Alterations and Co-Occurrence of C-MYC, N-MYC, and L-MYC Expression are Related to Clinical Outcomes in Various Cancers.

Background and Objectives: MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results: We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions: Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.

The Orphan GPR50 Receptor Regulates the Aggressiveness of Breast Cancer Stem-like Cells via Targeting the NF-kB Signaling Pathway.

The expression of GPR50 in CSLC and several breast cancer cell lines was assessed by RT-PCR and online platform (UALCAN, GEPIA, and R2 gene analysis). The role of GPR50 in driving CSLC, sphere formation, cell proliferation, and migration was performed using shGPR50 gene knockdown, and the role of GPR50-regulated signaling pathways was examined by Western blotting and Luciferase Assay. Herein, we confirmed that the expression of G protein-coupled receptor 50 (GPR50) in cancer stem-like cells (CSLC) is higher than that in other cancer cells. We examined that the knockdown of GPR50 in CSLC led to decreased cancer properties, such as sphere formation, cell proliferation, migration, and stemness. GPR50 silencing downregulates NF-kB signaling, which is involved in sphere formation and aggressiveness of CSLC. In addition, we demonstrated that GPR50 also regulates ADAM-17 activity by activating NOTCH signaling pathways through the AKT/SP1 axis in CSLC. Overall, we demonstrated a novel GPR50-mediated regulation of the NF-κB-Notch signaling pathway, which can provide insights into CSLC progression and prognosis, and NF-κB-NOTCH-based CSLC treatment strategies.

Systematic Multiomic Analysis of PKHD1L1 Gene Expression and Its Role as a Predicting Biomarker for Immune Cell Infiltration in Skin Cutaneous Melanoma and Lung Adenocarcinoma.

The identification of genetic factors that regulate the cancer immune microenvironment is important for understanding the mechanism of tumor progression and establishing an effective treatment strategy. Polycystic kidney and hepatic disease 1-like protein 1 (PKHD1L1) is a large transmembrane protein that is highly expressed in immune cells; however, its association with tumor progression remains unclear. Here, we systematically analyzed the clinical relevance of PKHD1L1 in the tumor microenvironment in multiple cancer types using various bioinformatic tools. We found that the PKHD1L1 mRNA expression levels were significantly lower in skin cutaneous melanoma (SKCM) and lung adenocarcinoma (LUAD) than in normal tissues. The decreased expression of PKHD1L1 was significantly associated with unfavorable overall survival (OS) in SKCM and LUAD. Additionally, PKHD1L1 expression was positively correlated with the levels of infiltrating B cells, cluster of differentiation (CD)-8+ T cells, and natural killer (NK) cells, suggesting that the infiltration of immune cells could be associated with a good prognosis due to increased PKHD1L1 expression. Gene ontology (GO) analysis also revealed the relationship between PKHD1L1-co-altered genes and the activation of lymphocytes, including B and T cells. Collectively, this study shows that PKHD1L1 expression is positively correlated with a good prognosis via the induction of immune infiltration, suggesting that PKHD1L1 has potential prognostic value in SKCM and LUAD.

Modulation of Osteogenic Differentiation of Adipose-Derived Stromal Cells by Co-Treatment with 3, 4'-Dihydroxyflavone, U0126, and N-Acetyl Cysteine.

Background and Objectives: Flavonoids form the largest group of plant phenols and have various biological and pharmacological activities. In this study, we investigated the effect of a flavonoid, 3, 4'-dihydroxyflavone (3, 4'-DHF) on osteogenic differentiation of equine adipose-derived stromal cells (eADSCs). Methods and Results: Treatment of 3, 4'-DHF led to increased osteogenic differentiation of eADSCs by increasing phosphorylation of ERK and modulating Reactive Oxygen Species (ROS) generation. Although PD98059, an ERK inhibitor, suppressed osteogenic differentiation, another ERK inhibitor, U0126, apparently increased osteogenic differentiation of the 3, 4'-DHF-treated eADSCs, which may indicate that the effect of U0126 on bone morphogenetic protein signaling is involved in the regulation of 3, 4'-DHF in osteogenic differentiation of eADSCs. We revealed that 3, 4'-DHF could induce osteogenic differentiation of eADSCs by suppressing ROS generation and co-treatment of 3, 4'-DHF, U0126, and/or N-acetyl cysteine (NAC) resulted in the additive enhancement of osteogenic differentiation of eADSCs. Conclusions: Our results showed that co-treatment of 3, 4'-DHF, U0126, and/or NAC cumulatively regulated osteogenesis in eADSCs, suggesting that 3, 4'-DHF, a flavonoid, can provide a novel approach to the treatment of osteoporosis and can provide potential therapeutic applications in therapeutics and regenerative medicine for human and companion animals.

Association of Elevated Expression Levels of COL4A1 in Stromal Cells with an Immunosuppressive Tumor Microenvironment in Low-Grade Glioma, Pancreatic Adenocarcinoma, Skin Cutaneous Melanoma, and Stomach Adenocarcinoma.

Aberrant expression of collagen type IV alpha chain 1 (COL4A1) can influence tumor cell behavior. To examine the association of COL4A1 expression in the tumor microenvironment (TME) with tumor progression, we performed bioinformatics analyses of The Cancer Genome Atlas RNA sequencing and RNA microarray datasets available in public databases and identified upregulated COL4A1 expression in most examined tumor types compared to their normal counterparts. The elevated expression of COL4A1 was correlated with low survival rates of patients with low-grade glioma, pancreatic adenocarcinoma, skin cutaneous melanoma, and stomach adenocarcinoma, thus suggesting its potential use as a biomarker for the poor prognosis of these tumors. However, COL4A1 was mostly expressed in adjacent stromal cells, such as cancer-associated fibroblasts (CAFs) and endothelial cells. Additionally, COL4A1 expression was highly correlated with the signatures of CAFs and endothelial cells in all four tumor types. The expression of marker genes for the infiltration of pro-tumoral immune cells, such as Treg, M2, and TAM, and those of immunosuppressive cytokines exhibited very strong positive correlations with COL4A1 expression. Collectively, our data suggest that COL4A1 overexpression in stromal cells may be a potential regulator of tumor-supporting TME composition associated with poor prognosis.

Prognostic role of EGR1 in breast cancer: a systematic review.

EGR1 (early growth response 1) is dysregulated in many cancers and exhibits both tumor suppressor and promoter activities, making it an appealing target for cancer therapy. Here, we used a systematic multi-omics analysis to review the expression of EGR1 and its role in regulating clinical outcomes in breast cancer (BC). EGR1 expression, its promoter methylation, and protein expression pattern were assessed using various publicly available tools. COSMIC-based somatic mutations and cBioPortal-based copy number alterations were analyzed, and the prognostic roles of EGR1 in BC were determined using Prognoscan and Kaplan-Meier Plotter. We also used bc-GenEx- Miner to investigate the EGR1 co-expression profile. EGR1 was more often downregulated in BC tissues than in normal breast tissue, and its knockdown was positively correlated with poor survival. Low EGR1 expression levels were also associated with increased risk of ER+, PR+, and HER2- BCs. High positive correlations were observed among EGR1, DUSP1, FOS, FOSB, CYR61, and JUN mRNA expression in BC tissue. This systematic review suggested that EGR1 expression may serve as a prognostic marker for BC patients and that clinicopathological parameters influence its prognostic utility. In addition to EGR1, DUSP1, FOS, FOSB, CYR61, and JUN can jointly be considered prognostic indicators for BC. [BMB Reports 2021; 54(10): 497-504].

High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues.

Extracellular vesicles (EVs) are paracrine factors that mediate stem cell therapeutics. We aimed at evaluating the possible therapeutic and esthetic applications of EVs prepared from the waste human facial tissue-derived orbicularis oculi muscle stem cells (OOM-SCs). OOM-SCs were isolated from the ocular tissues (from elders and youngsters) after upper eyelid blepharoplasty or epiblepharon surgeries. EVs were prepared from the OOM-SCs (OOM-SC-EVs) and their three-dimensional spheroids. OOM-SCs showed a spindle-like morphology with trilineage differentiation capacity, positive expression of CD105, CD 90, and CD73, and negative expression of CD45 and CD34, and their stem cell properties were compared with other adult mesenchymal stem cells. OOM-SC-EVs showed a high inhibitory effect on melanin synthesis in B16F10 cells by blocking tyrosinase activity. OOM-SC-EVs treatment led to a significant attenuation of senescence-associated changes, a decrease in reactive oxygen species generation, and an upregulation of antioxidant genes. We demonstrated the regeneration activity of OOM-SC-EVs in in vitro wound healing of normal human dermal fibroblasts and upregulation of anti-wrinkle-related genes and confirmed the therapeutic potential of OOM-SC-EVs in the healing of the in vivo wound model. Our study provides promising therapeutic and esthetic applications of OOM-SC-EVs, which can be obtained from the ocular surgery-derived waste human facial tissues.

Multi-Omics Analysis of SOX4, SOX11, and SOX12 Expression and the Associated Pathways in Human Cancers.

The Sry-related HMG BOX (SOX) gene family encodes transcription factors containing highly conserved high-mobility group domains that bind to the minor groove in DNA. Although some SOX genes are known to be associated with tumorigenesis and cancer progression, their expression and prognostic value have not been systematically studied. We performed multi-omic analysis to investigate the expression of SOX genes in human cancers. Expression and phylogenetic tree analyses of the SOX gene family revealed that the expression of three closely related SOX members, SOX4, SOX11, and SOX12, was increased in multiple cancers. Expression, mutation, and alteration of the three SOX members were evaluated using the Oncomine and cBioPortal databases, and the correlation between these genes and clinical outcomes in various cancers was examined using the Kaplan-Meier, PrognoScan, and R2 database analyses. The genes commonly correlated with the three SOX members were categorized in key pathways related to the cell cycle, mitosis, immune system, and cancer progression in liver cancer and sarcoma. Additionally, functional protein partners with three SOX proteins and their probable signaling pathways were explored using the STRING database. This study suggests the prognostic value of the expression of three SOX genes and their associated pathways in various human cancers.

The Migration of Human Follicular Dendritic Cell-Like Cell Is Facilitated by Matrix Metalloproteinase 3 Expression That Is Mediated through TNFα-ERK1/2-AP1 Signaling.

Follicular dendritic cells are important stromal components of the germinal center (GC) and have pivotal roles in maintaining the GC microenvironment for high-affinity antibody production. Tumor necrosis factor-α (TNFα) is essential for the development and functions of follicular dendritic cells. Despite the importance of follicular dendritic cells in humoral immunity, their molecular control mechanisms have yet to be fully elucidated due to the lack of an adequate investigation system. Here, we have used a unique human primary follicular dendritic cell-like cell (FDCLC) to demonstrate that the migration of these cells is enhanced by TNFα-mediated metalloproteinase 3 (MMP3) expression. MMP3 was found to be highly expressed in normal human GCs and markedly upregulated in human primary FDCLCs by TNFα. TNFα induced ERK1/2 phosphorylation and the transcription of MMP3 through AP1. TNFα treatment increased FDCLC migration, and a knockdown of MMP3 significantly reduced the TNFα-induced migration of FDCLCs. Overall, we have newly identified a control mechanism for the expression of MMP3 in FDCLCs that modulates their migration and may indicate an important role in GC biology. Since GCs are observed in the lesions of autoimmune diseases and lymphomas, targeting the MMP3/TNFα-mediated migration of stromal cells in the B cell follicle may have great potential as a future therapeutic modality against aberrant GC-associated disorders.

Multiomic Analysis of Cereblon Expression and Its Prognostic Value in Kidney Renal Clear Cell Carcinoma, Lung Adenocarcinoma, and Skin Cutaneous Melanoma.

Cereblon (CRBN) is a component of the E3 ubiquitin ligase complex that plays crucial roles in various cellular processes. However, no systematic studies on the expression and functions of CRBN in solid tumors have been conducted to date. Here, we analyzed CRBN expression and its clinical value using several bioinformatic databases. CRBN mRNA expression was downregulated in various cancer types compared to normal cells. Survival analysis demonstrated that overall survival was significantly positively correlated with CRBN expression in some cancer types including lung adenocarcinoma (LUAD), kidney renal clear cell carcinoma (KIRC), and skin cutaneous melanoma (SKCM). CRBN expression was downregulated regardless of clinicopathological characteristics in LUAD and KIRC. Analysis of genes that are commonly correlated with CRBN expression among KIRC, LUAD, and SKCM samples elucidated the potential CRBN-associated mechanisms of cancer progression. Overall, this study revealed the prognostic value of CRBN and its potential associated mechanisms, which may facilitate the development of anti-cancer therapeutic agents.

Expression of ATP/GTP Binding Protein 1 Has Prognostic Value for the Clinical Outcomes in Non-Small Cell Lung Carcinoma.

ATP/GTP binding protein 1 (AGTPBP1) encodes a crucial protein, cytosolic carboxypeptidase 1 (CCP1), which plays a role in modulating the polyglutamylation of tubulin and has been studied in degenerative diseases. However, the role of AGTPBP1 in malignancy has not been completely studied yet. In this study, we examined the role of AGTPBP1 in cancer progression, its association with patient survival, and related mechanisms in lung cancer, using the A549 cell line and lung cancer gene expression datasets. AGTPBP1 knockdown increased the proliferation, migration, sphere formation, and drug resistance of A549 cells. Lung cancer datasets revealed significantly lower mRNA and protein expression levels of AGTPBP1 in lung cancer tissues, as compared to those in normal tissues. Importantly, AGTPBP1 expression positively correlated with patient survival. Analysis of co-expressed genes revealed that AGTPBP1 expression positively correlated with immune infiltration in lung cancer. Our results conclusively suggested that AGTPBP1 expression was correlated with cancer progression and immune infiltration in lung cancer.

Sestrin2 Expression Has Regulatory Properties and Prognostic Value in Lung Cancer.

Lung cancer remains the most dangerous type of cancer despite recent progress in therapeutic modalities. Development of prognostic markers and therapeutic targets is necessary to enhance lung cancer patient survival. Sestrin family genes (Sestrin1, Sestrin2, and Sestrin3) are involved in protecting cells from stress. In particular, Sestrin2, which mainly protects cells from oxidative stress and acts as a leucine sensor protein in mammalian target of rapamycin (mTOR) signaling, is thought to affect various cancers in different ways. To investigate the role of Sestrin2 expression in lung cancer cells, we knocked down Sestrin2 in A549, a non-small cell lung cancer cell line; this resulted in reduced cell proliferation, migration, sphere formation, and drug resistance, suggesting that Sestrin2 is closely related to lung cancer progression. We analyzed Sestrin2 expression in human tissue using various bioinformatic databases and confirmed higher expression of Sestrin2 in lung cancer cells than in normal lung cells using Oncomine and the Human Protein Atlas. Moreover, analyses using Prognoscan and KMplotter showed that Sestrin2 expression is negatively correlated with the survival of lung cancer patients in multiple datasets. Co-expressed gene analysis revealed Sestrin2-regulated genes and possible associated pathways. Overall, these data suggest that Sestrin2 expression has prognostic value and that it is a possible therapeutic target in lung cancer.

Neuropilin1 Expression Acts as a Prognostic Marker in Stomach Adenocarcinoma by Predicting the Infiltration of Treg Cells and M2 Macrophages.

Neuropilin1 (NRP1) plays a critical role in tumor progression and immune responses. Although the roles of NRP1 in various tumors have been investigated, the clinical relevance of NRP1 expression in stomach adenocarcinoma (STAD) has not been studied. To investigate the use of NRP1 as a prognostic biomarker of STAD, we analyzed NRP1 mRNA expression and its correlation with patient survival and immune cell infiltration using various databases. NRP1 mRNA expression was significantly higher in STAD than normal tissues, and Kaplan-Meier survival analysis showed that NRP1 expression was significantly associated with poor prognosis in patients with STAD. To elucidate the related mechanism, we analyzed the correlation between NRP1 expression and immune cell infiltration level. In particular, the infiltration of immune-suppressive cells, such as regulatory T (Treg) cells and M2 macrophage, was significantly increased by NRP1 expression. In addition, the expression of interleukin (IL)-35, IL-10, and TGF-ß1 was also positively correlated with NRP1 expression, resulting in the immune suppression. Collectively in this study, our integrated analysis using various clinical databases shows that the significant correlation between NRP1 expression and the infiltration of Treg cells and M2 macrophage explains poor prognosis mechanism in STAD, suggesting the clinical relevance of NRP1 expression as a prognostic biomarker for STAD patients.

GPR50 Promotes Hepatocellular Carcinoma Progression via the Notch Signaling Pathway through Direct Interaction with ADAM17.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and it is thus critical to identify novel molecular biomarkers of HCC prognosis and elucidate the molecular mechanisms underlying HCC progression. Here, we show that G-protein-coupled receptor 50 (GPR50) in HCC is overexpressed and that GPR50 knockdown may downregulate cancer cell progression through attenuation of the Notch signaling pathway. GPR50 knockdown was found to reduce HCC progression by inactivating Notch signaling in a ligand-independent manner through a disintegrin and metalloproteinase metallopeptidase domain 17 (ADAM17), a proteolytic enzyme that cleaves the Notch receptor, which was corroborated by GPR50 overexpression in hepatocytes. GPR50 silencing also downregulated transcription and translation of ADAM17 through the AKT/specificity protein-1 (SP1) signaling axis. Notably, GPR50 was found to directly interact with ADAM17. Overall, we demonstrate a novel GPR50-mediated regulation of the ADAM17-Notch signaling pathway, which can provide insights into HCC progression and prognosis and development of Notch-based HCC treatment strategies.

Systematic Multiomic Analysis of Ly75 Gene Expression and Its Prognostic Value Through the Infiltration of Natural Killer (NK) Cells in Skin Cutaneous Melanoma.

Ly75 (also known as DEC-205 or CD205) is expressed in immune cells and cancers and involved in tumor immunity. However, clinical relevance of Ly75 expression in skin cutaneous melanoma (SKCM) have not been comprehensively studied. This study analyzed the correlation between Ly75 mRNA expression and patient survival using systematic multiomic analysis tools. Ly75 mRNA expression level was significantly lower in SKCM tissues than in normal tissues. Survival analysis showed that Ly75 expression significantly correlated with good patient survival. To determine possible mechanisms, the association between Ly75 expression and immune cell infiltration was analyzed. Ly75 expression was positively correlated with various infiltrated immune cells, particularly with natural killer (NK) cell infiltration and activation in SKCM. Moreover, analysis of Ly75-co-altered gene expression revealed that Ptprc (CD45) was most significantly correlated with Ly75. Gene ontology analysis of Ly75-co-altered genes indicated the relation to lymphocyte activation, including NK cell activation. Overall, our study provides the first clinical evidence that Ly75 expression is significantly associated with melanoma patient survival and NK cell infiltration, suggesting that Ly75 could be a useful prognostic factor.

Improved Isolation and Culture of Urine-Derived Stem Cells (USCs) and Enhanced Production of Immune Cells from the USC-Derived Induced Pluripotent Stem Cells.

The availability of autologous adult stem cells is one of the essential prerequisites for human stem cell therapy. Urine-derived stem cells (USCs) are considered as desirable cell sources for cell therapy because donor-specific USCs are easily and non-invasively obtained from urine. Efficient isolation, expansion, and differentiation methods of USCs are necessary to increase their availability. Here, we developed a method for efficient isolation and expansion of USCs using Matrigel, and the rho-associated protein kinase (ROCK) inhibitor, Y-27632. The prepared USCs showed significantly enhanced migration, colony forming capacity, and differentiation into osteogenic or chondrogenic lineage. The USCs were successfully reprogramed into induced pluripotent stem cells (USC-iPSCs) and further differentiated into kidney organoid and hematopoietic progenitor cells (HPCs). Using flavonoid molecules, the isolation efficiency of USCs and the production of HPCs from the USC-iPSCs was increased. Taken together, we present an improved isolation method of USCs utilizing Matrigel, a ROCK inhibitor and flavonoids, and enhanced differentiation of USC-iPSC to HPC by flavonoids. These novel findings could significantly enhance the use of USCs and USC-iPSCs for stem cell research and further application in regenerative stem cell-based therapies.

3,2'-Dihydroxyflavone Improves the Proliferation and Survival of Human Pluripotent Stem Cells and Their Differentiation into Hematopoietic Progenitor Cells.

Efficient maintenance of the undifferentiated status of human pluripotent stem cells (hiPSCs) is crucial for producing cells with improved proliferation, survival and differentiation, which can be successfully used for stem cell research and therapy. Here, we generated iPSCs from healthy donor peripheral blood mononuclear cells (PBMCs) and analyzed the proliferation and differentiation capacities of the generated iPSCs using single cell NGS-based 24-chromosome aneuploidy screening and RNA sequencing. In addition, we screened various natural compounds for molecules that could enhance the proliferation and differentiation potential of hiPSCs. Among the tested compounds, 3,2'-dihydroxyflavone (3,2'-DHF) significantly increased cell proliferation and expression of naïve stemness markers and decreased the dissociation-induced apoptosis of hiPSCs. Of note, 3,2'-DHF-treated hiPSCs showed upregulation of intracellular glutathione (GSH) and an increase in the percentage of GSH-high cells in an analysis with a FreSHtracer system. Interestingly, culture of the 3,2'-DHF-treated hiPSCs in differentiation media enhanced their mesodermal differentiation and differentiation into CD34+ CD45+ hematopoietic progenitor cells (HPC) and natural killer cells (NK) cells. Taken together, our results demonstrate that the natural compound 3,2'-DHF can improve the proliferation and differentiation capacities of hiPSCs and increase the efficiency of HPC and NK cell production from hiPSCs.

Interleukin-18 Is a Prognostic Biomarker Correlated with CD8+ T Cell and Natural Killer Cell Infiltration in Skin Cutaneous Melanoma.

Interleukin-18 (IL-18) is a cytokine that enhances innate and adaptive immune responses. Although there are conflicting reports about the roles of IL-18 in melanoma progression, the clinical relevance of IL-18 expression has not been comprehensively studied. In this study, we investigated IL-18 expression and its correlation with patient survival and immune cell infiltration in melanoma using cancer gene expression data publicly available through various databases. IL18 mRNA expression was found to be significantly lower in melanoma tissues than normal tissues. Kaplan-Meier survival analysis showed that IL18 expression was positively correlated with patient survival. To investigate the possible mechanisms by which IL18 expression increased patient survival, we then assessed the correlation between IL18 expression and immune cell infiltration levels. Infiltration of various immune cells, especially CD8+ T and natural killer (NK) cells, which are cytolytic effector cells, was significantly increased by IL18 expression. Additionally, the expression levels of two cytolytic molecules including perforin and granzyme B were significantly positively correlated with IL18 expression. Collectively, this study provides the first evidence that IL18 expression has prognostic value for melanoma patient survival and is strongly correlated with CD8+ T and NK cell infiltration, suggesting the role of IL-18 as a biomarker for predicting melanoma prognosis.

High Expression of TTYH3 is Related to Poor Clinical Outcomes in Human Gastric Cancer.

Ion channels play important roles in regulating various cellular processes and malignant transformation. Expressions of some chloride channels have been suggested to be associated with patient survival in gastric cancer (GC). However, little is known about the expression and function of TTYH3, a gene encoding a chloride ion channel, in cancer progression. Here, we comprehensively analyzed the expression of TTYH3 and its clinical outcome in GC using publicly available cancer gene expression and patient survival data through various databases. We examined the differences of TTYH3 expression between cancers and their normal tissues using the Oncomine, UALCAN, and GEO (Gene Expression Omnibus) databases. TTYH3 expression was investigated from immunohistochemistry images using the Human Protein Atlas database. Copy number alterations and mutations of TTYH3 were analyzed using cBioPortal. The co-expression profile of TTYH3 in GC was revealed using Oncomine. The gene ontology and pathway analyses were done using those co-expressed genes via the Enrichr tool to explore the predicted signaling pathways in GC. TTYH3 mRNA and protein levels in GC were significantly greater than those in normal tissue. Kaplan-Meier analysis revealed the upregulation of TTYH3 expression, which was significantly correlated with worse patient survival. Collectively, our data suggest that TTYH3 might be a potential prognostic marker for GC patients.

Systematic Multiomics Analysis of Alterations in C1QBP mRNA Expression and Relevance for Clinical Outcomes in Cancers.

C1QBP (Complement Component 1 Q Subcomponent-Binding Protein), a multicompartmental protein, participates in various cellular processes, including mRNA splicing, ribosome biogenesis, protein synthesis in mitochondria, apoptosis, transcriptional regulation, and infection processes of viruses. The correlation of C1QBP expression with patient survival and molecular function of C1QBP in relation to cancer progression has not been comprehensively studied. Therefore, we sought to systematically investigate the expression of C1QBP to evaluate the change of C1QBP expression and the relationship with patient survival and affected pathways in breast, lung, colon, and bladder cancers as well as lymphoma. Relative expression levels of C1QBP were analyzed using the Oncomine, Gene Expression Across Normal and Tumor Tissue (GENT), and The Cancer Genome Atlas (TCGA) databases. Mutations and copy number alterations in C1QBP were also analyzed using cBioPortal, and subsequently, the relationship between C1QBP expression and survival probability of cancer patients was explored using the PrognoScan database and the R2: Kaplan Meier Scanner. Additionally, the relative expression of C1QBP in other cancers, and correlation of C1QBP expression with patient survival were investigated. Gene ontology and pathway analysis of commonly differentially coexpressed genes with C1QBP in breast, lung, colon, and bladder cancers as well as lymphoma revealed the C1QBP-correlated pathways in these cancers. This data-driven study demonstrates the correlation of C1QBP expression with patient survival and identifies possible C1QBP-involved pathways, which may serve as targets of a novel therapeutic modality for various human cancers.