University Of California Santa Cruz Research Articles

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.

Identification of key genes associated with cancer stem cell characteristics in Wilms’ tumor based on bioinformatics analysis

Nephroblastoma, also known as Wilms' tumor (WT), remains one of the major causes of tumor-related deaths worldwide in children. Cancer stem cells (CSCs) are considered to be the main culprits in cancer resistance and disease recurrence, which are reported in multiple types of tumors. However, the research on CSCs in WT is limited. Therefore, our study aimed to identify the key genes related to CSCs in WT to provide new ideas for treating WT. The RNA-seq and clinical data of WT samples were obtained from the University of California Santa Cruz (UCSC) Xena database, which included 120 WT and six para-cancerous tissues. The mRNA stemness index (mRNAsi) based on mRNA expression was calculated to evaluate tumor stem cell characteristics in WT patients. A Kaplan-Meier (KM) analysis was performed to explore the clinical characteristics of the mRNAsi in WT. A weighted gene co-expression network analysis (WGCNA) was used to identify the key modules and genes related to the mRNAsi. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed to explore the signaling pathways based on the key genes. The expression levels of the key genes were validated by the Gene Expression Omnibus (GEO) database. Further, the important upstream genes were identified by DisNor and gene co-expression analyses. The mRNAsi was significantly upregulated in WT (P=7.2e-05) and showed an upward trend in line with the pathological stage. Patients with lower mRNAsi scores had better overall survival (OS) than those with higher mRNAsi scores (P=0.0087). Eleven genes were defined as the key genes associated with the mRNAsi based on our WGCNA analysis [cor.MM (correlation. Module membership) >0.8 and cor.GS (correlation. Gene significance) >0.45] and were closely related to cell proliferation-related signaling pathways (P<0.05). Moreover, using protein interaction analysis, we identified ATM and CDKN1A as the key upstream regulatory genes of the 11 key genes. Our study showed that the mRNAsi score was a potential prognostic factors in WT and identified the upstream genes ATM and CDKN1A and 11 genes closely related to the mRNAsi, which may provide new insights for CSC-targeted therapy in WT and improve clinical outcomes for WT patients.

Flexible drought deciduousness in a neotropical understory herb.

PremiseAdaptive divergence across environmental gradients is a key driver of speciation. Precipitation seasonality gradients are common in the tropics, yet drought adaptation is nearly unexplored in neotropical understory herbs. Here, we examined two recently diverged neotropical spiral gingers, one adapted to seasonal drought and one reliant on perennial water, to uncover the basis of drought adaptation.MethodsWe combined ecophysiological trait measurements in the field and greenhouse with experimental and observational assessments of real‐time drought response to determine how Costus villosissimus (Costaceae) differs from C. allenii to achieve drought adaptation.ResultsWe found that drought‐adapted C. villosissimus has several characteristics indicating flexible dehydration avoidance via semi‐drought‐deciduousness and a fast economic strategy. Although the two species do not differ in water‐use efficiency, C. villosissimus has a more rapid growth rate, lower leaf mass per area, lower stem density, higher leaf nitrogen, and a strong trend of greater light‐saturated photosynthetic rates. These fast economic strategy traits align with both field‐based observations and experimental dry‐down results. During drought, C. villosissimus displays facultative drought‐deciduousness, losing lower leaves during the dry season and rapidly growing new leaves in the wet season.ConclusionsWe revealed a drought adaptation strategy that has not, to our knowledge, previously been documented in tropical herbs. This divergent drought adaptation evolved recently and is an important component of reproductive isolation between C. villosissimus and C. allenii, indicating that adaptive shifts to survive seasonal drought may be an underappreciated axis of neotropical understory plant diversification.

An integrated pan-cancer analysis of identifying biomarkers about the EGR family genes in human carcinomas

BackgroundThe early growth response (EGR) family genes, including EGR1, EGR2, EGR3 and EGR4, play important roles in transcriptional regulation and have been reported to be involved in the process of cell growth and apoptosis in a variety of human tumors. However, there have been no systematic pan-cancer analysis about EGR family genes. ObjectiveThis study is to clarify the functions and roles of EGR family genes in human pan-cancer. MethodBased on the cancer genome atlas (TCGA) datasets, the University of California Santa Cruz (UCSC) database and several comprehensive bioinformatics methods, we evaluated the expression levels and prognostic values of EGR family genes and explored their relationships with tumor microenvironment (TME), tumor mutation burden (TMB), microsatellite instability (MSI), immune infiltration and immunohistochemistry (IHC). ResultIt was found that the expressions of EGR1, EGR2 and EGR3 were abnormally low in 15 cancers, 11 cancers and 13 cancers, respectively, while the expression of EGR4 was abnormally high in 9 cancers and abnormally low in 5 cancers, compared with the corresponding control samples. The expressions of EGR family genes were significantly associated with prognosis, immune score, stromal score, MSI, TMB and immune infiltration for multiple cancers. Moreover, immunohistochemical results manifested that the protein expressions of EGR1 and EGR3 might cause clinical tumor progression in some cancers. ConclusionThese findings elucidated the important roles of the EGR family genes in tumor development and provided clues for further study of the EGR family genes as potential biomarkers in pan-cancer.

An ultra-fast low-noise preamplifier for Low Gain Avalanche Detectors

The Low Gain Avalanche Detector (LGAD) is a novel Silicon detector with precise timing and fast response. To study the transient response of LGADs, we need to obtain the detector signal using Transient Current Technique (TCT), for which a preamplifier with high bandwidth and low noise is required. Currently, the most widely used preamplifier board in the LGAD community is developed by University of California, Santa Cruz (UCSC). In this paper, we will introduce a newly designed LGAD preamplifier board. Compared with the UCSC board, the performance has been fully improved. The board contains a transimpedance amplifier and two-stage voltage amplifiers. The total charge gain of our preamplifier reaches 20.58 mV ns/fC, with good linearity in the input dynamic range of [0.7 fC, 66 fC]. The −3-dB bandwidth is about 870 MHz, meeting the demands of LGAD amplification. We conducted 90Sr β-scope tests using our preamplifiers and HPK 3.1 single sensors. The equivalent noise charge at 20 °C is 0.27 fC. The jitter contributed by our preamplifier is about 7.12 ps. The results show that our single-channel preamplifier has lower noise and better time resolution than the UCSC boards. Besides, a 9-channel preamplifier board is developed for multi-pad LGAD readout. All channels have good uniformity and low noise. Our preamplifier boards can be well applied in β-scope or laser-scanning TCT tests of LGADs.

Predicting Parkinson disease related genes based on PyFeat and gradient boosted decision tree

Identifying genes related to Parkinson’s disease (PD) is an active research topic in biomedical analysis, which plays a critical role in diagnosis and treatment. Recently, many studies have proposed different techniques for predicting disease-related genes. However, a few of these techniques are designed or developed for PD gene prediction. Most of these PD techniques are developed to identify only protein genes and discard long noncoding (lncRNA) genes, which play an essential role in biological processes and the transformation and development of diseases. This paper proposes a novel prediction system to identify protein and lncRNA genes related to PD that can aid in an early diagnosis. First, we preprocessed the genes into DNA FASTA sequences from the University of California Santa Cruz (UCSC) genome browser and removed the redundancies. Second, we extracted some significant features of DNA FASTA sequences using the PyFeat method with the AdaBoost as feature selection. These selected features achieved promising results compared with extracted features from some state-of-the-art feature extraction techniques. Finally, the features were fed to the gradient-boosted decision tree (GBDT) to diagnose different tested cases. Seven performance metrics were used to evaluate the performance of the proposed system. The proposed system achieved an average accuracy of 78.6%, the area under the curve equals 84.5%, the area under precision-recall (AUPR) equals 85.3%, F1-score equals 78.3%, Matthews correlation coefficient (MCC) equals 0.575, sensitivity (SEN) equals 77.1%, and specificity (SPC) equals 80.2%. The experiments demonstrate promising results compared with other systems. The predicted top-rank protein and lncRNA genes are verified based on a literature review.

CTHRC1 is a Potential Prognostic Biomarker and Correlated with Macrophage Infiltration in Breast Cancer.

BackgroundTumor immune cell infiltration is closely associated with the occurrence and development of tumors. Collagen triple helix repeats containing 1 (CTHRC1), a regulator of collagen expression and cell migration, is involved in the metastasis and invasion of tumors. However, the role of CTHRC1 in breast cancer remains unclear. This study aimed to investigate the prognostic value of CTHRC1, and further explore its association with immune infiltration in breast cancer.MethodsCTHRC1 expression pattern and prognostic value were analyzed using ONCOMINE, PrognoScan, GEPIA, and Kaplan–Meier Plotter databases. We then detected CTHRC1 mRNA levels in breast cancer tissues and paired normal breast tissues by Q-PCR. Subsequently, the University of California Santa Cruz (UCSC) database was used to determine the methylation status of CTHRC1. Furthermore, CTHRC1 mutations were investigated using the Catalogue of Somatic mutations in Cancer (COSMIC) and cBioPortal databases. We also assessed the correlation between CTHRC1 expression and immune cell infiltration using TIMER. In addition, The relationship of CTHRC1 expression with the immune marker sets of various immune cells was evaluated using GEPIA and TIMER.ResultsCTHRC1 was highly expressed in a variety of tumors, including breast cancer. Elevated CTHRC1 expression was related to a poor prognosis. Notably, CTHRC1 expression was significantly associated with macrophage infiltration, especially the immune infiltration gene marker set of M2. Copy number variations, DNA mutations and methylation states might be potential mechanisms for regulating CTHRC1 expression. Protein digestion and absorption, human papillomavirus infection, ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways were identified as the potential CTHRC1-driven signaling pathways.ConclusionThese findings suggest that CTHRC1 could be a promising immune-related biomarker for the treatment of breast cancer patients.

A Pyroptosis-Related Gene Signature Associated with Prognosis and Tumor Immune Microenvironment in Gliomas

BackgroundPyroptosis is a novel form of cell death that plays a significant role in cancer, while the prognostic values of pyroptosis-related genes in gliomas have not been revealed.MethodsWe analyzed the RNA-seq and clinical data of gliomas from the University of California Santa Cruz (UCSC) Xena database to determine differentially expressed pyroptosis-related genes. Based on these genes, a pyroptosis genes signature was constructed after univariate Cox analysis and Lasso Cox analyses. The sensitivity and specificity of pyroptosis genes signature were verified by the Chinese Glioma Genome Atlas (CGGA) dataset. Finally, we explored the association of risk signatures with tumor microenvironment and immune cell infiltration.ResultsOf 15 differentially expressed pyroptosis-related genes, three genes of BCL2 associated X (BAX), caspase 3 (CASP3), and caspase 4 (CASP4) were used to construct the risk signature. The effectiveness of risk signature for predicting survival at 1, 3, 5 years was performed by the receiver operating characteristic curve (ROC), and the area under curves (AUC) was 0.739, 0.817, and 0.800, respectively. Functional enrichment results showed signal transduction, cell adhesion, immune response, and inflammatory response were enriched. The immune analysis revealed that pyroptosis had a remarkable effect on the immune microenvironment.ConclusionIn this study, we constructed a pyroptosis-related gene signature, which can serve as a potential biomarker for predicting the survival of glioma patients. Additionally, we suggested that pyroptosis may promote gliomas development by inducing chronic inflammation microenvironment.

Alternative polyadenylation associated with prognosis and therapy in colorectal cancer

Colorectal cancer (CRC) is among the most widely spread cancers globally. Aberrant alternative polyadenylation (APA) plays a role in cancer onset and its progression. Consequently, this study focused on highlighting the role of APA events and signals in the prognosis of patients with CRC. The APA events, RNA sequencing (RNA-seq), somatic mutations, copy number variants (CNVs), and clinical information of the CRC cohort were obtained from The Cancer Genome Atlas (TCGA) database and UCSC (University of California-Santa Cruz) Xena database. The whole set was sorted into two sets: a training set and a test set in a ratio of 7:3. 197 prognosis-related APA events were collected by performing univariate Cox regression signature in patients with CRC. Subsequently, a signature for APA events was established by least absolute shrinkage and selection operator (LASSO) and multivariate Cox analysis. The risk scores were measured for individual patients on the basis of the signature and patients were sorted into two groups; the high-risk group and the low-risk group as per their median risk scores. Kaplan–Meier curves, principal component analysis (PCA), and time-dependent receiver operator characteristic (ROC) curves revealed that the signature was able to predict patient prognosis effectively and further validation was provided in the test set and the whole set. The high-risk and low-risk groups displayed various distributions of mutations and CNVs. Tumor mutation burden (TMB) alone and in combination with the signature predicted the prognosis of CRC patients, but the gene frequencies of TMBs and CNVs did not change in the low- and high-risk groups. Moreover, immunotherapy and chemotherapy treatments showed different responses to PD-1 inhibitors and multiple chemotherapeutic agents in the low and high-risk groups based on the tumor immune dysfunction and exclusion (TIDE) and genomics of drugs sensitivity in cancer (GDSC) databases. This study may help in understanding the potential roles of APA in CRC, and the signature for prognosis-related APA events can work as a potential predictor for survival and treatment in patients with CRC.

Dynamic Deep Genomics Sequence Encoder for Managed File Transfer

The standard communication protocols transfer big data over the internet. However, the challenge lies while sharing the massive amount of genomics data quickly over limited bandwidth networks. Managed File Transfer (MFT) that uses File Transfer Protocol Secure (FTPS) or Secure Shell File Transfer Protocol (SFTP) is a scalable and secure alternative for the purpose. This paper proposes a framework consisting of a Variable-length Genomic Binary Encoding (VGBE) scheme and a hybrid Gated Recurrent Unit-Convolutional Neural Network model (GRU-CNN). The Method exploits Managed File Transfer to reduce the bit size before transmission and increases the bit rate during the transmission of genomics data. Consequently, the method ensures a minimum number of bits per word and less latency. The methodology is tested on various communication protocols. It is validated in terms of performance metrics viz. transfer rate and the size of transferred data using diverse benchmark datasets such as protein sequences and human reference genome taken from the University of California Santa Cruz (UCSC) and National Center for Biotechnology Information (NCBI), respectively. Furthermore, simulation and implementation results show that the model is 98% faster, has 96% less data size, and is more secure than standard communication protocols. Thus, the proposed method is an efficient and secure genomics data transfer method using deep learning techniques.

Wildcat Imaginaries

Abstract The demand for a Cost of Living Adjustment (COLA), made by graduate students at the University of California, Santa Cruz (UCSC), culminated in the wildcat strikes of 2019–20 across the University of California system. Graduate students made a seemingly impossible request of the University of California as it currently operates. The impossibility is not financial: a 60 percent increase in wages, in keeping with the COLA demand, is not unreasonable or impossible but remains the bare minimum to bring graduate students out of an intolerable rent burden. The impossibility of the demand therefore resides in the system's resistance to conceiving of students as “workers.” By insisting on graduate students' status as workers, the COLA struggle implicates the university in the production of low-waged and unwaged academic labor. This struggle demonstrates a commonality between students and a whole class of low-waged and precarious workers at the university that includes university staff, lecturers, and service workers. Extreme precarity that triggered the wildcat strike was intensified by police repression of the picket and the unfolding of the COVID-19 pandemic. As they grapple with the questions of university abolition, the authors of this article examine the structural violences of universities at large, while being attentive to the particularities of the UCSC wildcat strike. The authors draw on the wildcat imaginaries that emerged, in both inchoate and more developed formations, during the strike and offered a glimpse of a possible abolitionist future.

From the Edge through the Vā: Introduction to “Pacific Island Worlds: Oceanic Dis/Positions”

This special issue of Pacific Arts centers on the theme “Pacific Island Worlds: Transpacific Dis/Positions,” which was the topic of a two-day series of events held at the University of California, Santa Cruz (UCSC) in May 2018. This generative meeting explored Oceanic rootedness and mobility, grounded and expansive kinships, worlding, place-making, and colonial histories and their legacies. In important ways, it grew out of the “Native Pacific Cultural Studies on the Edge” symposium, also hosted by UCSC, nearly two decades earlier. “Pacific Island Worlds” was dedicated to the memory of Teresia Teaiwa, a graduate of UCSC’s History of Consciousness doctoral program (2001) who had passed away in 2017 and whose academic, activist, and creative work profoundly inspired Pacific studies scholars and artists around the world. Our introduction is a story of two conferences—moments, pauses, in an ongoing flow of historical, political, and intellectual activity.

Beyond Inclusion: Cultivating a Critical Sense of Belonging through Community-Engaged Research

A broad body of literature outlines the interventions to support underrepresented and minoritized students’ inclusion and sense of belonging into university contexts. In this paper, we explore how two first-generation students of color articulate a critical sense of belonging through their reflections as student researchers in the Apprenticeship in Community-Engaged Research or (H)ACER program at the University of California, Santa Cruz (UCSC). (H)ACER integrates community engagement, ethnographic sensibilities, critical race and decolonial theory, as well as women of color feminisms into a curriculum designed to train critical scholar-researchers. Through themes of feeling isolated on campus and returning ‘home’ in the garden, building comfort with academic theory, and navigating insider/outsider identities in campus/community contexts, we trace how the students developed an awareness of their positionality and made sense of their experiences of ‘belonging’, both within the campus and community contexts. Their narratives spark our deeper exploration into how critical approaches to community-engaged research may offer a pedagogy for supporting student sense of belonging that extends beyond inclusion, a promising vein of further research.

How northern elephant seals mobilise blubber for fuel when fasting

When food is scarce, most animals go into survival mode, reducing their activity to conserve energy. But not northern elephant seals (Mirounga angustirostris). Leaving their ocean feeding grounds and hauling themselves onto Californian and Mexican beaches for weeks, the females give birth, nursing their pups, while the males posture as they protect their harems; all of which they do while fasting. Jane Khudyakov from the University of the Pacific, USA, explains that during this time the animals depend on their extensive fat reserves for survival. However, it wasn't clear how the animals coordinate their tissue energy use while going without. ‘The cellular mechanisms that regulate these adaptations are still not fully understood’, she says. Teaming up with collaborators Dan Crocker (Sonoma State University, USA) and Dan Costa [University of California, Santa Cruz (UCSC), USA], Khudyakov and Rachel Holser (UCSC) headed down to the elephant seals’ breeding grounds at Año Nuevo State Reserve, USA, when the animals returned to moult, to find out.‘They shed old skin and hair within several weeks’, says Khudyakov, adding, ‘it literally peels off in sheets, which makes the beach very smelly’. However, the moulting females are easier to approach than when fasting in the breeding season while protecting their pups. Surrounded by the colony, Holser with colleagues from Costa's lab gently anaesthetised five animals that had just returned from 3–4 month foraging trips, ready for Khudyakov to take small blood, muscle and fat samples at the beginning and end of the moult. In addition, the team weighed the females, recording that the animals lost ∼3 kg per day – totalling ∼28% of their body mass over the ∼33 day period – in the form of skin, hair and fat.Back in the lab, Khudyakov and University of the Pacific undergraduates Serena Ly and Theron Niel extracted proteins from the muscle and blubber before Craig Vierra and Basma Hasan (University of the Pacific) joined them to analyse the protein content, alongside that of the blood sample. ‘We identified 1053 proteins in blubber, 711 in muscle and 260 in blood, most of which have not been studied before in seals’, says Khudyakov. Yet, when the team compared the composition of the muscle and blubber over the month-long fast, they found they had changed little. ‘This suggests that protein turnover in these tissues may be tightly controlled’, says Khudyakov. However, the quantities of three key proteins involved in fat accumulation reduced in all three tissues as the animals switched from storing to consuming fat.In contrast, 53 blood proteins involved in controlling and transporting lipids around the body increased dramatically, including hormones that regulate the release and transport of lipids and those that control how the body uses lipids as a fuel. ‘We think that changes in these proteins may help seals quickly switch their metabolism between feeding and fasting without any of the adverse effects that such rapid fat gain and loss would cause in humans’, says Khudyakov. And when the team checked on the quantities of fat circulating in the animals’ blood, they found that triglycerides – a form of fat – and high-density lipoproteins – ‘good’ cholesterol – did not change significantly, ‘suggesting that seals very tightly regulate their fat reserves, despite using them for energy, during fasting’, says Khudyakov.So, fasting elephant seals are able to sustain an active lifestyle by mobilising fats from their blubber in a controlled way. And Khudyakov is keen to find out how the proteins that regulate fat use change when the females produce full-fat (60%) milk for their pups, although that will require running the gauntlet of the fiercely protective mothers’ teeth.

Chemokine (C-X-C motif) ligand 1/chemokine (C-X-C motif) receptor 2 autocrine loop contributes to cellular proliferation, migration and apoptosis in cervical cancer

ABSTRACT Cervical cancer is the most common malignant tumor in gynecology with high mortality rate, so novel approaches for cervical cancer treatment are urgently needed. In this study, we analyzed the gene expression data and clinicopathological data of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx) downloaded from University of California Santa Cruz (UCSC) Xena database. Chemokine (C-X-C motif) ligand 1 (CXCL1) was screened out as a key prognostic gene for cervical cancer. Revealed by the results of ELISA and Western blot, the expression of CXCL1 and chemokine (C-X-C motif) receptor 2 (CXCR2) in cervical cancer cell lines (HeLa and C33A) was significantly higher than that in the primary cervical epithelial cells. Cellular immunofluorescence was used in this study to observe CXCR2 localization. Through CCK8, clone formation assay, wound healing assay and Annexin V/PI staining, it was found that down-regulation of CXCL1 expression or treatment with CXCR2 antagonist (SB 225002) could reduce the cell viability, affect the proliferation, weaken the migration ability, and promote the apoptosis of cervical cancer cells; however, the effect of CXCR2 antagonist was improved after over-expressed CXCL1. CXCL1/CXCR2 chemokine system regulates the proliferation, migration, and apoptosis of cervical cancer cells in the form of an autocrine loop, thus affecting the development of cervical cancer. This study provides a theoretical basis for researching the molecular mechanism of cervical cancer deterioration and development, and brings forward a new idea for the prevention and treatment of cervical cancer.

Secreted phosphoprotein 1 as a potential prognostic and immunotherapy biomarker in multiple human cancers

ABSTRACT Secreted phosphoprotein 1 (SPP1) is involved in immune regulation, cell survival, and tumor progression. Studies have demonstrated that SPP1 plays an important role in certain individual tumors. However, the expression profile and oncogenic features of SPP1 in diverse cancers are remaining unknown. Therefore, we performed a comprehensive analysis using The Cancer Genome Atlas (TCGA) database. Raw data of 33 cancer types were download from the University of California Santa Cruz (UCSC) Xena website. The expression of SPP1 and its relationship with tumor prognosis, immune invasion, tumor microenvironment, and immunotherapy were analyzed using the R language. The function analysis was conducted using Gene Set Enrichment Analysis (GSEA). The oncogenic features of SPP1 was validated by wound-healing assay and EdU staining assay. SPP1 highly expressed in most cancers. The expression of SPP1 was significant related to prognosis, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint genes, suggested that SPP1 plays an essential role in the tumor immune microenvironment and immune cell infiltration. The immune/stromal scores correlated positively with the SPP1 expression, and the relationship was affected by tumor heterogeneity and immunotherapy. In addition, SPP1 could predict the response of tumor immunotherapy. Functional analysis revealed the SPP1-associated terms and pathways. Finally, SPP1 significantly elevated cell proliferation and migration in A549, Huh7, HT-29, A2780 tumor cell lines. In conclusion, this study indicated that SPP1 involved in tumorigenesis, tumor progression, and regulated tumor immune microenvironment, revealing SPP1 might be a potential target for evaluating prognosis and immunotherapy in multiple cancers.

Immune-related DNA methylation signature associated with APLN expression predicts prognostic of hepatocellular carcinoma

This study used transcriptome and epigenetic data to predict the prognosis of immune-related genes (IRGs) Apelin (APLN) in patients with hepatocellular carcinoma (HCC). The TCGA database has gene expression and clinical data for HCC. And DNA methylation 450 k data for HCC was download from the University of California Santa Cruz (UCSC) Xena browser. Performing clinical and prognostic analysis of APLN expression, results show that APLN is highly expressed in tumor samples. And it has an increasing trend with the development of clinical stage and T stage. To explore the prognostic role of APLN, the Immune-related DNA methylation (DNAm) sites associated with APLN analyzed by bioinformatics. Univariate COX screened the methylation sites that are related to both APLN and survival. The risk score related to methylation site signature was determined according to their least absolute shrinkage and selection operator (LASSO) coefficients. Then the patients were divided into high-risk groups and low-risk groups. Significant differences in overall survival (OS) were found in the training cohort. Nomogram shows that APLN or methylation signature can effectively predict the prognosis of HCC patients. In summary, APLN may be a diagnostic and prognostic marker for HCC.

Construction and analysis of a novel ferroptosis-related gene signature predicting prognosis in lung adenocarcinoma.

Ferroptosis is a newly discovered, iron‐dependent, nonapoptotic form of programmed cell death that plays an important role in the development of lung adenocarcinoma (LUAD). In this study, ferroptosis‐related genes (FRGs) were identified from the FerrDb dataset, and the mRNA expression profiles and corresponding clinical data of LUAD patients were downloaded from the University of California, Santa Cruz (UCSC) databases. Data from LUAD patients from the Gene Expression Omnibus (GEO) dataset were used as the verification set. Cox and Lasso regression analyses were used to screen the FRGs with prognostic value, and six prognostic‐related FRGs were selected to construct prognostic risk score signatures. Immunohistochemistry was utilized to manifest the differential expression of six FRGs in tumor and normal tissues at the protein level. Functional enrichment analysis indicated that FRGs were mainly enriched in ferroptosis‐related pathways. Patients were divided into high‐ and low‐risk groups based on the median risk score. The Kaplan–Meier survival curves confirmed that patients with a high score had significantly worse overall survival. Receiver operating characteristic (ROC) curves proved that the prognostic signature has good sensitivity and specificity for predicting the prognosis of LUAD patients. Nomogram analysis showed that the prognostic signature has potential independent prognostic value. Moreover, the prognostic signature has been shown to be significantly associated with some clinical features (T stage, N stage, tumor stage, and survival status) as well as many immune‐activity‐related genes and immune‐checkpoint‐related genes. In conclusion, we constructed a prognostic signature consisting of six FGRs, which can provide a reference for predicting the prognosis of LUAD patients.

The therapeutic effect of Huazhuojiedu decoction on precancerous lesions in a gastric cancer model via the regulation of lnc 517368

Ethnopharmacological relevanceHuazhuojiedu decoction, a Chinese herbal preparation, has been proven to be clinically effective in treating precancerous lesions in gastric cancer (PLGC). This formula is optimized from a classic formula called “Ganluxiaodu Dan.” Although some experiments have shown that Huazhuojiedu decoction is effective against PLGC, the mechanism remains unclear. Aim of the studyTo investigate the treatment of PLGC with Huazhuojiedu decoction from the perspective of lncRNA in vitro and in vivo. Materials and methodsA PLGC rat model was prepared and randomly divided into a Huazhuojiedu decoction group (HG), a vitacoenzyme group (VG), a model group (MG), and a normal group (CG). Each group was given a corresponding concentration of medicine and distilled water for 10 weeks. The pathological changes in the gastric mucosa were observed by hematoxylin-eosin staining (HE). High-throughput sequencing was performed to detect the differentially expressed lncRNAs in the HG, MG, and CG. Quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) was used to verify differentially expressed lncRNAs, and rat–human homology information was obtained from the University of California, Santa Cruz (UCSC) Genome Database. Human gastric mucosal epithelial cells (GES-1) were used to prepare precancerous lesions of gastric cancer cells (MC). A Huazhuojiedu decoction drug-containing serum was prepared to treat the MC cells. The effects of the Huazhuojiedu decoction and the lncRNA ENST00000517368 (lnc 517368) knockdown or overexpression on PLGC cell proliferation and apoptosis were evaluated in vitro using CCK-8, flow cytometry, and RT-qPCR. ResultsThe HE results showed that gastric mucosal pathology was significantly improved in the HG. High-throughput sequencing results showed that compared with the CG, 91 lncRNAs upregulated in the MG were restored and downregulated in the HG (P < 0.05), and 115 lncRNAs downregulated in the MG were restored and upregulated in the HG (P < 0.05). The results of RT-qPCR were consistent with the sequencing results. The differentially expressed genomic rat lncRNA ENSRNOT00000079699 is homologous to human lnc 517368. In cell experiments, high expression of lnc 517368 promoted proliferation and reduced apoptosis in PLGC cells, while the Huazhuojiedu decoction reduced the expression of lnc 517368 and improved cell morphology. ConclusionsHuazhuojiedu decoction inhibited cell proliferation and promoted apoptosis in PLGC cells, and its effect may be partially dependent on the downregulation of lnc 517368.