in CC patients receiving ICB therapy.

Methods: Patients with persistent, recurrent, or metastatic CC treated with ICB were enrolled between December 2019 and September 2022. The dynamic changes in peripheral blood immune cells, immunoglobulins, and complement components were analyzed at baseline (within 30 days prior to the first ICB cycle) and after the second cycle of ICB treatment (4-6 weeks after the first ICB treatment). Associations of the baseline levels of peripheral blood immune cells, immunoglobulins, complement components with OS were analyzed using multivariable Cox regression analysis.

Results: In this retrospective cohort study, 119 patients who received at least two cycles of ICB were included. Data on peripheral blood immune cells, immunoglobulins, and complement components were available for 70 of these patients. The percentages of suppressor T (Ts) cells and natural killer (NK) cells in peripheral blood increased significantly post-ICB treatment, whereas the Th/Ts ratio and IgM levels decreased. The percentages of cytotoxic T (Tc) cells, Ts cells, the Th/Ts ratio, and levels of IgM, IgA, C3, and C4 were significantly associated with the OS of patients. Furthermore, multivariable Cox regression analysis found that a high level of IgA was associated with poor OS of the patients (HR = 2.918; 95% CI, 1.081-7.877, P = 0.035).

Conclusion: Our study demonstrated the potential proliferation of peripheral blood anti-tumor T cells in some CC patients undergoing ICB therapy. The observed associations between peripheral blood immunophenotyping and OS suggest that these biomarkers might have potential as prognostic tools.

Lung cancer is one of the deadliest malignancies worldwide, with distant metastasis being a major cause of death. However, the specific mechanisms of lung cancer metastasis remain unclear. NcRNAs, a widely present type of non-coding RNAs in the body, constitute about 98% of the human genome, lacking protein-coding capacity but involved in various cellular processes such as proliferation, apoptosis, invasion, and migration. Studies have shown that ncRNAs play a crucial role in the metastasis of lung cancer, although research in this area is limited. This review summarizes the biological origins and functions of ncRNAs, their specific roles and mechanisms in lung cancer metastasis, and discusses their potential for early screening and therapeutic applications in lung cancer. Furthermore, it outlines the challenges in translating basic advancements of ncRNAs in lung cancer metastasis into clinical practice.

Background: Liver cancer is a common second primary cancer in gastric cancer patients, but whether a gastric cancer diagnosis contributes to the development of second primary liver cancer remains contentious. This study aims to utilize Mendelian randomization (MR) analysis to investigate the potential causal relationship between gastric cancer and second primary liver cancer from a genetic perspective.

Methods: We extracted single nucleotide polymorphism for gastric cancer and liver cancer in the East Asian population from the Genome-Wide Association Studies database as instrumental variables and employed univariate and multivariate MR analysis to evaluate the causal relationship between gastric cancer and liver cancer. The robustness of the findings was ensured through heterogeneity and sensitivity analyses.

Results: Univariate MR analysis revealed that genetic susceptibility to gastric cancer in the East Asian population was significantly associated with an increased risk of liver cancer [Inverse-variance weighted (IVW): OR = 1.252, 95% CI 1.076-1.457, P = 0.004]. Multivariate MR analysis indicated that after adjusting for confounding factors, the significant positive causal relationship between gastric cancer and liver cancer remained robust (all P < 0.05). Furthermore, no causal relationship was observed between liver cancer diagnosis and the development of gastric cancer in the East Asian population (IVW: OR = 1.111, 95% CI 0.936-1.318, P = 0.228).

Conclusion: Genetic prediction results suggest that gastric cancer survivors might face an increased risk of developing second primary liver cancer, implying the potential value of routine liver cancer screening for gastric cancer survivors.

Background: Immunotherapy is an effective treatment for BRAF V600E-mutant colorectal cancer, but currently, only a few benefit from it. Therefore, exploring new immunotherapy strategies is essential.

Methods: We obtained RNA sequencing data and clinical information of colorectal cancer patients from the TCGA and GEO databases. The impact of the BRAF V600E mutation on tumor microenvironment characteristics, gene expression, and signaling pathways was evaluated using bioinformatics approaches. Weighted gene co-expression network analysis (WGCNA) were used to identify core genes associated with T cell dysfunction. Consensus clustering was applied for subtype construction. Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) algorithms were employed to filter potential immunotherapy targets.

Results: We found that BRAF V600E mutation has a complex impact on the immune profile of colorectal cancer. It increases immune cell infiltration and activates immune-related signaling pathways, yet it also severely restricts T cell function. We subsequently identified 39 core genes associated with T cell dysfunction and constructed subtypes of BRAF V600E colorectal cancer based on their expression profiles. Significant heterogeneity was observed between these subtypes in immune signaling pathway activity, immune infiltration patterns, immune phenotype scores, and mechanisms of resistance to immunotherapy. Ultimately, using machine learning algorithms and bioinformatics validation, we identified IDO1 as a potential immunotherapy targets for BRAF V600E-mutant colorectal cancer.

Conclusion: This study constructed novel T cell dysfunction molecular subtypes for BRAF V600E-mutant colorectal cancer and identified IDO1 as a potential immunotherapy target, providing a new strategy for immunotherapy.