Tonsillar squamous cell carcinoma (TSCC) is characterized by a high tendency to metastasize to lymph nodes, significantly impacting the treatment modality and recurrence rates in head and neck cancer patients. Therefore,...Tonsillar squamous cell carcinoma (TSCC) is characterized by a high tendency to metastasize to lymph nodes, significantly impacting the treatment modality and recurrence rates in head and neck cancer patients. Therefore, the development of accurate predictive models, such as nomograms, is imperative for the early identification of risk factors associated with lymph node involvement. Various lymph node classification systems, including the number of positive lymph nodes (NPLNs), the ratio of positive lymph nodes (pLNRs), and the logarithm of the odds of positive lymph nodes (LODDS), have been proposed to provide prognostic information. However, the optimal system for classifying lymph nodes remains uncertain, necessitating further investigation to determine which system offers the most accurate prediction of patient outcomes. Thus, our objective was to identify the most effective prognostic nomogram for predicting outcomes in TSCC patients. In this study, we retrospectively analyzed data from 1,775 TSCC patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database, following predefined criteria for inclusion. We evaluated the performance of prognostic models using Harrell's concordance index (C-index) and Akaike information criterion (AIC). Subsequently, variables were utilized to construct nomograms for predicting cancer-specific survival and overall survival. Nomograms' predictive capabilities were assessed using Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI). The nomogram comprising pLNR, LODDS, and NPLN showed superior efficacy in predicting the survival outcome of patients with laryngectomy for TSCC. The nomograms developed in this study have the potential to serve as valuable tools for forecasting patient survival following surgical interventions for TSCC.
Due to the poor prognosis and lack of effective therapy options, treating metastatic osteosarcoma (OS), particularly lung metastasis, presents significant therapeutic challenges. It has been shown that both non-coding RN...Due to the poor prognosis and lack of effective therapy options, treating metastatic osteosarcoma (OS), particularly lung metastasis, presents significant therapeutic challenges. It has been shown that both non-coding RNAs (ncRNAs) and protein-coding mRNAs serve as essential for controlling the progression of tumors. Uncertainty persists regarding the whole expression profile and the network of regulation involving competing endogenous RNAs (ceRNAs) between mRNAs and ncRNAs in the OS lung metastasis. To fully understand variations in the expression of lncRNAs, circRNAs, miRNAs, and mRNAs, we introduced whole transcriptome sequencing (RNA-seq) in the three matched primary and lung-metastasis OS tissues used in the current study. Analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) was carried out for mRNAs exhibiting notably distinct expression patterns. After that, the official RNA hybrid and TargetScan databases were utilized to anticipate and establish the ceRNA networks, which are made up of lncRNAs, circRNAs, miRNAs, and mRNAs. Furthermore, two created ceRNA regulatory pathways, lncRNA PCAT1/miR-370-3p/LRAT, and circ_0012586/miR-200b-5p/MFAP5, were chosen at random and verified using a variety of cell and molecular biology experiments. Ultimately, our research may reveal novel avenues for the prevention or treatment of OS lung metastasis as well as fresh evidence for the underlying mechanism.
To evaluate the impact of Huisheng Oral Solution (HSOS) in conjunction with immune checkpoint inhibitors (ICIs) and chemotherapy on patients with stage III-IV non-small cell lung cancer (NSCLC). This retrospective study...To evaluate the impact of Huisheng Oral Solution (HSOS) in conjunction with immune checkpoint inhibitors (ICIs) and chemotherapy on patients with stage III-IV non-small cell lung cancer (NSCLC). This retrospective study included patients with stage III-IV NSCLC who were treated at Sichuan Provincial People's Hospital from May 2018 to June 2021. Patients were categorized into two groups: the ICIs & Chemo Group and the ICIs & Chemo & HSOS Group, based on the therapies administered. The disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) were assessed. A total of 185 patients were included, with 109 patients in ICIs & Chemo & HSOS Group. The ICIs & Chemo & HSOS Group exhibited significantly enhanced DCR (90.83% vs. 71.05%, p=0.001) compared to the ICIs & Chemo Group. The ORR was not statistically significant between the two groups (31.19% vs. 27.63%, p=0.628). Patients in the ICIs & Chemo & HSOS Group had significantly longer PFS (HR=0.47, 95% CI: 0.29-0.75, p<0.001) and OS (HR=0.58, 95% CI: 0.33-1.00, p=0.037) than the ICIs & Chemo Group. In terms of irAEs, nephrotoxicity (5.77% vs. 15.25%, p=0.044), checkpoint inhibitor-related pneumonitis (CIP) (2.75% vs. 11.84%, p=0.014), and cardiotoxicity (0% vs. 13.04%, p=0.026) were significantly lower in the ICIs & Chemo & HSOS Group. The addition of HSOS to ICIs and chemotherapy may enhance DCR, PFS, and OS, while concurrently reducing irAEs in patients with stage III-IV NSCLC. These findings suggest that HSOS may serve as a promising adjunct to ICI-based therapies. Further prospective studies are warranted to validate these results.
Immunogenic cell death (ICD) represents a specific form of regulatory cell death that initiates an adaptive immune response. We aimed to investigate the significance of immunogenic cell death-related genes (ICDGs) in AML...Immunogenic cell death (ICD) represents a specific form of regulatory cell death that initiates an adaptive immune response. We aimed to investigate the significance of immunogenic cell death-related genes (ICDGs) in AML, utilizing a combination of bioinformatics analysis, consensus clustering, functional enrichment analysis, and experimental validation in cell lines and animal models. Here, we identified 34 ICDGs, and single-cell analysis indicated that CD8 T cells and NK cells exhibited gene expression patterns closely associated with ICD. Consensus clustering revealed two distinct subtypes of AML (ICD-high and ICD-low), with the former correlating with more favorable clinical outcomes and heightened infiltration of immune cells. A predictive model was established through LASSO regression, yielding a risk signature comprising six key ICDGs (FGFBP2, GZMB, ALPK2, NELL2, OPTN, FCGR2B), which successfully categorizes patients into high-risk and low-risk cohorts based on overall survival outcomes. Notably, HSPA6 emerged as a critical ICDG, with its knockdown in OCI-AML3 cells significantly inhibiting proliferation and inducing apoptosis, suggesting its potential as a therapeutic target. In summary, our research emphasizes the importance of ICD-related genes in predicting the prognosis of AML and initiates the development of a prognostic risk signature that may pave the way for personalized treatment strategies while highlighting the need for further validation and exploration of HSPA6 in AML.
Chemerin is a protein, encoded by the gene, which has important roles in immune regulation, inflammation and metabolic regulation. Chemerin can affect the proliferation, migration and invasion ability of tumor cells and...Chemerin is a protein, encoded by the gene, which has important roles in immune regulation, inflammation and metabolic regulation. Chemerin can affect the proliferation, migration and invasion ability of tumor cells and is important in the occurrence, development, metastasis, differentiation and development of tumors. CMKLR1, GPR1, and CCRL2, the primary cellular receptors for chemerin, can be found in both normal and tumor tissues. Chemerin binds to its receptors to influence tumor growth and metastasis by regulating the inflammatory response and tumor microenvironment. In this paper, the mechanism of chemerin and its receptors in the tumor microenvironment was summarized, providing theoretical basis for further study of the mechanism of chemerin in tumors and for molecular targeted therapy based on chemerin.
Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI); it has achieved favorable progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients with EGF...Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI); it has achieved favorable progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients with EGFR mutation, however, the resistance occurs in most patients, and the underlying mechanism remain to be elucidated. Cancer-associated fibroblasts (CAFs) are major stromal cells in tumor microenvironment. Despite accumulating evidence suggests that CAFs contribute to drug resistance, the role of CAFs in osimertinib resistance in NSCLC is not fully understood. Here, we reported that CAFs promoted the resistance of NSCLC cells to osimertinib through enhancing stemness of NSCLC cells and reducing apoptosis induced by osimertinib. CAFs possessed a high level of Neuregulin-1 (NRG1), and CAFs-secreted NRG1 mediated the promoting effect of CAFs on osimertinib resistance, demonstrated by applying recombinant human NRG1 (rhNRG1) and NRG1 knockdown. We also found that osimertinib stimulated NRG1 secretion by CAFs, which may further enhance osimertinib resistance. Further study revealed that CAFs promoted the resistance of NSCLC cells to osimertinib via NRG1-mediated HER3/AKT/NF-κB pathway. Moreover, the mouse xenograft study demonstrated that CAFs enhanced osimertinib-treated tumor growth . Our finding highlights the potential value of CAFs-derived NRG1 as a novel therapeutic target for osimertinib resistance in lung cancer.
: Despite the implementation of laparoscopic and robotic-assisted liver resection (LLR vs. RLR) in many centers, there remains controversy surrounding the differences in perioperative outcomes between the two approaches....: Despite the implementation of laparoscopic and robotic-assisted liver resection (LLR vs. RLR) in many centers, there remains controversy surrounding the differences in perioperative outcomes between the two approaches. This study aims to clarify the discrepancies in perioperative outcomes between LLR and RLR through a prospective study. Patients with HCC received LLR or RLR were included. The postoperative complications were categorized and evaluated employing the standardized Clavien-Dindo classification and the Comprehensive Complication Index (CCI) score. Specifically, the median CCI of 20.9 was set as the cut-off value for the occurrence of severe complications. A 1:2 propensity score matched (PSM) analysis was performed to control confounding bias. A total of 273 patients were included, of whom 213 (78%) patients received LLR and 60 (22%) patients received RLR. After PSM, RLR was associated with a longer operative time but shorter hospital stays (all P < 0.05). Postoperative outcomes in terms of overall complications, major and minor complications, and mortality were similar between RLR and LLR groups (all P > 0.05). Of note, RLR is significantly associated with a lower CCI score, especially server complications (OR 0.826, 95%CI 0.386-0.883, P = 0.023). In terms of complication rates, RLR does not reduce the incidence of overall complications when compared to LLR, but it can reduce the severity of complications that occur. RLR, is a feasible and safe approach for patients with HCC.
Colorectal cancer (CRC) is the third most common cancer worldwide. In Saudi Arabia, the 2020 cancer incidence report found that CRC was the most common cancer among men and had the highest mortality rate. Given the corre...Colorectal cancer (CRC) is the third most common cancer worldwide. In Saudi Arabia, the 2020 cancer incidence report found that CRC was the most common cancer among men and had the highest mortality rate. Given the correlation between cancer symptom awareness and early detection and recognizing the significance of patient history in CRC diagnosis, this study aims to identify the presenting symptoms of CRC, assess survival by stage across the population, and better understand disease demographics in Saudi Arabia. We conducted a retrospective cohort analysis of 655 patients with CRC diagnosed between 2016 and 2020, inclusive. The cancer registry database at King Khalid University Hospital was used to retrospectively collect data from electronic records. Various relevant data were extracted and analyzed. The results showed that the most common presenting symptom was abdominal pain (329, 50.2%), followed by weight loss (262, 40%), hematochezia (rectal bleeding or blood in stool) (242, 36.9%), and anemia (238, 36.3%). The overall three-year survival rate was 77.6%. For stages I, II, III, and IV it was 100%, 91.9%, 86.4%, and 61.8%, respectively. with a significant difference (p = 0.0001). Rectal bleeding and other "alarming symptoms" were observed in fewer than 40% of the studied population. In the cohort, only one patient was diagnosed via a screening colonoscopy. Study also confirmed that survival improved with earlier stages at diagnosis. Encouraging preventative measures, raising awareness of CRC, and improving access to screening, could all contribute to earlier identification, reduced staging, and a better prognosis.
: Skin cutaneous melanoma (SKCM) is a malignant tumor characterized by aggressive invasion and a high tendency for metastasis. This study explores the potential of MCM4 as a biomarker for SKCM and its impact on the tumor...: Skin cutaneous melanoma (SKCM) is a malignant tumor characterized by aggressive invasion and a high tendency for metastasis. This study explores the potential of MCM4 as a biomarker for SKCM and its impact on the tumor microenvironment (TME). : A comprehensive analysis of MCM4 was conducted using public databases to characterize the expression, genomic alterations, and clinical significance of MCM4 in pan-cancer, including SKCM. Bioinformatics tools were employed to identify upstream regulators of MCM4. The functional mechanisms of MCM4 in SKCM were explored through correlation, differential, and enrichment analyses. Immune infiltration and drug sensitivity were assessed to understand the role of MCM4 in the TME and its potential therapeutic implications. Functional experiments were performed in A375 and SK-MEL-28 cells. : MCM4 were significantly upregulated in tumors. Survival curves indicated that patients with high MCM4 expression had poor survival advantage. SRF was identified as a potential transcription factor regulating MCM4. Functional enrichment revealed a positive correlation between MCM4 and cell cycle-related pathways, and a negative correlation with immune effector process-related pathways. High MCM4 expression was associated with "cold" tumor characteristics. Immunotherapy response analysis demonstrated higher response rates in patients with low MCM4 expression. Drug sensitivity analysis suggested potential therapeutic drug options based on MCM4 expression. Functional experiments confirmed the oncogenesis effects of MCM4 in SKCM cells. : MCM4 is a potential prognostic biomarker and predictor of immunotherapy response in SKCM patients.
Increasingly evidence shows that the interaction between long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and their downstream target genes plays a pivotal role in the onset and progression of tumors, emerging as a foc...Increasingly evidence shows that the interaction between long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and their downstream target genes plays a pivotal role in the onset and progression of tumors, emerging as a focal point in tumor research. This study sought to assess the biological function of lncRNA SNHG15 and investigate the underlying mechanisms involved in SNHG15/miR-153-3p/KLF5 signal axis in breast cancer (BC). The expressions of SNHG15, miR-153-3p and KLF5 in human BC tissues and cell lines were detected by quantitative real-time PCR and/or western blot. To investigate the biological functions of SNHG15, we knocked it down in BC cells and observed its effects both and . The underlying mechanisms of competitive endogenous RNA (ceRNA) between SNHG15 and miR-153-3p were elucidated through bioinformatics analysis, dual-luciferase reporter assays and rescue experiments. SNHG15 expression was notably elevated in BC tissues and cell lines. Knockdown of SNHG15 significantly reduced the ability of proliferation, migration and invasion in BC cells. miR-153-3p was a direct target of SNHG15, while miR-153-3p mediated the expression of KLF5 in BC cell lines. In addition, the effect of SNHG15 downregulation on the biological behavior of BC cells can be offset by the inhibition of miR-153-3p. Mechanically, SNHG15 may act as the ceRNA of miR-153-3p, thereby regulating the expression of its target gene KLF5. SNHG15 promotes proliferation and metastasis by sponging miR-153-3p and regulates KLF5 expression, suggesting that SNHG15 may be a potential biomarker and therapeutic target for BC.
Polyploid giant cancer cells (PGCCs) play an important role in regulating heterogeneity, growth, and chemotherapy resistance of malignant tumors. Paxillin is a unique cytoskeletal protein and drives persistent migration....Polyploid giant cancer cells (PGCCs) play an important role in regulating heterogeneity, growth, and chemotherapy resistance of malignant tumors. Paxillin is a unique cytoskeletal protein and drives persistent migration. In this study, we investigated the molecular mechanism by which paxillin regulates the invasion and migration of PGCCs with daughter cells (PDCs). We treated HCT116 and LoVo cells with arsenic trioxide (ATO) to induce the formation of PGCCs, and the migration, invasion, and proliferation abilities of PDCs were measured using wound-healing, western blot, immunofluorescence, cell transfection, and dequenching (DQ)-gelatin assays. ATO-induced PDCs had higher invasion, migration, and proliferation ability. Focal adhesion protein paxillin, cytoskeletal protein CDC42, and protease-related protein cathepsin B/D were highly expressed in PDCs. CDC42 promotes the phosphorylation of paxillin by regulating the expression of integrin β1. When phosphorylated at specific tyrosine residues, paxillin plays an important scaffold role in cell adhesion by recruiting structural and signaling molecules (cathepsin B/D) involved in cell movement and migration. Cathepsin B/D can also promote the phosphorylation of paxillin and FAK and promote the invasion and migration of PDCs by degrading the extracellular matrix and inducing cytoskeleton disorders. Paxillin phosphorylation plays an important role in PDCs invasion and migration. Paxillin may be a potential predictor of metastasis and an independent prognostic factor for recurrence and may target phosphorylation to mitigate the impact of chemotherapy-resistant cells on cancer progression, thereby improving patient outcomes.
Hepatocellular carcinoma (HCC) represents a complex malignancy characterized by molecular mechanisms that remain incompletely elucidated, underscoring the necessity for identifying genetic markers. Members of the histone...Hepatocellular carcinoma (HCC) represents a complex malignancy characterized by molecular mechanisms that remain incompletely elucidated, underscoring the necessity for identifying genetic markers. Members of the histone deacetylase (HDAC) family are integral to epigenetic regulation, influencing chromatin architecture and transcriptional activity, thereby modulating gene expression within eukaryotic cells. Dysregulation of HDACs has been implicated in the initiation of aberrant transcriptional programs, contributing to the oncogenesis and progression of various cancers, including HCC. Despite the extensive HDAC family, the specific roles of individual members in HCC are not well-defined. This study utilizes data derived from clinical specimens and comprehensive databases to demonstrate that histone deacetylases, particularly HDAC7, exhibit differential expression in HCC samples, which correlates with significant variations in prognosis and pathological staging. Furthermore, functional enrichment analyses of HDAC7 and its co-expressed genes indicate that HDAC7 may act as an oncogene by modulating the expression of genes associated with key tumorigenic pathways. The analysis of immune cell infiltration further elucidates the association between HDAC7 expression levels and various immune cell types. In summary, HDAC7 emerges as a potential biomarker for the prognosis and diagnosis of HCC, providing significant insights for future research and therapeutic strategies.
The expression pattern and functions of CBX4 in prostate cancers remain ambiguous. This study aims to investigate the performance of CBX4 in prostate cancer progression and preliminary inquiry potential mechanisms. The...The expression pattern and functions of CBX4 in prostate cancers remain ambiguous. This study aims to investigate the performance of CBX4 in prostate cancer progression and preliminary inquiry potential mechanisms. The GEPIA data website was utilized to evaluate the expression patterns of CBX families and their correlations with prognosis. The "clusterprofiler" package was used for GSEA analysis. Seurat and CellChat package were used to analyze the single-cell expression profiles. The RT-qPCR, western blot and IHC staining were performed to detect the expression of CBX4 in prostate cancer tissues or cell lines. The cell functional experiments were performed, including MTT, colony formation assay, Transwell assay and scratch assay. Western blot was conducted to explore the regulation of CBX4 on EMT markers and PI3K/AKT pathway markers. CBX4 was significantly up-regulated at tissue and cell levels in prostate cancer. High expression level of CBX4 was closely associated with advanced stage and poor prognosis. Of note, CBX4 was observed to promote immunosuppressive tumor environment via PDGF, VEGF, WNT signaling by cell-cell communications. experiments confirmed the expression level. Cell function and western blot proved the down-regulation of CBX4 dramatically inhibited the proliferation, invasion and migration of prostate cancer cells by targeting PI3K/AKT signaling. CBX4 might serve as a potential oncogene in prostate cancer progression. This study provides a new target for the treatment of prostate cancer.
Breast cancer is the leading cause of cancer-related mortality among women. Doxorubicin (DOX) is the major chemotherapeutic agent for breast cancer treatment, but its efficacy is hindered by chemoresistance and dose-depe...Breast cancer is the leading cause of cancer-related mortality among women. Doxorubicin (DOX) is the major chemotherapeutic agent for breast cancer treatment, but its efficacy is hindered by chemoresistance and dose-dependent toxicity. Overcoming these challenges requires novel therapeutic strategies that enhance DOX sensitivity while minimizing its adverse effects. Diallyl trisulfide (DATS), a natural organosulfur compound derived from garlic, has demonstrated anticancer potential, yet its role in enhancing DOX chemosensitivity remains unclear. The anticancer potential of the combination treatment was investigated using MTT, glucose uptake, and lactate production assays, Western blot, flow cytometry, TUNEL staining, transfection, and an orthotopic tumor model in NOD/SCID mice. DATS and DOX combination treatment synergistically inhibited the viability of breast cancer cell lines. The combination treatment significantly reduced glucose uptake and lactate production while downregulating key glycolytic regulators, including GLUT1, LDHA, and HIF-1α. These metabolic alterations were associated with enhanced apoptosis, as evidenced by elevated expression of Bax, cleaved caspase-3, and PARP1, along with downregulation of anti-apoptotic proteins Bcl-2 and Bcl-xL. TUNEL and Annexin V-FITC/PI assays further confirmed apoptosis induction in response to combination therapy. studies using an orthotopic MDA-MB-231 xenograft model revealed that DATS and DOX combination treatment significantly suppressed tumor growth while reducing systemic toxicity, as indicated by stable body weight and minimal adverse effects. Overall, our findings show that DATS enhances DOX sensitivity by inhibiting the Warburg effect and promoting apoptosis in breast cancer cells. These findings suggest that the DOX-DATS combination represents a promising strategy to improve chemotherapeutic efficacy in breast cancer.
Breast cancer remains a major global health burden, necessitating improved prognostic markers and therapeutic strategies. This study investigates the role of class II major histocompatibility complex transactivator (CIIT...Breast cancer remains a major global health burden, necessitating improved prognostic markers and therapeutic strategies. This study investigates the role of class II major histocompatibility complex transactivator (CIITA), a master regulator of major histocompatibility complex class II(MHC-II) gene expression, in breast cancer. Although CIITA is well recognized for its role in antigen presentation in immune cells, its function in tumor immunity and prognosis remains underexplored. Through integrative bioinformatics analyses using The Cancer Genome Atlas (TCGA) and other datasets, we demonstrate that high CIITA expression is associated with favorable clinical outcomes and enhanced immune activation in breast cancer. CIITA levels correlate with increased infiltration of antitumor immune cells, elevated expression of immune checkpoint genes, and enrichment of immune-related pathways. Immunohistochemical staining of breast cancer tissues further confirms CIITA protein expression patterns. Moreover, functional enrichment analyses suggest that CIITA may influence tumor-immune interactions by modulating immune response pathways. A prognostic nomogram incorporating CIITA expression shows robust predictive value for overall survival, offering potential clinical utility. These findings highlight CIITA as a promising prognostic biomarker and immunomodulatory target in breast cancer, shedding light on its role in shaping the tumor immune microenvironment.
Triple-negative breast cancer (TNBC) exhibits a higher propensity for recurrence, distant metastasis, and mortality than the other subtypes of breast cancer. TNBC is primarily attributed to the lack of expression of the...Triple-negative breast cancer (TNBC) exhibits a higher propensity for recurrence, distant metastasis, and mortality than the other subtypes of breast cancer. TNBC is primarily attributed to the lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Single-cell sequencing results of CD8 T cells in TNBC patients were screened for differentially expressed and immune-related genes. The selected genes were then analyzed with immunohistochemistry for their prognostic effects. Additionally, a regression model was constructed to ascertain the gene expression score and classify patients into high- and low-risk groups. We further analyzed the impact of gene expression on prognosis based on risk grouping and evaluated its potential as a prognostic predictor for TNBC patients. This analysis was validated using PCR and the prognostic data from patient samples. We also investigated the effect of risk grouping on immunotherapy in TNBC patients and evaluated its potential to predict the efficacy of immunotherapy in TNBC patients. Single-cell sequencing of CD8 T cells from TNBC patients identified 191 differentially expressed genes. Among them, XCL1, RASGRP1, CTSD, and AIP were reported to be independent prognostic factors for TNBC. The results were verified through immunohistochemistry. Additionally, a regression analysis model was constructed using these four genes to classify patients into risk groups. The high-risk group correlated with a poor prognosis in patients and could serve as an independent prognostic factor for TNBC. The results were further validated through PCR. Notably, patients in the low-risk group displayed a better response to immunotherapy. Based on the single-cell sequencing results of CD8 T cells from TNBC patients, a prediction model was established, which facilitated prognosis prediction in TNBC patients and evaluated the patients' response to immunotherapy. In summation, this model could potentially assist in improving the efficacy of TNBC immunotherapy.
Histone H3K14 is a crucial site for histone H3 modifications, which are intimately connected to processes such as DNA replication, gene expression, and transcription. Modifications at H3K14 can lead to damage within the...Histone H3K14 is a crucial site for histone H3 modifications, which are intimately connected to processes such as DNA replication, gene expression, and transcription. Modifications at H3K14 can lead to damage within the human body. Specifically, the acetylation of H3K14 influences immune system function, often linking to conditions like tumor inflammation and immune-related diseases. Lately, H3K14 has garnered significant attention across various scientific disciplines. This review outlines how H3K14 acetylation impacts DNA replication, enhances gene expression, and influences T cell development and activation. Furthermore, the combination of H3K14 acetylation with propionylation and butyration can also stimulate gene expression. In contrast, H3K14 methylation hinders DNA replication, while H3K14 ubiquitination affects both gene expression and transcriptional activity. The review also discusses the regulation of H3K14 by non-coding RNA, histone acetyltransferases, histone deacetylases, nuclear proteins, and pharmaceutical compounds. It explores the relationship between H3K14 and the diagnosis, onset, and treatment of diseases. By doing so, this review aims to offer a fresh perspective for a comprehensive understanding of H3K14's functions.
To investigate the use of heat shock protein 90alpha (HSP90α) as a marker for prognostic evaluation and efficacy monitoring in patients receiving PD-1 inhibitors treatment for advanced gastric cancer (AGC). We investiga...To investigate the use of heat shock protein 90alpha (HSP90α) as a marker for prognostic evaluation and efficacy monitoring in patients receiving PD-1 inhibitors treatment for advanced gastric cancer (AGC). We investigated the value of HSP90α in AGC patients treated with PD-1 inhibitors from a clinical perspective using human plasma samples. In summary, plasma HSP90α was significantly associated with neutrophil-to-lymphocyte (NLR) in AGC patients at baseline. Regarding short-term efficacy, HSP90α levels decreased considerably after PD-1 inhibitor treatment in the partial response (PR) group (P=0.016). Furthermore, there was no significant difference between HSP90α levels in stable disease (SD) group before and after immunotherapy (P=0.659). However, HSP90α levels were considerably greater in AGC patients at disease progression and eventual PD-1 inhibitor therapy failure compared to baseline (P=0.041, P=0.005). Notably, plasma HSP90α, treatment lines, metastatic sites, and NLR level were independent predictive variables for overall survival (OS) in AGC patients receiving PD-1 inhibitors treatment before and after propensity score matching. Additionally, we constructed the nomogram model depending on the above independent prognostic variables, which can well differentiate the clinical prognosis of patients (P<0.001). And ROC curves, calibration curves, and decision curve analysis curves revealed promising discrimination and accuracy of the nomogram. Finally, plasma HSP90α showed specific prognostic value in different subgroups of clinical characteristics. Plasma HSP90α can be used as a marker for efficacy monitoring and prognostic assessment in AGC patients receiving PD-1 inhibitors treatment. We combined plasma HSP90α, NLR, and clinical characteristics to construct a nomogram for predicting the prognosis of gastric cancer immunotherapy, providing a powerful tool for clinical decision-making.
Thyroid cancer, including papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC), exhibits distinct molecular characteristics in adult and pediatric populations. Understanding these differences is vital...Thyroid cancer, including papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC), exhibits distinct molecular characteristics in adult and pediatric populations. Understanding these differences is vital for identifying therapeutic targets and prognostic biomarkers. We performed an integrative multi-omics analysis combining proteomics, phosphoproteomics, metabolomics, and RNA sequencing data from adult and pediatric thyroid cancer cohorts. Differential expression analyses were conducted for all the multi-omics data with false discovery rate adjustments. Enzyme mapping of metabolites was performed using MetaBridge, while cross-omics integration revealed 46 key genes associated with reprogrammed energy metabolism. Clinical relevance was evaluated through survival analyses on cBioPortal and KM plotter platforms, and immunotherapy responses were assessed based on gene expression profiles. The 46 identified genes, primarily involved in mitochondrial energy metabolism and oxidative phosphorylation, were strongly associated with poor disease-free and overall survival in PTC and ATC patients. In ATC, a high tumor mutation burden correlated with worse outcomes, underscoring its prognostic value. Additionally, seven genes (AK2, SUCLG2, NDUFV2, GLUD1, HADHA, ALDH1A1, and NADSYN1) were linked to improved responses to anti-PD-1 immunotherapy, highlighting their potential as biomarkers for treatment stratification. Furthermore, functional studies reveal that AK2 plays a key role in thyroid cancer progression. This study offers critical insights into thyroid cancer biology and provides a foundation for targeted therapies and personalized immunotherapy strategies to improve patient outcomes.
Ovarian cancer (OC), the seventh most common cancer in women globally, is one of the most prevalent and lethal gynecological cancers. With a high degree of malignancy and a dismal prognosis, late-stage patients frequentl...Ovarian cancer (OC), the seventh most common cancer in women globally, is one of the most prevalent and lethal gynecological cancers. With a high degree of malignancy and a dismal prognosis, late-stage patients frequently experience relapses and metastases. Associated with this is the high drug resistance of OC, which is a common challenge in cancer treatment. Natural products have garnered increasing attention in tumor treatment due to their relatively high safety and stable sources. Previous studies have demonstrated that various active ingredients in natural products can impact the progression of OC through diverse molecular mechanisms. These mechanisms include inducing cell cycle arrest, regulating reactive oxygen species (ROS), modulating autophagy, promoting cell apoptosis, inhibiting proliferation, invasion, and migration of OC cells, and regulating the tumor immune microenvironment (TIME). This article comprehensively elucidates the mechanisms by which natural products combat ovarian cancer and highlights both the emerging opportunities and existing challenges in their development as effective therapeutic agents.