University Of California Santa Cruz Research Articles

Identification of necroptosis-related gene signatures for predicting the prognosis of ovarian cancer

Ovarian cancer (OC) is one of the most prevalent and fatal malignant tumors of the female reproductive system. Our research aimed to develop a prognostic model to assist inclinical treatment decision-making.Utilizing data from The Cancer Genome Atlas (TCGA) and copy number variation (CNV) data from the University of California Santa Cruz (UCSC) database, we conducted analyses of differentially expressed genes (DEGs), gene function, and tumor microenvironment (TME) scores in various clusters of OC samples.Next, we classified participants into low-risk and high-risk groups based on the median risk score, thereby dividing both the training group and the entire group accordingly. Overall survival (OS) was significantly reduced in the high-risk group, and two independent prognostic factors were identified: age and risk score. Additionally, three genes—C-X-C Motif Chemokine Ligand 10 (CXCL10), RELB, and Caspase-3 (CASP3)—emerged as potential candidates for an independent prognostic signature with acceptable prognostic value. In Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, pathways related to immune responses and inflammatory cell chemotaxis were identified. Cellular experiments further validated the reliability and precision of our findings. In conclusion, necroptosis-related genes play critical roles in tumor immunity, and our model introduces a novel strategy for predicting the prognosis of OC patients.

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

AimsRNA-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 methodsWe 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 findingsOur 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. SignificanceThis 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 diagnostic, prognostic, drug sensitivity and ceRNA internet of PPP4R1 in liver hepatocellular carcinoma (LIHC).

Recent studies have reported a role of protein phosphatase 4 regulatory subunit 1 (PPP4R1) in cancer development. However, its expression, diagnostic significance, prognostic value and biological function in liver hepatocellular carcinoma (LIHC) are not known. The expression level of PPP4R1 in pan-cancer was evaluated by analyzing publicly accessible data from the University of California Santa Cruz (UCSC) Xena database. The diagnostic value of PPP4R1 for tumors was assessed using receiver operating characteristic (ROC) curves, whereas the impact of PPP4R1 on tumor prognosis was determined using Kaplan-Meier survival curves, and a prognostic model for LIHC was established using cox regression analysis. In addition, analysis of the correlation between PPP4R1 and anti-cancer drugs using Spearman's correlation coefficient was carried out. Four databases, miRWalk (mRNA-miRNA interactions), MicroT-CDS (mRNA-miRNA interactions), LncBase (miRNA-lncRNA interactions) and Encyclopedia of RNA Interactomes (ENCORI), were used to predict the competitive endogenous RNA (ceRNA) regulatory network of PPP4R1. Finally, the expression of PPP4R1 protein levels was verified using experiments. The findings indicated that the PPP4R1 expression level in cancerous tissues was notably greater than in adjacent tissues (P<0.05). PPP4R1 showed diagnostic significance for 14 tumors based on the ROC curves results area under the curve >0.7. Furthermore, the Kaplan-Meier survival plots demonstrated that PPP4R1 exhibited prognostic significance for all five tumors (P<0.05). According to the cox regression analysis, LIHC patients' prognosis was independently influenced by pathological stage, M stage, and PPP4R1 (P<0.05). The drug sensitivity analysis revealed a positive correlation between the expression level of PPP4R1 and the half maximal inhibitory concentration (IC50) of fludarabine. Additionally, the ceRNA network prediction indicated that the FGD5 antisense RNA 1 (FGD5-AS1)-hsa-miR-22-3p-PPP4R1 ceRNA network could potentially contribute to the progression of LIHC. The experimental results showed that the expression level of PPP4R1 protein was higher in cancer tissues than in paracancerous tissues. PPP4R1 has diagnostic value in most cancers, and high expression of PPP4R1 is associated with poor prognosis, drug resistance and natural killer cell-mediated toxicity, particularly in LIHC. Therefore, PPP4R1 may be a prognostic biomarker and a potential target for immunotherapy in LIHC.

Trackplot: a fast and lightweight R script for epigenomic enrichment plots.

BigWig files serve as essential inputs in epigenomic data visualization. However, current R packages for visualizing these files are limited, slow, and burdened by numerous dependencies. We introducetrackplot, a minimal R script designed for the rapid generation of integrative genomics viewer (IGV) style track plots, profile plots, and heatmaps from bigWig files. This script offers speed, owing to its reliance onbwtool, resulting in performance gains ofseveral magnitudescompared to equivalentpackages.The script is lightweight, requiring only thedata.tableandbwtoolpackages as primary dependencies. Notably, the plots are generated in base R graphics,eliminatingthe need for additional packages.trackplotqueries the University of California Santa Cruz (UCSC) genome browser for gene models thereby enhancing the reproducibility of analyses. The script extends its support to general transfer format (GTF) further enhancing its versatility. This tool addresses the gaps in existing bigWig visualization approaches by offering speed, simplicity, and minimal dependencies, thereby presenting a valuable asset to researchers in the fields of epigenomics. trackplot is implemented in R is made available under MIT license at https://github.com/PoisonAlien/trackplot.

FHIP1A-DT is a potential novel diagnostic, prognostic, and therapeutic biomarker of colorectal cancer: A pan-cancer analysis

BackgroundFHIP1A-DT is a long non-coding RNA (lncRNA) obtained by divergent transcription whose mechanism in pan-cancer and colorectal cancer (CRC) is unclear. We elucidated the molecular mechanism of FHIP1A-DT through bioinformatics analysis and in vitro experiments. MethodsPan-cancer and CRC data were downloaded from the University of California, Santa Cruz (UCSC) Genome Browser and the Cancer Genome Atlas (TCGA). We analyzed FHIP1A-DT expression and its relationship with clinical stage, diagnosis, prognosis, and immunity characteristics in pan-cancer. We also analyzed FHIP1A-DT expression in CRC and explored the relationship between FHIP1A-DT and CRC diagnosis and prognosis. Then, we analyzed the correlation between FHIP1A-DT and drug sensitivity, immune cell infiltration, and the biological processes involved in FHIP1A-DT. The competing endogenous RNA (ceRNA) regulatory network associated with FHIP1A-DT was explored. External validation was conducted using external data sets GSE17538 and GSE39582 and in vitro experiments. ResultsFHIP1A-DT expression was different in pan-cancer and had excellent diagnostic and prognostic capability for pan-cancer. FHIP1A-DT was also related to the pan-cancer tumor mutation burden (TMB), microsatellite instability (MSI), and immune cell content. FHIP1A-DT was downregulated in CRC, where patients with CRC with low FHIP1A-DT expression had a worse prognosis. A nomogram combined with FHIP1A-DT expression demonstrated excellent predictive ability for prognosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that FHIP1A-DT was associated with epigenetic modification and regulated many cancer-related pathways. The ceRNA network demonstrated the potential gene regulation of FHIP1A-DT. FHIP1A-DT was related to many chemotherapeutic drug sensitivities and immune cell infiltration such as CD4 memory resting T cells, monocytes, plasma cells, neutrophils, and M2 macrophages. The FHIP1A-DT expression and prognostic analysis of GSE17538 and GSE39582, and qPCR yielded similar external verification results. ConclusionFHIP1A-DT was a novel CRC-related lncRNA related to CRC diagnosis, prognosis, and treatment sensitivity. It could be used as a significant CRC biomarker in the future.

A prognostic and immune infiltration analysis of ZEB2 in pan-cancer

[Objective] ZEB2 is known to be participated in several cancers, yet there is no comprehensive analysis about its function in pan-cancer. This study aimed to investigate the role ZEB2 plays in pan-cancer. [Methods] The data was downloaded from the University of California Santa Cruz (UCSC) Xena and the Cancer Genome Atlas (TCGA). The mRNA expression status of ZEB2 was studied in the TCGA_GTEx samples, TCGA samples and paired samples in TCGA, respectively, and protein expression status was obtained from the University of Alabama at Birmingham Cancer data analysis Portal (UALCAN). Kaplan-Meier analysis was applied to 33 kinds of tumors in TCGA, then among the cancers that ZEB2 can affect prognosis, clinical correlation analysis and univariate and multivariate Cox regression analysis were performed. Furthermore, to confirm the prognostic value of ZEB2 in cancers, nomogram models were constructed on lung adenocarcinoma (LUAD) and stomach adenocarcinoma (STAD). The relationship between ZEB2 mRNA expression and immune cell infiltrates was determined by tumor immune estimation resource (TIMER2.0). Protein-protein interaction (PPI) networks were constructed by the STRING. Functional enrichment analysis was also performed using the “ClusterProfiler” package. [Results] ZEB2 was expressed in most tumors, either upregulated or downregulated, and correlated with clinical characteristics in a part of tumors. The expression level of ZEB2 was also found to impact the prognosis of tumors. Additionally, ZEB2 expression was significantly related to immune cells infiltration level in tumor microenvironment. [Conclusion] we propose that ZEB2 has the potential to be a prognostic biomarker and a promising target for cancer immunotherapy.

Pan-cancer analysis of G6PD carcinogenesis in human tumors.

Glucose-6-phosphate dehydrogenase (G6PD) is involved in the catalytic pentose phosphate pathway (PPP), which is closely related to energy metabolism. G6PD plays a crucial role in many types of cancer, but the specific molecular mechanisms of G6PD in cancer remain unclear. Therefore, we investigated the potential oncogenic role of G6PD in various tumors based on The Cancer Genome Atlas (TCGA), the cBioPortal datasets, the University of California Santa Cruz (UCSC) Xena browser and the UALCAN-based online tool. G6PD was highly expressed in several cancer tissues (hepatocellular carcinoma, glioma, and breast cancer) compared with normal tissues and was significantly associated with poor prognosis of hepatocellular carcinoma, clear cell renal cell carcinoma, and breast cancer. Promoter methylation levels of G6PD were lower in Bladder Urothelial Carcinoma (BLCA) (P = 2.77e-02), breast invasive carcinoma (BRCA) (P = 1.62e-12), kidney renal clear cell carcinoma (KIRC) (P = 4.23e-02), kidney renal papillary cell carcinoma (KIRP) (P = 2.64e-03), liver hepatocellular carcinoma (LIHC) (P = 1.76e-02), stomach adenocarcinoma (STAD) (P = 3.50e-02), and testicular germ cell tumors (TGCT) (P = 1.62e-12) and higher in prostate adenocarcinoma (PRAD) (P = 1.81e-09) and uterine corpus endometrial carcinoma (UCEC) (P = 2.96e-04) compared with corresponding normal tissue samples. G6PD expression was positively correlated with the infiltration level of immune cells in most tumors, suggesting that G6PD may be involved in tumor immune infiltration. In addition, the functional mechanism of G6PD also involves "Carbon metabolism", "Glycolysis/Gluconeogenesis", "Pentose phosphate pathway", and "Central carbon pathway metabolism in cancer signaling pathway". This pan-cancer study provides a relatively broad understanding of the oncogenic role of G6PD in various tumors and presents a theoretical basis for the development of G6PD inhibitors as therapeutic drugs for multiple cancers.

Family hypercholesterolemia and LDLR mutations in communities of european origin in southern Brazil: a prospective observational cohort study

Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by high levels of circulating low-density lipoprotein (LDL) and premature coronary heart events. A quarter of the population of Southern Brazil is affected by hypercholesterolemia and the region has the highest mortality rates due to cardiovascular disease in the country. The aim of this study was to describe LDLR mutations in European descendants with FH living in Southern Brazil. Ten mL of venous blood were taken from 40 patients and used for DNA extraction and subsequent Polymerase Chain Reaction (PCR). The DNA fragments were sequenced and analyzed and the data obtained were compared to reference values from the University of California Santa Cruz (UCSC) Genome Browser. A total of 15 mutations were identified in 38 patients (95% of the total samples). These mutations were located in exons 11 (P518L) and 15 (D727G) in Italian, Portuguese and Spanish descendants and the *105T&gt;G mutation, still undescribed, should be critically evaluated by means of mRNA alteration studies. The present study demonstrated for the first time the presence of the P518L mutation located in exon 11 of the LDLR gene in European descendants living in southern Brazil. This mutation has a high potential to be pathogenic since it is located in a domain responsible for LDLR release from the endoplasmic reticulum (ER).

Ag-tech, agroecology, and the politics of alternative farming futures: The challenges of bringing together diverse agricultural epistemologies

Agricultural-technology (ag-tech) and agroecology both promise a better farming future. Ag-tech seeks to improve the food system through the development of high-tech tools such as sensors, digital platforms, and robotic harvesters, with many ag-tech start-ups promising to deliver increased agricultural productivity while also enhancing food system sustainability. Agroecology incorporates diverse cropping systems, low external resource inputs, indigenous and farmer knowledge, and is increasingly associated with political calls for a more just food system. Recently, demand has grown for the potentially groundbreaking benefits of their convergence, with the University of California, Santa Cruz (UCSC) attempting just such a union. Building on its combined expertise in engineering and agroecology, as well as a longstanding reputation as a socially progressive institution, university administrators believe that UCSC could produce a unique, socially just form of ag-tech designed for small, low-resource farmers—a rare contribution given ag-tech’s tendency to cater primarily to large-scale agribusiness. This paper examines the complexities of uniting agroecology and ag-tech through interviews with agroecologists, engineers, and social scientists involved in UCSC’s ag-tech initiative. Within the setting of a historically radical yet neoliberalizing university, I find that significant epistemic and structural barriers exist for agroecology and ag-tech to come together on an even playing field. This case study contributes to broader discussions of the future of food and farming by focusing on the contours and challenges of a widely called-for agricultural collaboration, highlighting its difficulty but also areas of possibility in a particularly rich, contested context.

Pan-cancer analysis of PCAT6 and its effect on oesophageal squamous cell carcinoma cell proliferation and migration

Bioinformatics methods were used to analyze the role of PCAT6 in a variety of tumors and verify its role in oesophageal squamous cell carcinoma (ESCC) EC109 cells. The pan-cancer dataset was downloaded from the University of California Santa Cruz (UCSC) database to analyze the expression of PCAT6 in pan-cancer and its relationship with prognosis, clinical features, and immune infiltration. The expression and prognosis of PCAT6 in ESCC were verified by Gene Expression Omnibus (GEO) and Kaplan-Meier database. CCK8, colony formation, wound healing, Transwell cell invasion (CI), and cell migration (CM) assays were used to detect the effect of PCAT6 knockdown on the ability of ESCC cell proliferation (CP), CI and CM. Gene Set Enrichment Analysis was used to analyze the signaling pathways involved in the regulation of PCAT6. Quantitative real-time PCR and western blotting were used to examine the expression of cancer stem cell-related markers and the activation of JAK/STAT pathway in ESCC after PCAT6 knockdown. PCAT6 is significantly up-regulated in a variety of tumor tissues, and its expression is closely related to prognosis, clinical features and immune infiltration. High expression of PCAT6 leads to poor prognosis in ESCC patients. In ESCC EC109 cells, PCAT6 knockdown inhibited the ability of CP, CI, CM, and stemness, and inhibited the activation of JAK/STAT signaling pathway. PCAT6 expression is elevated in a variety of tumors. PCAT6 plays an oncogene role in ESCC by activating the JAK/STAT signaling pathway.

Systematic pan-cancer analysis of the potential tumor diagnosis and prognosis biomarker P4HA3.

Purpose: Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) is implicated in several cancers' development. However, P4HA3 has not been reported in other cancers, and the exact mechanism of action is currently unknown. Materials and methods: First, the expression profile of P4HA3 was analyzed using a combination of the University of California Santa Cruz (UCSC) database, Cancer Cell Line Encyclopedia (CCLE) database, and Genotype-Tissue Expression (GTEx) database. UniCox and Kaplan-Meier were used to analyze the predictive value of P4HA3. The expression of P4HA3 was analyzed in clinical staging, immune subtypes, and Molecular subtypes. Secondly, the correlation of P4HA3 with immunomodulatory genes, immune checkpoint genes, RNA modification genes, immune cell infiltration, cancer-related functional status, tumor stemness index, DNA mismatch repair (MMR) genes and DNA Methyltransferase was examined. The role of P4HA3 in DNA methylation, copy number variation (CNV), mutational status, tumor mutational burden (TMB), and microsatellite instability (MSI) was also analyzed. In addition, gene set enrichment analysis (GSEA) was used to explore the potential functional mechanisms of P4HA3 in pan-cancer. Finally, P4HA3-related drugs were searched in CellMiner, Genomics of Drug Sensitivity in Cancer (GDSC), and Cancer Therapeutics Response Portal (CTRP) databases. Results: P4HA3 is significantly overexpressed in most cancers and is associated with poor prognosis. P4HA3 is strongly associated with clinical cancer stage, immune subtypes, molecular subtypes, immune regulatory genes, immune checkpoint genes, RNA modifier genes, immune cell infiltration, cancer-related functional status, tumor stemness index, MMR Gene, DNA Methyltransferase, DNA methylation, CNV, mutational status, TMB, and MSI are closely related. Available enrichment analysis revealed that P4HA3 is associated with the epithelial-mesenchymal transition and immune-related pathways. There are currently 20 drugs associated with P4HA3. Conclusion: In human pan-cancer, P4HA3 is associated with poor patient prognosis and multiple immune cells and may be a novel immunotherapeutic target. It may act on tumor progression through the epithelial-mesenchymal transition (EMT) pathway.

Decreased DIO3OS Expression Predicts Poor Prognosis in Hepatocellular Carcinoma and is Associated with Immune Infiltration.

Hepatocellular carcinoma has become one of the most shared cancers in the whole world because of its high morbidity, poor survival rate, and low recovery rate. LncRNA DIO3 opposite strand upstream RNA (DIO3OS) has been reported to be obviously important in several human cancers, while its biological function in hepatocellular carcinoma (HCC) remains unclear. Here, DIO3OS gene expression data and clinical information of HCC patients were extracted from the Cancer Genome Atlas (TCGA) database and the university of California Santa Cruz (UCSC) Xena database. In our study, the Wilcoxon rank sum test was used to compare DIO3OS expression between healthy individuals and HCC patients. It was found that patients with HCC had significantly lower DIO3OS expression than healthy individuals. Furthermore, Kaplan-Meier curves and Cox regression analysis showed that high DIO3OS expression tended to predict better prognosis and higher survival rate in HCC patients. In addition, the gene set enrichment analysis (GSEA) assay was used to annotate the biological function of DIO3OS. It was found that DIO3OS was significantly correlated with immune invasion in HCC. This was also aided by the subsequent ESTIMATE assay. Our study provides a novel biomarker and therapeutic strategy for patients with hepatocellular carcinoma.

An integrative analysis revealing cuproptosis-related lncRNAs signature as a novel prognostic biomarker in hepatocellular carcinoma.

Background: Cuproptosis is a newly defined form of cell death, whether cuproptosis involved in hepatocellular carcinoma (HCC) remains elusive. Method: We obtained patients' RNA expression data and follow-up information from University of California Santa Cruz (UCSC) and The Cancer Genome Atlas (TCGA). We analyzed the mRNA level of Cuproptosis-related genes (CRGs) and performed univariate Cox analysis. Liver hepatocellular carcinoma (LIHC) was chosen for further investigation. Real-Time quantitative PCR (RT-qPCR), Western blotting (WB), Immunohistochemical (IHC), and Transwell assays were used to determine expression patterns and functions of CRGs in LIHC. Next, we identified CRGs-related lncRNAs (CRLs) and differentially expressed CRLs between HCC and normal cases. Univariate Cox analysis, least absolute shrinkage selection operator (LASSO) analysis and Cox regression analysis were used to construct the prognostic model. Univariate and multivariate Cox analysis was used to assess whether the risk model can act as an independent risk factor of overall survival duration. Different risk groups performed immune correlation analysis, tumor mutation burden (TMB), and Gene Set Enrichment Analysis (GSEA) analysis were performed in different risk groups. Finally, we assessed the performance of the predictive model in drug sensitivity. Results: CRGs expression levels have significant differences between tumor and normal tissues. High expression of Dihydrolipoamide S-Acetyltransferase (DLAT) correlated to metastasis of HCC cells and indicated poor prognosis for HCC patients. Our prognostic model consisted of four cuproptosis-related lncRNA (AC011476.3, AC026412.3, NRAV, MKLN1-AS). The prognostic model performed well in predicting survival rates. The results from Cox regression analysis suggested that risk score can serve as an independent prognostic element for survival durations. Survival analysis revealed that low risk patients have extended survival periods compared with those with high risk. The results of the immune analysis indicated that risk score has a positive correlation with B cell and CD4+ T cell Th2, while has a negative relationship with endothelial cell and hematopoietic cells. Besides, immune checkpoint genes have higher expression folds in the high-risk set than in the low-risk set. The high-risk group had higher rates of genetic mutation than the low-risk set while having a shorter survival time. GSEA revealed the signaling pathways enriched in the high-risk group were mostly immune-related, while metabolic-related pathways were enriched in the low-risk group. Drugs sensitivity analysis indicated that our model has the ability to predict the efficacy of clinical treatment. Conclusion: The Cuproptosis-related lncRNAs prognostic formula is a novel predictor of HCC patients' prognosis and drug sensitivity.

Hsa_circ_0072309 is a prognostic biomarker and is correlated with immune infiltration in gastric cancer

BackgroundHsa_circ_0072309 has been identified as a tumor suppressor in several carcinomas. However, its precise role in gastric cancer (GC) remains largely unknown. This study was aimed to explore the precise role of Hsa_circ_0072309 in GC. MethodsThe transcriptional and clinical data of stomach adenocarcinoma were downloaded using the University of California SantaCruz (UCSC) Xena browser. The circular RNA (circRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database. The expression profile and survival analysis of differentially expressed micro RNAs (DEMIs) and differentially expressed messenger RNAs (DEMs) were performed. Correlations between the expression and immune infiltration of the DEMS were studied. Additionally, the expression of hsa_circ_0072309 in GC tissues and cell lines were validated, and the relationship between its expression and clinical features was investigated. Gain- and loss-of function experiments and molecular interaction experiments were also conducted. ResultsOverall, 7 differentially expressed circRNAs, 13 DEMIs, and 17 DEMs were screened. Two DEMIs (hsa_miR-34a-3p and hsa_miR-326) and five DEMs (C7, MARCKSL1, UBE2T, OLR1, and HOXC11) showed significant differences in the high- and low-risk groups. The most significantly enriched Gene Ontology terms were the circadian regulation of gene expression and protein binding. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were the PI3K-Akt and Ras signal pathways. Additionally, six genes were significantly correlated with immune infiltration. The real-time quantitative PCR (RT-qPCR) results revealed a significant downregulation of hsa_circ_0072309 in GC tissues related to tumor size, vascular invasion, and lymph node metastasis. A hsa_circ_0072309 overexpression suppressed whereas a hsa_circ_0072309 knockdown promoted GC cells proliferation and migration in vitro; in addition, hsa_circ_0072309 could directly bind to has-miR-34a-3p and has-miR-330-5p. ConclusionsHsa_circ_0072309 is a potential diagnostic biomarker for GC, and complement component 7 may be a tumor suppressor. These may potentially predict the prognosis of patients with GC and may become new therapeutic targets.

EXOC3L1: A Novel Prognostic Biomarker Correlated with Immune Infiltration in Esophageal Squamous Cell Carcinoma.

BACKGROUND Exocyst complex component 3-like 1 (EXOC3L1) is ubiquitously present in multiple organs. However, its role in esophageal squamous cell carcinoma (ESCC) remains unknown. The aim of this study was to explore the relationship between EXOC3L1 and ESCC. MATERIAL AND METHODS A total of 652 normal samples and 82 ESCC samples obtained from the University of California Santa Cruz (UCSC) Xena were applied to detect the expression difference of EXOC3L1. GSE53625 with 179 paired samples and GSE161533 with 28 paired samples were used for validation. The correlation between clinicopathological features and EXOC3L1 expression was calculated. Kaplan-Meier method was employed to assess the prognostic value of EXOC3L1 in ESCC. Univariate and multivariate Cox regression analyses were carried out to screen the factors contributing to the prognosis of ESCC. In addition, functional enrichment analysis, protein-protein interaction (PPI) network analysis, and immune infiltration analysis were conducted to identify the significantly involved functions of EXOC3L1. RESULTS EXOC3L1 was significantly overexpressed in ESCC compared to normal samples. High expression of EXOC3L1 was associated with worse prognosis, and univariate and multivariate Cox regression analysis demonstrated that EXOC3L1 was an independent prognostic predictor of ESCC. Functional enrichment analysis and immune infiltration analysis disclosed that the expression of EXOC3L1 was correlated with the abundance of several types of immune cells. CONCLUSIONS EXOC3L1 plays a crucial role in the prognosis of ESCC, and it may serve as a reliable biomarker for predicting the survival and a potential therapeutic target for ESCC.

Building a Community Archive: Preserving and Uplifting Stories of Filipino Labor and Migration

Abstract: In April 2022, Watsonville Is in the Heart (WIITH), a research initiative based at the University of California, Santa Cruz (UCSC), launched a new digital archive that preserves histories of Filipino American migration, labor, and community in the Pajaro Valley region of California’s Central Coast. This article describes WIITH’s partnership between UCSC, The Tobera Project, and the descendants of the first Filipinos to settle in the Pajaro Valley. It outlines our methods for critical community-engaged archiving. It also shares the multiple ways in which the WIITH Digital Archive has significantly impacted project stakeholders in the university and the community.

Upregulation of the ZWINT expression correlates with prostate cancer progression and immune infiltration

Prostate cancer (PCa), the most prevalent epithelial malignant neoplasm in the male group globally, is the fifth largest cause of cancer-related death in males. ZW10 Interactor (ZWINT) is involved in the chromosome segregation process, which is linked to the formation of several tumor cells. However, its function in PCa remains unknown. Therefore, our aim was to explore the potential mechanisms of ZWINT in PCa progression. We obtained RNA-seq as well as clinical data from The Cancer Genome Atlas Program (TCGA), University of California Santa Cruz (UCSC) database. Assessment of ZWINT expression in clinical subgroups, immune infiltration, and prognostic relevance using the R program. Search Tool for Recurring Instances of Neighbouring Genes (STRING) tool was applied to construct a ZWINT co-expression network and the potential biological functions involved in differentially expressed genes (DEGs) were investigated by enrichment analysis. ZWINT was upregulated in prostate cancer tissues and showed to be significantly associated with T stage, N stages, Gleason score (GS), and prognosis of prostate cancer patients. Functional enrichment analysis revealed that ZWINT-related genes were mainly related to cell cycle, meiosis, myogenic fiber synthesis, and muscle contraction. In addition, High-expression of ZWINT may have possessed immunosuppressive effects through adverse regulation of several immune cells and factors. ZWINT is overexpressed in prostate cancer and correlated with immune infiltration, which is expected to be a potential biomarker for PCa prognosis.

Expression, tumor immune infiltration, and prognostic impact of HMGs in gastric cancer.

In the past decade, considerable research efforts on gastric cancer (GC) have been expended, however, little advancement has been made owing to the lack of effective biomarkers and treatment options. Herein, we aimed to examine the levels of expression, mutations, and clinical relevance of HMGs in GC to provide sufficient scientific evidence for clinical decision-making and risk management. GC samples were obtained from The Cancer Genome Atlas (TCGA). University of California Santa Cruz (UCSC) XENA, Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, cBioPortal, GeneMANIA, STRING, LinkedOmics, and DAVID databases were employed. The "ggplot2" package in the R software (×64 3.6.3) was used to thoroughly analyze the effects of HMGs. qRT-PCR was performed to assess HMG levels in GC cell lines. A total of 375 GC tissues and 32 paraneoplastic tissues were analyzed. The levels of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN1, HMGN2, and HMGN4 expression were increased in GC tissues relative to normal gastric tissues. HMGA1, HMGA2, HMGB1, HMGB2, and HMGB3 were highly expressed in GC cell lines. The OS was significantly different in the group showing low expressions of HMGA1, HMGA2, HMGB1, HMGB2, HMGB3, HMGN2, HMGN3, and HMGN5. There was a significant difference in RFS between the groups with low HMGA2, HMGB3, and high HMGN2 expression. The levels of HMGA2, HMGB3, and HMGN1 had a higher accuracy for prediction to distinguish GC from normal tissues (AUC value > 0.9). HMGs were tightly associated with immune infiltration and tumor immune escape and antitumor immunity most likely participates in HMG-mediated oncogenesis in GC. GO and KEGG enrichment analyses showed that HMGs played a vital role in the cell cycle pathway. Our results strongly suggest a vital role of HMGs in GC. HMGA2 and HMGB3 could be potential markers for prognostic prediction and treatment targets for GC by interrupting the cell cycle pathway. Our findings might provide renewed perspectives for the selection of prognostic biomarkers among HMGs in GC and may contribute to the determination of the optimal strategy for the treatment of these patients.

A comprehensive prognostic and immune infiltration analysis of EXOC3L1 in pan-cancer.

Exocyst complex component 3 like 1 (EXOC3L1) is widely present in various human tissues, which mainly regulates insulin secretion. However, its roles in tumors remain unclear. In the present study, we aimed to investigate the roles of EXOC3L1 in pan-cancer, and the data was downloaded from of the University of California Santa Cruz (UCSC) Xena and the Cancer Genome Atlas (TCGA). The expression status of EXOC3L1 was studied in the TCGA_GTEx samples, TCGA samples and paired samples in TCGA, respectively. Subsequently, Kaplan-Meier analysis was applied to 33 kinds of tumors in TCGA, among the cancers that EXOC3L1 can affect prognosis, clinical correlation analysis and univariate Cox regression analysis were performed. Furthermore, representative cancers kidney renal clear cell carcinoma (KIRC) and lung squamous cell carcinoma (LUSC) with a sample size larger than 500 were selected to construct nomogram models to confirm the prognostic value of EXOC3L1 in cancers. Additionally, the associations of EXOC3L1 with immune cell infiltrations were performed as well. Mechanistically, functional enrichment analysis was performed to explore potential signaling pathways that EXOC3L1 may involve in. Our study found that EXOC3L1 was differentially expressed in a variety of tumors and was associated with the clinical outcomes and immune microenvironment of several tumors, it may affect the occurrence and development of tumors through NOTCH signaling pathway, PI3K-AKT signaling pathway and immune-related pathways. In conclusion, we propose that EXOC3L1 may serve as a potential prognostic biomarker and a promising target for cancer immunotherapy in a variety of cancers.

Ficolin-2: A potential immune-related therapeutic target with low expression in liver cancer

This study aimed to investigate the role of ficolin-2 (FCN2) in the development and course of hepatocellular carcinoma (HCC) and to contribute to the evolution of innovative HCC therapeutics. Oncomine, GEPIA (Gene Expression Profiling Interactive Analysis), TISIDB (Tumor Immune System Interactions and Drug Bank database), UALCAN (University of Alabama at Birmingham Cancer data analysis portal), UCSC (University of California, Santa Cruz), R package, the Kaplan-Meier technique, Cox regression analysis, LinkedOmics, Pearson's correlation, and a nomogram were used to investigate the prognostic value of FCN2 in HCC. Co-expressed genes were screened. A protein-protein interaction network was created using the STRING database. Finally, immunohistochemistry was performed to establish the expression of FCN2 in HCC tissues. A pan-cancer study centered on HCC-related molecular analysis was also conducted to look for a link between FCN2 and immune infiltration, immune modulators, and chemokine receptors. In HCC tissues, the expression of FCN2 was observed to be lower than that in normal tissues. This was connected to the HCC marker alpha-fetoprotein, showing that FCN2 is involved in the development and progression of cancer. FCN2 may act through Staphylococcus aureus infection, lectins, and other pathways. Furthermore, at the immune level, the expression of FCN2 in HCC was associated with some immune cell infiltration, immunomodulators, and chemokine receptors. FCN2 may be an immune checkpoint inhibitor for HCC, creating a breakthrough in the treatment of HCC.