Discover. Oncology最新文献

Monotherapy with anti-programmed cell death protein 1 (PD-1) monoclonal antibody has been approved for the treatment of advanced non-small cell lung cancer with positive programmed cell death-ligand 1 (PD-L1) expression and oncogene wild type, which revealed survival benefit compared with chemotherapy. Nevertheless, certain patients develop rapid progression on anti-PD-1 inhibitor monotherapy. This novel pattern is called hyperprogressive disease (HPD), and the underlying mechanism and molecular characteristics still leaves not clear. Here, we reported two heavily pretreated advanced lung adenocarcinoma cases with HER2 exon 20 insertion who presented HPD after two cycles of anti-PD-1 inhibitor sintilimab monotherapy, and they both carried co-alterations in the PI3K/AKT/mTOR and cell cycle signaling pathway. We speculated that HER2 exon 20 insertion might be viewed as a potential biomarker to avoid single-agent immunotherapy in certain patients with driver mutations, or timely guide proper treatment strategies.

Background: Currently, serum PSA is the most commonly used screening tool in clinical practice. However, PSA levels in the range of 4-10 ng/ml are considered the 'grey zone' of prostate cancer screening. Patients within this range need to be further evaluated using additional parameters such as PSA ratio, PSA density, and other indices to determine the necessity of prostate biopsy (PBx). Despite this, patients in the 'grey zone' still have a low rate of positive biopsy results. Neutrophils have been found to be associated with tumor development and inflammation. Based on this, we combined PSA and absolute neutrophil counts to calculate the total PSA to absolute neutrophil ratio (PNR), which is higher in patients with prostate cancer and lower in those with benign conditions. PNR is elevated in prostate cancer patients compared to those with prostate enlargement. Therefore, the aim of this study is to explore the diagnostic efficacy of PNR for prostate cancer across different PSA intervals and to provide new insights into the diagnosis, treatment, and screening strategies for prostate cancer.

Objective: In this study, we explored the predictive value of prostate-specific antigen-to-neutrophil ratio (PNR) for the diagnosis of prostate cancer, with a view to further improving the diagnostic accuracy of prostate cancer.

Methods: Patients were grouped in three different divisions of PSA 4-10 ng/ml, 10-20 ng/ml, > 20 ng/ml, We grouped the patients and compared the test data such as age, PSA, PSA-density (PSAD), and prostate-specific antigen-to-neutrophil ratio (PNR) between the two groups of patients who had puncture results of prostate cancer and non-prostate cancer at the same time using Log regression test to verify the diagnostic value of PNR.

Results: When PSA levels are in the range of 4-10 ng/ml, an elevated PNR is an independent risk factor for prostate cancer. In this range, the diagnostic value of f/t PSA and PSAD for prostate cancer is limited. However, the use of PNR can significantly enhance the diagnostic efficacy for prostate cancer and thereby effectively reduce the incidence of unnecessary prostate biopsies.

Background: Gastric cancer (GC) has a poor prognosis, considerable cellular heterogeneity, and ranks fifth among malignant tumours. Understanding the tumour microenvironment (TME) and intra-tumor heterogeneity (ITH) may lead to the development of novel GC treatments.

Methods: The single-cell RNA sequencing (scRNA-seq) dataset was obtained from the Gene Expression Omnibus (GEO) database, where diverse immune cells were isolated and re-annotated based on cell markers established in the original study to ascertain their individual characteristics. We conducted a weighted gene co-expression network analysis (WGCNA) to identify genes with a significant correlation to GC. Utilising bulk RNA sequencing data, we employed machine learning integration methods to train specific biomarkers for the development of novel diagnostic combinations. A two-sample Mendelian randomisation study was performed to investigate the causal effect of biomarkers on gastric cancer (GC). Ultimately, we utilised the DSigDB database to acquire associations between signature genes and pharmaceuticals.

Results: The 18 genes that made up the signature were as follows: ZFAND2A, PBX4, RAMP2, NNMT, RNASE1, CD93, CDH5, NFKBIE, VWF, DAB2, FAAH2, VAT1, MRAS, TSPAN4, EPAS1, AFAP1L1, DNM3. Patients were categorised into high-risk and low-risk groups according to their risk scores. Individuals in the high-risk cohort exhibited a dismal outlook. The Mendelian randomisation study demonstrated that individuals with a genetic predisposition for elevated NFKBIE levels exhibited a heightened likelihood of acquiring GC. Molecular docking indicates that gemcitabine and chloropyramine may serve as effective therapeutics against NFKBIE.

Conclusions: We developed and validated a signature utilising scRNA-seq and bulk sequencing data from gastric cancer patients. NFKBIE may function as a novel biomarker and therapeutic target for GC.

Cancer therapy continues to face critical challenges, including drug resistance, recurrence, and severe side effects, which often compromise patient outcomes and quality of life. Exploring novel, cost-effective approaches, this review highlights the potential of Piper nigrum (black pepper) extract (PNE) as a complementary anticancer agent. Piper nigrum, a widely available spice with a rich history in traditional medicine, contains bioactive compounds such as piperine, which have demonstrated significant anticancer activities including cell cycle arrest, apoptosis induction, and inhibition of tumor growth and metastasis. The review evaluates the recent findings from in vitro, in vivo, and clinical studies, emphasizing PNE's capacity to enhance the efficacy of conventional chemotherapeutic agents while mitigating their side effects. Key mechanisms underlying these effects include oxidative stress modulation, suppression of pro-metastatic factors, and synergistic interactions with established drugs like doxorubicin and paclitaxel. These interactions suggest that PNE could play a pivotal role in overcoming chemoresistance and improving therapeutic outcomes. Furthermore, this review highlights the potential benefits of PNE in resource-limited settings, where the cost of cancer treatments often restricts access. However, challenges such as compositional variability, limited bioavailability, and the need for standardization and clinical validation need to be addressed to advance the integration of PNE into basic oncology. By providing a comprehensive analysis of the anticancer mechanisms of PNE and its potential as a cost-effective adjuvant therapy, this review provides new insight into the exploitation of Piper nigrum to improve cancer treatment efficacy while reducing side effects. Future research directions are discussed to address current limitations and facilitate clinical translation.

A common digestive system cancer with a dismal prognosis and a high death rate globally is breast cancer (BRCA). BRCA recurrence, metastasis, and medication resistance are all significantly impacted by cancer stem cells (CSCs). However, the relationship between CSCs and the tumor microenvironment in BRCA individuals remains unknown, and this information is critically needed. Our research utilized bioinformatics techniques and TCGA data to explore the complex relationship between CSCs and BRCA development. We identified 26 stem cell gene sets from the Stem Checker database and classified BRCA samples into stemness subtypes using consensus clustering. Prognosis, tumor microenvironment (TME) elements, and treatment responses varied across subtypes. Using LASSO, Cox regression, and differential expression analysis, we developed a stemness-risk model. BRCA patients were divided into two groups (Cluster A and Cluster B). Cluster B exhibited an improved prognosis, higher PIK3CA mutation frequency, and increased levels of CD8 T cells and regulatory Tregs. A 5-gene stemness model was constructed, showing that higher stemness scores correlated with poorer prognosis. The model was validated using the METABRIC cohort data from cBioPortal. Our findings identify two stemness-related subgroups with distinct prognoses and TME patterns. Further experimental validation is necessary before this model can be considered for clinical application.

Gastric cancer (GC), one of the most common and heterogeneous malignancies, is the second leading cause of cancer death worldwide and is closely related to dietary habits. Fatty acid is one of the main nutrients of human beings, which is closely related to diabetes, hypertension and other diseases. However, the correlation between fatty acid metabolism and the development and progression of GC remains largely unknown. Here, we profiled the genetic alterations of fatty acid anabolism-related genes (FARGs) in gastric cancer samples from the TCGA cohort and GEO database to evaluate the possible relationships and their internal regulatory mechanism. Through consistent clustering and functional enrichment analysis, three distinct fatty acid anabolism clusters and three gene subtypes were identified to participate in different biological pathways, and correlated with the characteristics of immune cell infiltration and clinical prognosis. Importantly, a distinctive FA-score was constructed through the principal component analysis to quantify the characteristics of fatty acid anabolism in each GC patient. Further analysis showed patients grouped in the high FA-score group were characterized with greater tumor mutational burden (TMB) and higher microsatellite stability (MSI-H), which may be more aeschynomenous to immunotherapy and had a favorable prognosis. Altogether, our bioinformatics analysis based on FARGs uncovered the potential roles of fatty acid metabolism in GC, and may provide newly prognostic information and novel approaches for promoting individualized immunotherapy in patients with GC.

Objective: Circulating protein level ratios (CPLRs) may play a crucial role in tumor progression and drug resistance by mediating interactions within the tumor microenvironment. This study aims to investigate the causal associations between CPLRs and papillary thyroid cancer (PTC), focusing on their potential implications in drug resistance mechanisms.

Methods: Genetic data for 2821 CPLRs were obtained from the GWAS and FinnGen databases. Mendelian randomization (MR) analysis, using inverse variance weighting (IVW) as the primary method, was conducted to explore causality. Sensitivity analyses, including heterogeneity and pleiotropy tests, were performed to ensure the robustness of the results.

Results: Twelve CPLRs were identified as causally associated with PTC. Seven CPLRs, such as REG1A/TFF3 and LAT/SPARC, were associated with reduced PTC risk, potentially reflecting protective mechanisms. In contrast, five CPLRs, including MAD1L1/PSIP1 and CIAPIN1/TYMP, were linked to increased risk, suggesting their role in promoting drug resistance. Reverse MR analysis revealed no significant causal associations, reinforcing the directionality of these findings.

Conclusion: These findings highlight the relevance of CPLRs in the pathogenesis and drug resistance of PTC, providing insights into potential biomarkers and therapeutic targets. Future research could focus on translating these findings into strategies for personalized medicine and targeted treatment.

The prominence of circular RNAs (circRNAs) has surged in cancer research due to their distinctive properties and impact on cancer development. This review delves into the role of circRNAs in four key cancer types: colorectal cancer (CRC), gastric cancer (GC), liver cancer (HCC), and lung cancer (LUAD). The focus lies on their potential as cancer biomarkers and drug targets. Our study analyses the reported circRNAs in the mentioned malignancies, examining their nature, functions, targets, origins, and contributions as tumor enhancers or suppressors. The approach involved assessing full-text reports on PMC, utilizing keywords such as "CircRNA" and "Cancer types," coupled with bioinformatics, experimental assays, or clinical investigations. Exclusions encompassed non-English publications, conference abstracts, letters, and expert opinions. The findings unveil 577 identified circRNAs across these cancer types: 124 in CRC, 177 in GC, 93 in HCC, and 183 in LUAD. Mechanistic insights into how circRNAs modulate gene expression in cancer are explored, particularly their interactions with microRNAs and RNA-binding proteins. Dysregulation of circRNAs across various cancers and their potential as diagnostic and prognostic indicators are synthesized. The exploration extends to the potential of targeting circRNAs as a novel cancer therapy strategy, either through inhibiting oncogenic circRNAs or reinstating tumor-suppressive ones. This article discusses the challenges and prospects in harnessing circRNAs for cancer diagnostics and therapies. These comprehensive analyses hold promise for advancing cancer research and fostering the development of innovative therapies and diagnostics.

Background: The aims of this cohort study were to identify (1) the incidence and risk factors for axillary web syndrome (AWS) with shoulder movement limitation within 4 weeks after axillary lymph node dissection (ALND) for Asian women with breast cancer (BC), and (2) whether early intervention with physical therapy (PT) could improve AWS, and how many PT sessions would be needed.

Methods: A cohort study of patients with BC receiving ALND was performed at Changhua Christian Hospital, Taiwan, between January 2019 and December 2020. Those patients who were diagnosed with AWS with shoulder movement limitation were referred to receive PT twice weekly at the Department of Physical Medicine and Rehabilitation.

Results: A total 173 BC patients receiving ALND were enrolled. The incidence of AWS with shoulder movement limitation was 18%, and the time to diagnosis was 26.3 days. In a subsequent multivariate analysis, younger age (OR = 0.95; 95% CI = 0.91-0.99; p = 0.019), higher number of removed lymph nodes (OR = 1.09; 95% CI = 1.03-1.16; p = 0.007) and receiving neoadjuvant chemotherapy (NAC) (OR = 2.96; 95% CI = 1.25-6.98; p = 0.013) were associated with an increased risk of developing AWS with shoulder movement limitation. The corresponding area under the curve was 0.762. Initial shoulder flexion and abduction were 132.1° and 123.4°, respectively. After 14.8 PT sessions, shoulder flexion and abduction improved to 172.3° and 171.8°, respectively. Improvement in shoulder range of motion was 40.2° and 48.4° in flexion and abduction, respectively, which was significant (p < 0.001).

Conclusions: In conclusion, we demonstrated a prediction model for AWS with shoulder movement limitation using 3 risk factors: younger age, a higher number of removed lymph nodes, and receiving NAC. Approximately 18% of BC survivors will have AWS with shoulder function limitation during the first month after ALND. An early intervention protocol with a PT program could effectively restore shoulder function.