TRIM16 E121D variant affects the risk and prognosis of hepatocellular carcinoma by modulating the Wnt/ß-catenin pathway.

TRIM16 has been identified as a tumor suppressor in hepatocellular carcinoma (HCC). This study aimed to investigate whether there are genetic variants in TRIM16 influencing HCC risk and/or prognosis and explore the mechanisms. We performed a gene-wide single-nucleotide polymorphism (SNP) mining in TRIM16. The associations of SNPs with both HCC risk and prognosis were assessed through two independent cohorts respectively. Functional experiments were performed to investigate the underlying mechanisms. A missense variant rs2074890 (G > T, resulting in an amino acid substitution from glutamate to aspartate at code 121, E121D) of TRIM16 was found to be associated with both HCC risk (odds ratio = 0.806, p = 0.023) and prognosis (hazard ratio = 0.44, p = 0.034). Compared to the rs2074890 G allele (corresponding to TRIM16121E ) homozygote carriers, the rs2074890 T allele (corresponding to TRIM16121D ) carriers showed lower HCC risk and better overall survival. Mechanistically, TRIM16121D has stronger ability to inhibit proliferation, migration, and invasion of HCC cells. Furthermore, TRIM16121D could bind to ß-catenin better and mediate K48-linked ubiquitination to degrade ß-catenin, which leads to inhibition of Wnt/ß-catenin pathway. In conclusion, TRIM16 E121D variant impacts both risk and prognosis of HCC via regulation of Wnt/ß-catenin pathway, which may lead to better understanding the pathogenesis of HCC.

Correlation of gene polymorphisms of vascular endothelial growth factor with grade and prognosis of lung cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF) gene is highly polymorphic, and single nucleotide polymorphisms (SNP) of VEGF gene are associate with cancer prognosis. This study aimed to analyze the correlation of VEGF gene polymorphisms with grade and prognosis of lung cancer. METHODS: A total of 458 Chinese patients with primary lung cancer were enrolled from September 2008 to October 2013. The genotypes of -2578C > A, -1154G > A, - 460 T > C, and + 405G > C were analyzed in white blood cells from patients using polymerase chain reaction based restriction fragment length polymorphism. RESULTS: Our data showed that -1154G > A polymorphism was significantly associated with tumor stages, but all four tested VEGF gene polymorphisms had no significant effect on survival. CONCLUSIONS: VEGF polymorphisms may relate to stage of lung cancer in Chinese population.

LINC00673 exerts oncogenic function in cervical cancer by negatively regulating miR-126-5p expression and activates PTEN/PI3K/AKT signaling pathway.

BACKGROUND: Recent studies have indicated the crucial regulator roles of a long non-coding RNA (lncRNA) LINC00673 in cancer pathogenesis and development. However, the clinical significance and functional effects of LINC00673 in cervical cancer remains unknown. METHODS: LINC00673 mRNA expression in cervical cancer tissues was measured by quantitative Real-time PCR (qRT-PCR), and the association between LINC00673 expression and the overall survival (OS) time of patients was analyzed by Kaplan-Meier survival plot. Cell proliferation was assessed using CCK8 assay, Flow cytometry analysis and cell colony formation assay. The association between miR-126-5p and LINC00673 was clarified by Luciferase activity assay. Furthermore, xenografts model in mice in vivo were used to evaluate the effects of LINC00673 expression on tumor growth of cervical cancer. RESULTS: It was confirmed that the relative mRNA expression of LINC00673 was promoted in cervical cancer tissues and cancer cell lines compared with its corresponding normal tissues and cells (P < 0.05). Higher LINC00673 expression was associated with tumor size, lymph node metastasis, and International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.05). Survival analysis showed higher LINC00673 expression predicted poor OS of cervical cancer patients, and Multivariate Cox analysis demonstrated that higher LINC00673 expression was identified as an independent risk factor for OS. LINC00673 overexpression promoted cell proliferation and cell cycle progression, but LINC00673 knockdown inhibited cell proliferation and cell cycle progression significantly (P < 0.05). Besides, overexpression of LINC00673 was negatively correlated with lower miR-126-5p expression in cervical cancer tissues. In vivo xenograft tumor assay indicated that LINC00673 silencing reduced the tumor volume and weight. Bioinformatics analysis revealed that miR-126-5p targeted 3'-UTR of LINC00673, and LINC00673 promoted cell proliferation by sponging to miR-126-5p in cervical cancer cells. Additionally, it was demonstrated that LINC00673 significantly activated the PTEN/PI3K/AKT signaling pathway in cervical cancer cells. CONCLUSION: These results provide the evidence that LINC00673 overexpression promotes cervical cancer cells progression through regulating miR-126-5p and activating the PTEN/PI3K/AKT signaling pathway, indicating that LINC00673 may be a potential therapeutic target for cervical cancer treatment.

HLA Class-II Expression in Human Tumors.

HLA class II molecules play a pivotal role in antigen presentation to T lymphocytes. This chapter analyzed the expression of these molecules in different human tumors and their role in cancer progression. The possible connection between tumor HLA class II expression and the pathogenesis of autoimmune diseases is discussed.

Proliferation genes in lung development associated with the prognosis of lung adenocarcinoma but not squamous cell carcinoma.

There are many similarities between embryonic development and tumorigenesis, and gene expression profiles show that certain correlations exist between the gene signature during development and the clinical phenotypes of different cancers. Our group previously reported the gene expression profiles of human lung development, and the expression of one group of proliferation-related genes (PTN1 genes) steadily decreased during lung development. Here, we examined the prognostic value of PTN1 genes in 5 independent lung adenocarcinoma (ADC) and 5 lung independent squamous cell carcinoma (SCC) microarray datasets and found that the expression levels of PTN1 genes were associated with survival in lung ADC but not lung SCC. All of the lung ADC datasets contained a set of highly correlated genes from PTN1 genes, but the lung SCC datasets had no similar set of genes. We identified 63 unique core genes from the PTN1 genes in the 5 lung ADC datasets: 17 of these core genes appeared in at least 4 of the lung ADC datasets, and the 17 corresponding proteins clearly interacted more strongly with each other in lung ADC than in lung SCC. Moreover, 16 of the 17 core genes play major roles in the G2 /M phase of the cell cycle. These data indicate that proliferation-related genes in lung development have a significant prognostic value for lung ADC; the synergistic effects of the 17 core genes play an important role in lung ADC prognosis. These genes may have significant clinical implications for the treatment and prognosis of lung ADC.

Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer.

BACKGROUND/AIMS: MicroRNAs (miRNAs) or exosomes have recently been shown to play vital regulatory or communication roles in cancer biology. However, the roles and mechanisms of exosomal miRNAs in pancreatic ductal adenocarcinoma (PDAC) remain unknown. We aimed to investigate the detailed roles and mechanisms of tumor-generated exosomal miRNAs in progression of PDAC. METHODS: miR-222 was identified by miRNA microarray studies in exosomes of PDAC cells, and further analyzed in plasma exosomes of PDAC patients. The regulatory mechanisms of miR-222 were explored by qRT-PCR, WB, dual-luciferase assays and immunofluorescence or confocal analysis. Other biological assays include transwell, xenograft models and so on. RESULTS: miR-222 is significantly high in tumor exosomes or highly invasive PDAC cells. miR-222 could directly regulate p27 to promote cell invasion and proliferation. miR-222 could also activate AKT by inhibiting PPP2R2A expression, thus inducing p27 phosphorylation and cytoplasmic p27 expression to promote cell survival, invasion and metastasis. Expressions of miR-222 and p27 were significantly inversely correlated, and cytoplasmic p27, instead of nuclear p27, was associated with tumor malignancy. miR-222 could be transmitted between PDAC cells via exosome communication, and the exosomal miR-222 communication is functional. Plasma exosomal miR-222 in PDAC patients was high and significantly correlated to tumor size and TNM stage, and was an independent risk factor for PDAC patient survival. CONCLUSION: Tumor-generated exosomes could promote invasion and proliferation of neighboring tumor cells via miR-222 transmission, the plasma exosomal miR-222 plays important roles and may be a useful prognostic maker in PDAC.

Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT.

The "integrated diagnosis" for infiltrating gliomas in the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system requires assessment of the tumor for IDH mutations and 1p/19q codeletion. Since TERT promoter mutations and ATRX alterations have been shown to be associated with prognosis, we analyzed whether these tumor markers provide additional prognostic information within each of the five WHO 2016 categories. We used data for 1206 patients from the UCSF Adult Glioma Study, the Mayo Clinic and The Cancer Genome Atlas (TCGA) with infiltrative glioma, grades II-IV for whom tumor status for IDH, 1p/19q codeletion, ATRX, and TERT had been determined. All cases were assigned to one of 5 groups following the WHO 2016 diagnostic criteria based on their morphologic features, and IDH and 1p/19q codeletion status. These groups are: (1) Oligodendroglioma, IDH-mutant and 1p/19q-codeleted; (2) Astrocytoma, IDH-mutant; (3) Glioblastoma, IDH-mutant; (4) Glioblastoma, IDH-wildtype; and (5) Astrocytoma, IDH-wildtype. Within each group, we used univariate and multivariate Cox proportional hazards models to assess associations of overall survival with patient age at diagnosis, grade, and ATRX alteration status and/or TERT promoter mutation status. Among Group 1 IDH-mutant 1p/19q-codeleted oligodendrogliomas, the TERT-WT group had significantly worse overall survival than the TERT-MUT group (HR: 2.72, 95% CI 1.05-7.04, p = 0.04). In both Group 2, IDH-mutant astrocytomas and Group 3, IDH-mutant glioblastomas, neither TERT mutations nor ATRX alterations were significantly associated with survival. Among Group 4, IDH-wildtype glioblastomas, ATRX alterations were associated with favorable outcomes (HR: 0.36, 95% CI 0.17-0.81, p = 0.01). Among Group 5, IDH-wildtype astrocytomas, the TERT-WT group had significantly better overall survival than the TERT-MUT group (HR: 0.48, 95% CI 0.27-0.87), p = 0.02). Thus, we present evidence that in certain WHO 2016 diagnostic groups, testing for TERT promoter mutations or ATRX alterations may provide additional useful prognostic information.

Exploring the potential of the TCR repertoire as a tumor biomarker (Review).

T cells play an important role in adaptive immunity. Mature T cells specifically recognize antigens on major histocompatibility complex molecules through T-cell receptors (TCRs). As the TCR repertoire is highly diverse, its analysis is vital in the assessment of T cells. Advances in sequencing technology have provided convenient methods for further investigation of the TCR repertoire. In the present review, the TCR structure and the mechanisms by which TCRs function in tumor recognition are described. In addition, the potential value of the TCR repertoire in tumor diagnosis is reviewed. Furthermore, the role of the TCR repertoire in tumor immunotherapy is introduced, and the relationships between the TCR repertoire and the effects of different tumor immunotherapies are discussed. Based on the reviewed literature, it may be concluded that the TCR repertoire has the potential to serve as a biomarker for tumor prognosis. However, a wider range of cancer types and more diverse subjects require evaluation in future research to establish the TCR repertoire as a biomarker of tumor immunity.

DPF2 overexpression correlates with immune infiltration and dismal prognosis in hepatocellular carcinoma.

Background: Double plant homeodomain finger 2 (DPF2), belonging to the d4 family of structural domains, has been associated with various human malignancies. However, its impact on hepatocellular carcinoma (HCC) remains unclear. The objective of this study is to elucidate the role of DPF2 in the diagnosis and prognosis of HCC. Methods: DPF2 gene expression in HCC and adjacent tissues was analyzed using Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, validated by immunohistochemical staining of Guangxi specimens and data from the Human Protein Atlas (HPA). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to identify DPF2's potential pathways and functions in HCC. DPF2's mutation and methylation statuses were assessed via cBioPortal and MethSurv. The association between DPF2 and immune infiltration was investigated by TIMER. The prognostic value of DPF2 in HCC was established through Kaplan-Meier and Cox regression analyses. Results: DPF2 levels were significantly higher in HCC than normal tissues (p<0.001), correlating with more severe HCC features (p<0.05). Higher DPF2 expression predicted poorer overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). DPF2 involvement was noted in critical signaling pathways including the cell cycle and Wnt. It also correlated with T helper cells, Th2 cells, and immune checkpoints like CTLA-4, PD-1, and PD-L1. Conclusion: High DPF2 expression, associated with poor HCC prognosis, may disrupt tumor immune balance and promote immune evasion. DPF2 could potentially be utilized as a biomarker for diagnosing and prognosticating hepatocellular carcinoma.

High expression of PDCD11 in colorectal cancer and its correlation with the prognosis and immune cell infiltration.

Objective: To undertake a comprehensive assay of PDCD11 expression in colorectal cancer (CRC) and its association with prognosis and immune cell infiltration (ICIN) utilizing bioinformatics tools. Methods: The PDCD11 expression in CRC and pan-cancer was quantified through datasets from TCGA and GEO databases, and the assay was conducted through R software and the GEPIA database. Moreover, mRNA and protein expression data of PDCD11 were attained from the HPA database. It was attempted to establish protein-protein interaction networks of PDCD11 via the STRING and GeneMANIA databases. The association of PDCD11 expression with CRC staging was evaluated through R software, while its association with CRC and pan-cancer prognosis was figured out via the GEPIA database. Furthermore, the relationship of PDCD11 expression with ICIN was assayed using R software and the TIMER database. Additionally, the influences of PDCD11 knockdown on the proliferation, apoptosis, and migration of colon cancer RKO cell lines was evaluated. Results: PDCD11 exhibited elevated expression in CRC and various other malignancies, potentially indicating a promotive role in cancer progression. Overexpression of PDCD11 was found to correlate with attenuated overall survival in CRC and other malignancies. Moreover, PDCD11 demonstrated promising predictive capabilities for distinguishing between tumor and non-tumor tissues. The positive association of high PDCD11 expression with the infiltration of neutrophils, dendritic cells, CD8+ T cells, CD4+ T cells, and macrophages, as well as with the expression of immune checkpoint molecules CTLA4 and PD-1 was noteworthy. Lentivirus-mediated PDCD11 knockdown suppressed RKO cell proliferation, colony formation, and migration, while triggered apoptosis in these cells. Conclusion: The outcomes unveiled the noticeable function of PDCD11 in CRC and various other malignancies, emphasizing its potential as a prognostic biomarker and therapeutic target.

Solitary fibrous tumor: Can the new Huang risk stratification system for orbital tumors improve prognostic accuracy in other tumor locations?

Solitary fibrous tumors (SFTs) are known for their heterogeneous morphology, characterized by a variety of cell shapes and different growth patterns. They can also arise in various anatomical locations, most commonly in extremities and deep soft tissues. Despite this diversity in morphology and location, all SFTs share a common molecular signature involving the NAB2::STAT6 gene fusion. Due to their unpredictable clinical behavior, establishing prognostic factors is crucial. This study aims to evaluate an orbital risk stratification system (RSS) proposed by Huang et al. for use in extraorbital SFTs using a database of 97 cases. The Huang model takes into consideration tumor size, mitotic figures, Ki-67 index, and dominant constituent cell (DCC) as key variables. Survival analysis confirmed the model's predictive value, with higher-risk scores being associated with poorer outcomes. However, in contrast to the orbital SFTs studied by Huang et al., our study did not find a correlation between tumor size and recurrence in extraorbital cases. While the Huang model performs slightly better than other RSS, it falls short on achieving statistical significance in distinguishing recurrence risk groups in extraorbital locations. In conclusion, this study validates the Huang RSS for use in extraorbital SFTs and underscores the importance of considering DCC, mitotic count, and Ki-67 together. However, we found that including tumor size in this model did not improve prognostic significance in extraorbital SFTs. Despite the benefits of this additional RSS, vigilant monitoring remains essential, even in cases classified as low-risk due to the inherent unpredictability of SFT clinical outcomes.

Comprehensive pan-cancer analysis identifies the RNA-binding protein LRPPRC as a novel prognostic and immune biomarker.

AIMS: RNA-binding proteins (RBPs) play pivotal roles in carcinogenesis and immunotherapy. Leucine-rich pentapeptide repeat-containing protein (LRPPRC) is crucial for RNA polyadenylation, transport, and stability. Although recent studies have suggested LRPPRC's potential role in tumor progression, its significance in tumor prognosis, diagnosis, and immunology remains unclear. MAIN METHODS: We comprehensively analyzed LRPPRC expression in tumors using various databases, including Human Transcriptome Cell Atlas (HTCA), University of California Santa Cruz (UCSC), Human Protein Atlas (HPA), Sangerbox, TISIDB, GeneMANIA, GSCALite, and CellMiner. We examined the correlation between LRPPRC expression level and prognosis, immune infiltration, immunotherapy, methylation, biological function, and drug sensitivity. Single-cell analysis was performed using Tumor Immune Single Cell Hub (TISCH) and CancerSEA software. Patients with acute myeloid leukemia (AML) were categorized based on LRPPRC levels for functional and immune infiltration analyses. The role of LRPPRC in cancer was validated using in vitro experiments. KEY FINDINGS: Our findings revealed that LRPPRC was highly expressed in almost all cancer types, indicating its significant prognostic and diagnostic potential. Notably, LRPPRC was associated with diverse immune features, such as immune cell infiltration, immune checkpoint genes, tumor mutational burden, and microsatellite instability, suggesting its value in guiding immunotherapy strategies. Within AML, the high-expression group had lower levels of immune cells, including CD8+ T cells. In vitro experiments confirmed the inhibitory effects of LRPPRC knockdown on AML cell proliferation. SIGNIFICANCE: This study highlights LRPPRC as a reliable pan-cancer prognostic and immune biomarker, particularly in AML. It lays the groundwork for future research on LRPPRC-targeted cancer therapies.

The role of Cyclin Dependent Kinase Inhibitor 3 (CDKN3) in promoting human tumors: Literature review and pan-cancer analysis.

Background: Although many experiments and clinical studies have proved the link between the expression of CDKN3 and human tumors, we have not been able to identify any bioinformatics study in which the extensive tumor-promoting effect of CDKN3 was systematically analyzed. Objective: Explore the extensive tumor-promoting effects of CDKN3 and review the research progress of CDKN3 in cancer. Methods: We systematically reviewed the literature on CDKN3 and tumors. We explored the potential tumor-promoting effects of CDKN3 on different tumors in the TCGA database and the GTEx database using multiple platforms and websites. We studied the expression level of CDKN3, survival, prognosis, diagnosis, genetic variation, immune infiltration, and enrichment analysis using databases such as TIMER 2.0, GEPIA2, cBioPortal, and STRING. Results: We found that CDKN3 is highly expressed in most tumors. The expression of CDKN3 is closely related to the prognosis of some tumors. And CDKN3 may have diagnostic value. The conclusion of our literature review is roughly the same, but there are differences, which are worthy of further study. Moreover, CDKN3 may be related to immune cell infiltration in tumor tissues. The genetic alteration of LUAD, STAD, SARC, PCPG, and ESCA with "Amplification" as the main type. In addition, through enrichment analysis, we found that CDKN3 affects tumors mainly through the control of the cell cycle and mitosis. Conclusion: CDKN3 is highly expressed in most tumor tissues and has a statistical correlation with survival prognosis. It has extensive tumor-promoting effects that may be related to mechanisms such as immune infiltration.

Peritumor tertiary lymphoid structures are associated with infiltrating neutrophils and inferior prognosis in hepatocellular carcinoma.

BACKGROUND: The positive prediction of prognosis and immunotherapy within tertiary lymphoid structure (TLS) in cancerous tissue has been well demonstrated, including liver cancer. However, the relationship between TLS and prognosis in the peritumoral region of hepatocellular carcinoma (HCC) has received less attention. Few studies on whether TLS, as a typical representative of acquired immune cell groups, is associated with innate immune cells. The aim of this paper was to identify the prognostic role of peritumor TLS in HCC and to simply explore the relationship with neutrophils infiltration. METHODS: This study included cancerous and paracancerous tissue from 170 patients after surgical resection of HCC. TLS was examined and identified by pathological H&E examination, and the impact on prognosis was further classified by determination of total TLS area. Immunohistochemical staining of CD15+ neutrophils was also performed on half of the cases. The obtained results were validated by external public database, as TLS has been widely shown to be tagged with 12 chemokines. RESULTS: In peritumoral tissue, the TLS- group had better overall survival (OS) and disease-free survival (DFS) outcomes compared with the TLS+ group. On the contrary, the intratumor TLS+ group showed better DFS outcomes. When further investigating the relationship between TLS area distribution and DFS, progressively worse prognosis was only found in the peritumor region with increasing TLS density (TLS- vs. TLSL vs. TLSH ). In addition, neutrophil infiltration increased in parallel with TLS density in the peritumoral region, which was not observed in the intratumoral region. CONCLUSIONS: TLS might have a dual prognostic role in different regions of HCC. The abundance of peritumoral TLS is an independent influence of DFS. The inconsistent correlation between neutrophils and corresponding TLS in different regions may indicate different pathways of immune aggregation and may serve as an explanation for the different prognosis of TLS, which needs to be specifically explored.

VNN1 as a potential biomarker for sepsis diagnosis and its implications in immune infiltration and tumor prognosis.

Background: This study explored novel biomarkers for diagnosing sepsis, a severe disease prevalent in clinical settings, particularly threatening to elderly patients. Methods: Using microarray gene expression datasets and fatty acid metabolism signatures, we identified differentially expressed genes between sepsis and healthy control groups. Correlations between candidate genes, immune cells, and immune function were assessed. Logistic regression analysis and single-gene GSEA analysis were performed to identify potential biomarkers. The biomarkers' association with different types of tumors was investigated. Results: Twelve genes related to fatty acid metabolism were excluded. CA4, OLAN, and VNN1 were found relevant to immune cells and function. Among these, only VNN1 showed statistical significance (p < 0.05), with a strong area under the ROC curve (0.995). High VNN1 expression indicated activation of certain metabolic pathways, while low expression suggested potential autoimmune responses. VNN1 was up-regulated in eight tumors and down-regulated in eight others. High VNN1 expression was linked to poor prognosis in six types of tumors, and low expression was linked to poor prognosis in four types of tumors. VNN1 expression showed correlations with stromal scores, immune scores, and cancer purity in different types of tumors. Conclusion: VNN1 holds promise as a potential biomarker for sepsis diagnosis and is significant in identifying immune infiltration in tumor tissue and predicting tumor prognosis.

Clinical Impact of Androgen Receptor-Suppressing miR-146b Expression in Papillary Thyroid Cancer Aggressiveness.

CONTEXT: Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Dysregulated expression of miR-146b and androgen receptor (AR) has been shown to play critical roles in tumorigenesis in PTC. However, the mechanistic and clinical association between AR and miR-146b is not fully understood. OBJECTIVE: The purpose was to investigate miR-146b as the potential AR target miRNA and its involvement in advanced tumor characteristics of PTC. METHODS: Expression of AR and miR-146b were assessed in frozen and formalin-fixed paraffin-embedded tissue samples from PTC and adjacent normal thyroid specimens by quantitative real-time polymerase chain reaction, and their correlation was examined. Human thyroid cancer cell lines BCPAP and TPC-1 were used to evaluate the effect of AR on miR-146b signaling. Chromatin immunoprecipitation (ChIP) assays were performed to determine whether AR binds to the miR-146b promoter region. RESULTS: Pearson correlation analysis confirmed significant inverse correlation between miR-146b and AR expression. Overexpressing AR BCPAP and TPC-1 cells showed relatively lower miR-146b expression. ChIP assay revealed that AR might bind to the androgen receptor element located on the promoter region of miRNA-146b gene, and overexpression of AR suppresses miR-146b-mediated tumor aggressiveness. The low AR/high miR-146b PTC patient group was associated with advanced tumor characteristics, including higher tumor stage, lymph node metastasis, and worse treatment response. CONCLUSION: To sum up, miR-146b is a molecular target of AR transcriptional repression; therefore, AR suppresses miR-146b expression to reduce PTC tumor aggressiveness.

Correlation of Beta2-Glycoprotein I With Tumor Prognosis in Breast Cancer Patients.

BACKGROUND/AIM: Beta2-glycoprotein I (ß2-GPI) is a plasma glycoprotein, which has been implicated in a variety of physiological functions. However, the connection between ß2-GPI and breast cancer is mostly unknown. Breast cancer is a malignant tumor that severely impairs women's health worldwide. The aim of the study was to investigate the role of ß2-GPI in tumor cells of breast cancer patients and its correlation with tumor prognosis. MATERIALS AND METHODS: A total of 125 female patients diagnosed with breast cancer were enrolled in the study. The expression of ß2-GPI in resected breast tissues was determined by immunohistochemistry (IHC) and correlated with clinicopathological variables by the Chi-squared test. The prognostic value of ß2-GPI for overall survival (OS) and disease-free survival (DFS) was determined by Kaplan-Meier estimates and the significance of differences was evaluated by the log-rank test. RESULTS: ß2-GPI staining was predominantly observed in tumor cells of breast cancer patients and significantly correlated with tumor stage and lymph node metastasis of breast cancer. High ß2-GPI expression was significantly correlated with better OS and DFS. Moreover, DFS was found to be significantly better in patients with higher ß2-GPI expression, especially those in the early tumor stage groups. CONCLUSION: High ß2-GPI expression levels in tumor cells of breast cancer patients were independent factors predicting a better OS and DFS. ß2-GPI activation in high-risk patients may be a potential strategy for reducing breast cancer progression.

Predicting Prognosis and Immunotherapy Response in Multiple Cancers Based on the Association of PANoptosis-Related Genes with Tumor Heterogeneity.

PANoptosis is a newly recognized inflammatory pathway for programmed cell death (PCD). It participates in regulating the internal environment, homeostasis, and disease process in various complex ways and plays a crucial role in tumor development, but its mechanism of action is still unclear. In this study, we comprehensively analyzed the expression of 14 PANoptosis-related genes (PANRGs) in 28 types of tumors. Most PANRGs are upregulated in tumors, including Z-DNA binding protein 1 (ZBP1), nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3), caspase (CASP) 1, CASP6, CASP8, PYCARD, FADD, MAP3K7, RNF31, and RBCK1. PANRGs are highly expressed in GBM, LGG, and PAAD, while their levels in ACC are much lower than those in normal tissues. We found that both the CNV and SNV gene sets in BLCA are closely related to survival performance. Subsequently, we conducted clustering and LASSO analysis on each tumor and found that the inhibitory and the stimulating immune checkpoints positively correlate with ZBP1, NLRP3, CASP1, CASP8, and TNFAIP3. The immune infiltration results indicated that KIRC is associated with most infiltrating immune cells. According to the six tumor dryness indicators, PANRGs in LGG show the strongest tumor dryness but have a negative correlation with RNAss. In KIRC, LIHC, and TGCT, most PANRGs play an important role in tumor heterogeneity. Additionally, we analyzed the linear relationship between PANRGs and miRNA and found that MAP3K7 correlates to many miRNAs in most cancers. Finally, we predicted the possible drugs for targeted therapy of the cancers. These data greatly enhance our understanding of the components of cancer and may lead to the discovery of new biomarkers for predicting immunotherapy response and improving the prognosis of cancer patients.

Machine learning was used to predict risk factors for distant metastasis of pancreatic cancer and prognosis analysis.

BACKGROUND: The mechanisms of distant metastasis in pancreatic cancer (PC) have not been elucidated, and this study aimed to explore the risk factors affecting the metastasis and prognosis of metastatic patients and to develop a predictive model. METHOD: Clinical data from patients meeting criteria from 1990 to 2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and two machine learning methods, random forest and support vector machine, combined with logistic regression, were used to explore risk factors influencing distant metastasis and to create nomograms. The performance of the model was validated using calibration curves and ROC curves based on the Shaanxi Provincial People's Hospital cohort. LASSO regression and Cox regression models were used to explore the independent risk factors affecting the prognosis of patients with distant PC metastases. RESULTS: We found that independent risk factors affecting PC distant metastasis were: age, radiotherapy, chemotherapy, T and N; the independent risk factors for patient prognosis were: age, grade, bone metastasis, brain metastasis, lung metastasis, radiotherapy and chemotherapy. CONCLUSION: Together, our study provides a method for risk factors and prognostic assessment for patients with distant PC metastases. The nomogram we developed can be used as a convenient individualized tool to facilitate aid in clinical decision making.

Enzalutamide-induced signatures revealed by epigenetic plasticity using single-cell multi-omics sequencing in prostate cancer.

Prostate cancer is morphologically and molecularly heterogeneous, which poses obstacles for early diagnosis and treatment. Advancements in understanding the heterogeneity of prostate cancer will help navigate through these challenges and ultimately benefit patients. In this study, we integrated single-cell sequencing for transposase-accessible chromatin and whole transcriptome in prostate cancer cell lines, aiming to decode the epigenetic plasticity upon enzalutamide (ENZ) treatment. By comparing the cell populations representing early-treatment response or resistance to the initial tumor cells, we identified seven signature gene sets; they present consistent trends of chromatin closing co-occurred with down-regulated genes during early response and chromatin opening with up-regulated genes upon maintaining drug resistance. In the molecular signatures, we found genes ZNF337, MAPK15, and ESRRG are favorable in progression-free prognosis during early response, while genes CCDC150, CCDC18, and POC1A marked poor prognosis underpinning the pre-existing drug resistance in The Cancer Genome Atlas prostate adenocarcinoma cohort. Ultimately, drug-target analyses nominated combinatory drug candidates to either enhance early-treatment response or potentially overcome ENZ resistance. Together, our integrative, single-cell multi-omics approach in pre-clinical models is effective in identifying informative signatures from complex molecular events, illustrating diverse drug responses in prostate cancer, and invoking novel combinatory drug strategies to inform clinical decision making.