ZNF695, A Potential Prognostic Biomarker, Correlates with Immune Infiltrates in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma: Bioinformatic Analysis and Experimental Verification.

BACKGROUND: The role of Zinc Finger Protein 695 (ZNF695) is unclear in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). OBJECTIVE: The objective of this study was to conduct a comprehensive analysis and experimental validation of ZNF695 in CESC. METHODS: The study investigated the expression of ZNF695 in both pan-cancer and CESC, utilizing data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The present study investigated the association between ZNF695 expression levels and clinical characteristics, as well as prognosis, in patients with CESC. The study explored potential regulatory networks involving ZNF695, including its association with immune infiltration, immune score, stemness index based on mRNA expression (mRNAsi), and drug sensitivity in CESC. We explored the expression of ZNF695 in CESC single cells. ZNF695 expression was validated using GSE29570. RESULTS: ZNF695 was found to be aberrantly expressed in pan-cancer and CESC. There was a significant correlation observed between an elevated level of ZNF695 expression in patients with CESC and histological grade (p = 0.017). Furthermore, a strong association was found between high ZNF695 expression in CESC patients and poorer overall survival (OS) (HR: 1.87; 95% CI: 1.17-3.00; p = 0.009), Progression-free Survival (PFS) (HR: 1.86; 95% CI: 1.16-2.98; p = 0.010), and Disease-specific Survival (DSS) (HR: 1.98; 95% CI: 1.15-3.42; p = 0.014). The expression of ZNF695 in CESC patients (p = 0.006) was identified as an independent prognostic determinant. ZNF695 was associated with steroid hormone biosynthesis, oxidative phosphorylation, and so on. ZNF695 expression correlated with immune infiltration, immune score, and mRNAsi in CESC. ZNF695 expression significantly and negatively correlated with AICA ribonucleotide, BIX02189, QL-XI-92, STF-62247, and SNX-2112 in CESC. ZNF695 gene was upregulated in CESC tissues and cell lines. ZNF695 was significantly upregulated in the CESC cell lines. CONCLUSION: ZNF695 may be a potential prognostic biomarker and immunotherapeutic target for CESC patients.

TPD52 as a Potential Prognostic Biomarker and its Correlation with Immune Infiltrates in Uterine Corpus Endometrial Carcinoma: Bioinformatic Analysis and Experimental Verification.

BACKGROUND: Aberrant expression of tumor protein D52 (TPD52) is associated with some tumors. The role of TPD52 in uterine corpus endometrial carcinoma (UCEC) remains uncertain. OBJECTIVE: We aimed to investigate the involvement of TPD52 in the pathogenesis of UCEC. METHODS: We employed bioinformatics analysis and experimental validation in our study. RESULTS: Our findings indicated that elevated TPD52 expression in UCEC was significantly associated with various clinical factors, including clinical stage, race, weight, body mass index (BMI), histological type, histological grade, surgical approach, and age (p < 0.01). Furthermore, high TPD52 expression was a predictor of poorer overall survival (OS), progress-free survival (PFS), and disease-specific survival (DSS) (p = 0.011, p = 0.006, and p = 0.003, respectively). TPD52 exhibited a significant correlation with DSS (HR: 2.500; 95% CI: 1.153-5.419; p = 0.02). TPD52 was involved in GPCR ligand binding and formation of the cornified envelope in UCEC. Moreover, TPD52 expression was found to be associated with immune infiltration, immune checkpoints, tumor mutation burden (TMB)/ microsatellite instability (MSI), and mRNA stemness indices (mRNAsi). The somatic mutation rate of TPD52 in UCEC was 1.9%. A ceRNA network of AC011447.7/miR-1-3p/TPD52 was constructed. There was excessive TPD52 protein expression. The upregulation of TPD52 expression in UCEC cell lines was found to be statistically significant. CONCLUSION: TPD52 is upregulated in UCEC and may be a useful patent for prognostic biomarkers of UCEC, which may have important value for clinical treatment and supervision of UCEC patients.

NOTCH Pathway Genes in Ovarian Cancer: Clinical Significance and Associations with Immune Cell Infiltration.

BACKGROUND: Activation of the NOTCH signaling pathway is associated with tumorigenesis. The aim of this study was to investigate NOTCH pathway gene functions and regulatory mechanisms in ovarian cancer (OC). METHODS: We conducted a bioinformatics analysis of publicly available datasets in order to identify potential NOTCH-related mechanisms, associated genes, biological pathways, and their relation to immune function. RESULTS: Significant differential expression of the NOTCH pathway genes DLL1, DLL3, DLL4, HES1, HEY1, JAG1, NOTCH2, NOTCH3, and NOTCH4 was observed between OC samples and normal controls. Low expression of DLL4 and of NOTCH4 in OC patients was associated with International Federation of Gynecology and Obstetrics (FIGO) stage (p <0.001 and p = 0.036, respectively), while high expression of NOTCH3 was associated with race (p = 0.039) and age (p = 0.044). JAG2 and NOTCH1 expression were significantly associated with progression-free interval (PFI) (p = 0.011 and p = 0.039, respectively). DLL1 (Hazard Ratio (HR): 2.096; 95% CI: 1.522-2.886, p < 0.001) and NOTCH1 (HR: 0.711; 95% CI: 0.514-0.983, p = 0.039) expression were independently associated with PFI in multivariate analysis. DLL1, DLL3, JAG1, JAG2, NOTCH3 and NOTCH4 expression could significantly differentiate OC from non-cancer samples. Genes associated with the NOTCH pathway were mainly enriched in five signaling pathways: the NOTCH signaling pathway, breast cancer, endocrine resistance, Th1 and Th2 cell differentiation, and oxidative phosphorylation. The expression of NOTCH pathway genes was significantly associated with immune cell infiltration. CONCLUSIONS: NOTCH pathway genes appear to play an important role in the progression of OC by regulating immune cells, endocrine resistance, Th1 and Th2 cell differentiation, and oxidative phosphorylation. JAG2 and NOTCH1 are potential biomarkers and therapeutic targets for the treatment of OC.

Comprehensive analysis of TLX2 in pan cancer as a prognostic and immunologic biomarker and validation in ovarian cancer.

T cell leukemia homeobox 2 (TLX2) plays an important role in some tumors. Bioinformatics and experimental validation represent a useful way to explore the mechanisms and functions of TLX2 gene in the cancer disease process from a pan cancer perspective. TLX2 was aberrantly expressed in pan cancer and cell lines and correlated with clinical stage. High TLX2 expression was significantly associated with poor overall survival in COAD, KIRC, OC, and UCS. The greatest frequency of TLX2 alterations in pan cancer was amplification. Alterations of NXF2B, MSLNL, PCGF1, INO80B-WBP1, LBX2-AS1, MRPL53, LBX2, TTC31, WDR54, and WBP1 co-occurred in the TLX2 alteration group. PFS was significantly shorter in the TLX2-altered group (n = 6) compared to the TLX2-unaltered group (n = 400). Methylation levels of TLX2 were high in 17 tumors. TLX2 expression was associated with MSI in seven tumors and TMB in five tumors. TLX2 expression was associated with immune infiltration and immune checkpoint genes. TLX2 may be associated with some pathways and chemoresistance. We constructed a possible competing endogenous RNA (ceRNA) network of LINC01010/miR-146a-5p/TLX2 in OC. TLX2 expression was significantly upregulated in ovarian cancer cell lines compared to ovarian epithelial cell lines. Aberrant expression of TLX2 in pan cancer may promote tumorigenesis and progression through different mechanisms. TLX2 may represent an important therapeutic target for human cancers.

PAXIP1-AS1 is associated with immune infiltration and predicts poor prognosis in ovarian cancer.

The long non-coding RNA (LncRNA) PAXIP1 antisense RNA 1 (PAXIP1-AS1) was found to promote proliferation, migration, EMT, and apoptosis of ovarian cancer (OC) cells in OC cell lines, but the relationship between PAXIP1-AS1 expression and clinical characteristics, prognosis, and immune infiltration of OC patients and its regulatory network are unclear. 379 OC tissues were collected from The Cancer Genome Atlas (TCGA) database. 427 OC tissues and 88 normal ovarian tissues were collected from GTEx combined TCGA database. 130 OC samples were collected from GSE138866. Kruskal-Wallis test, Wilcoxon sign-rank test, logistic regression, Kaplan-Meier method, Cox regression analysis, Gene set enrichment analysis (GSEA), and immuno-infiltration analysis were used to evaluate the relationship between clinical characteristics and PAXIP1-AS1 expression, prognostic factors, and determine the significant involvement of PAXIP1-AS1 in function. QRT-PCR was used to validate the expression of PAXIP1-AS1 in OC cell lines. Low PAXIP1-AS1 expression in OC was associated with age (P = 0.045), histological grade (P = 0.011), and lymphatic invasion (P = 0.004). Low PAXIP1-AS1 expression predicted a poorer overall survival (OS) (HR: 0.71; 95% CI: 0.55-0.92; P = 0.009), progression free interval (PFS) (HR: 1.776; 95% CI: 1.067-2.955; P = 0.001) and disease specific survival (DSS) (HR: 0.67; 95% CI: 0.51-0.89; P = 0.006). PAXIP1-AS1 expression (HR: 0.711; 95% CI: 0.542-0.934; P = 0.014) was independently correlated with PFS in OC patients. GSEA demonstrated that neutrophil degranulation, signaling by Interleukins, GPCR-ligand binding, G alpha I signaling events, VEGFAVEGFR-2 signaling pathway, naba secreted factors, Class A 1 Rhodopsin-Like Receptors, PI3K-Akt signaling pathway, and Focal Adhesion-PI3K-Akt-mTOR-signaling pathway were differentially enriched in PAXIP1-AS1 high expression phenotype. PAXIP1-AS1 was significantly downregulated in OC cell lines compared with IOSE29 cell line. The expression of PAXIP1-AS1 was associated with immune infiltration. low expression of PAXIP1-AS1 was correlated with poor OS (HR: 0.52; 95% CI: 0.34-0.80; P = 0.003) from GSE138866. There were some genomic variations between the PAXIP1-AS1 high and low expression groups. Low expression of PAXIP1-AS1 was significantly associated with poor survival and immune infiltration in OC. PAXIP1-AS1 could be a promising prognosis biomarker and response to immunotherapy for OC.

Experimental Research on a New Mini-Channel Transcritical CO2 Heat Pump Gas Cooler.

This paper presents the results of an experimental study on the heat transfer and pressure drop characteristics of a novel spiral plate mini-channel gas cooler designed for use with supercritical CO2. The CO2 channel of the mini-channel spiral plate gas cooler has a circular spiral cross-section with a radius of 1 mm, while the water channel has an elliptical cross-section spiral channel with a long axis of 2.5 mm and a short axis of 1.3 mm. The results show that increasing the mass flux of CO2 can effectively enhance the overall heat transfer coefficient when the water side mass flow rate is 0.175 kg·s-1 and the CO2 side pressure is 7.9 MPa. Increasing the inlet water temperature can also improve the overall heat transfer coefficient. The overall heat transfer coefficient is higher when the gas cooler is vertically oriented compared to horizontally oriented. A Matlab program was developed to verify that the correlation based on Zhang's method has the highest accuracy. The study found a suitable heat transfer correlation for the new spiral plate mini-channel gas cooler through experimental research, which can provide a reference for future designs.

TPD52 is a Potential Prognostic Biomarker and Correlated with Immune Infiltration: A Pan-cancer Analysis.

BACKGROUND: Some tumors have a poor prognosis regarding TPD52 (tumor protein D52). This study aims to explore TPD52's role in the cancer process from a pan-cancer perspective. METHODS: A pan-cancer analysis was conducted to investigate how TPD52 may be involved in cancer as well as its association with prognosis. RESULTS: A variety of human cancers express TPD52 abnormally and correlate with clinical stage. There was a significant association between low expression of TPD52 and poor survival in BRCA, KIRP, LAML, LIHC, UCEC, and UVM. TPD52 alterations were most frequently amplified in pan-cancer. The co-occurrence of 10 genes alterations was found in the TPD52 altered group. There was a significant association between TPD52 expression and MSI in four cancer types and TMB in twelve cancer types. There was a significant correlation between TPD52 expression and immunerelated cell infiltration. A significant correlation was found between TPD52 expression in many tumor types and 8 immune checkpoint genes. There were signaling pathways involved in pan-cancer caused by TPD52, including endocytosis, Fc gamma Rmediated phagocytosis, and so on. TPD52 may be involved in chemotherapy and chemoresistance. CONCLUSION: The TPD52 gene may be important for human cancer treatment.

Molecular Analysis of Prognosis and Immune Infiltration of Ovarian Cancer Based on Homeobox D Genes.

Background: Homeobox D (HOXD) genes were associated with cancer pathogenesis. However, the role of HOXD genes in ovarian cancer (OC) and the possible mechanisms involved are unclear. In this study, we analyzed the function and regulatory mechanisms and functions of HOXD genes in OC based on comprehensive bioinformatics analysis. Methods: Expression of HOXD1/3/4/8/9/10/11/12/13 mRNA was analyzed between OC tissue and normal tissue using ONCOMINE, GEO, and TCGA databases. The relationship between HOXD expression and clinical stage was studied by GEPIA. The Kaplan-Meier plotter was used to analyze prognosis. cBioPortal was used to analyze the mutation and coexpression of HOXDs. GO and KEGG analyses were performed by the DAVID software to predict the function of HOXD coexpression genes. Immune infiltration analysis was used to evaluate the relationship between the expression of HOXD genes and 24 immune infiltrating cells. Results: The expression of HOXD3/4/8/9/10/11 was significantly lower in OC tissues than in normal ovarian tissues, while the expression of HOXD1/12/13 was significantly higher in OC tissues. The expression of HOXD genes was associated with FIGO stage, primary therapy outcome, tumor status, anatomic neoplasm subdivision, and age. The expression levels of HOXD1/3/4/8/9/10 correlated with tumor stage. HOXD1/8/9 could be served as ideal biomarkers to distinguish OC from normal tissue. Low HOXD9 expression was associated with shorter overall survival (OS) (HR: 0.75; 95% CI: 0.58-0.98; P = 0.034) and progression-free survival (PFS) (HR: 0.69; 95% CI: 0.54-0.87; P = 0.002). The HOXD coexpression genes were associated with pathways including cell cycle, TGF-beta signaling pathway, cellular senescence, and Hippo signaling pathway. HOXD genes were significantly associated with immune infiltration. Conclusion: The expression of HOXD genes is associated with clinical characteristics. HOXD9 is a new biomarker of prognosis in OC, and HOXD1/4/8/9/10 may be potential therapeutic targets. The members of the HOXD genes may be the response to immunotherapy for OC.

Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway.

Ovarian cancer is one of the most common gynecological malignancies in women worldwide with a poor survival rate. Cinnamaldehyde (CA), a bioactive substance isolated from cinnamon bark, is a natural drug and has shown that it can inhibit the progression of other tumors. However, the role of CA in ovarian cancer and its mechanism is poorly understood. In this study, wound healing assays, plate cloning, CCK-8, and transwell assays were used to determine cell proliferation and invasion. Western blot and flow cytometry were used to detect apoptosis levels. Western blot and immunofluorescence were used to detect changes in cellular EMT levels. The Western blot was used to detect levels of the PI3K/AKT signaling pathway. In vivo, we established a subcutaneous transplantation tumor model in nude mice to verify the role of CA in the progression and metastasis of ovarian cancer. Our data showed that in vitro CA was able to inhibit the cell viability of ovarian cancer. The results of scratch assay and transwell assay also showed that CA inhibited the proliferation and invasion ability of A2780 and SKOV3 cells. In addition, CA promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase 3 in ovarian cancer cells. Mechanistically, we found that CA inhibited the EGF-induced PI3K/AKT signaling pathway and reduced the phosphorylation levels of mTOR, PI3K, and AKT. The EGF-induced EMT process was also abolished by CA. The EMT process induced by AKT-specific activator SC79 was also suppressed by CA. Furthermore, in in vivo, CA significantly repressed the progression of ovarian cancer as well as liver metastasis. In all, our results suggest that CA inhibits ovarian cancer progression and metastasis in vivo and in vitro and inhibits EGF-induced EMT processes through the PI3K/AKT signaling pathway.

miR-149-3p Is a Potential Prognosis Biomarker and Correlated with Immune Infiltrates in Uterine Corpus Endometrial Carcinoma.

Background: Endocrine disruption is an important factor in the development of endometrial cancer. Expression of miR-149-3p is observed in some cancer types, while its role in uterine corpus endometrial carcinoma (UCEC) is unclear. Methods: The clinical and genomic data and prognostic information on UCEC were obtained for patients from the TCGA database. The Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to analyze the relationship between clinical characteristics and miR-149-3p expression. Kaplan-Meier survival curve analysis was used to study the influence of miR-149-3p expression and miR-149-3p target genes on the prognosis of UCEC patients. The TargetScan, PicTar, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine the involvement of miR-149-3p target genes in function. Immune infiltration analysis was used to analyze the functional involvement of miR-149-3p. QRT-PCR was used to validate the expression of miR-149-3p in UCEC cell lines. Results: High expression of miR-149-3p in UCEC was significantly associated with age (P < 0.001), histological type (P < 0.001), histological grade (P < 0.001), tumor invasion (P=0.014), and radiation therapy (P=0.011). High miR-149-3p expression predicted poorer overall survival (OS) (HR: 2.56; 95% CI: 1.64-4.00; P < 0.001), progression-free interval (PFI) (HR: 1.85; 95% CI: 1.29-2.65; P=0.001), and disease-specific survival (DSS) (HR: 2.33; 95% CI: 1.37-3.99; P=0.002). Low expressions of miR-149-3p target genes, including ADCYAP1R1, CGNL1, CHST3, CYGB, DNAH9, ESR1, HHIP, HIC1, HOXD11, IGF1, INMT, LSP1, MTMR10, NFIC, PLCE1, RARA, SNTN, SPRYD3, and ZBTB7A, were associated with poor OS in UCEC. MiR-149-3p may be involved in the occurrence and development of UCEC via pathways including PI3K-Akt signaling pathway, Ras signaling pathway, AGE-RAGE signaling pathway in diabetic complications, focal adhesion, and MAPK signaling pathway. miR-149-3p may inhibit the function of CD8 T cells, cytotoxic cells, eosinophils, iDC, mast cells, neutrophils, NK CD56bright cells, NK CD56dim cells, pDC, T cells, T helper cells, TFH, Th17 cells, and Treg. miR-149-3p was significantly upregulated in UCEC cell lines compared with endometriotic stromal cells. Conclusion: High expression of miR-149-3p was significantly associated with poor survival in UCEC patients. It may be a promising biomarker of prognosis and response to immunotherapy for UCEC patients.

Expression, Clinical Significance, and Prospective Pathway Signaling of miR-501-3p in Ovarian Cancer Based on Database and Informatics Analysis.

BACKGROUND: The present study aims to explore the expression, clinical significance, and prospective pathway signaling of miR-501-3p in ovarian cancer (OC) based on database and informatics analysis. METHODS: Kruskal-Wallis test, Wilcoxon sign-rank test, and logistic regression were used to evaluate the relationship between clinical features and miR-501-3p expression. Kaplan-Meier survival curve analysis was used to explore the relationship between miR-501-3p expression and the prognosis of OC patients. The miRNA targets were obtained from databases TargetScan, miRanda, TarBase, miRTarBase, miR2Disease, miRecords, and miRWalk. GO and KEGG analyses were used to analyze the significant involvement of miR-501-3p target genes in function. RESULTS: The low miR-501-3p expression in OC was significantly associated with histologic grade (P=0.015). Low miR-501-3p expression predicted a poorer overall survival (HR: 0.77; 95% CI: 0.61-0.96; P=0.02) and disease-specific survival (HR: 0.77; 95% CI: 0.61-0.99; P=0.038). GO and KEGG analyses demonstrated that miR-501-3p might participate in the development of OC by pathways including one carbon pool by folate, protein digestion and absorption, cell cycle, kaposi sarcoma-associated herpesvirus infection, and viral carcinogenesis. CONCLUSIONS: Low miR-501-3p expression is significantly associated with poor survival in OC patients. It may be a promising prognostic biomarker for OC patients.

The Immune-Related Gene ELF3 is a Novel Biomarker for the Prognosis of Ovarian Cancer.

BACKGROUND: Ovarian cancer (OC) is a fatal gynaecological malignancy. The study aimed to conduct a comprehensive study to determine the role of ELF3 in OC through bioinformatic analysis. METHODS: Kruskal-Wallis test, Wilcoxon sign-rank test, and logistic regression were used to evaluate the relationship between clinical characteristics and ELF3 expression. Kaplan-Meier method and Cox regression analysis were used to evaluate the prognostic factors. Gene set enrichment analysis (GSEA) and immuno-infiltration analysis were used to evaluate the significant involvement of ELF3 in function. RESULTS: High ELF3 expression in OC was associated with age (P< 0.001). High ELF3 expression predicted a poorer overall survival (OS) (HR: 1.37; 95% CI: 1.05-1.78; P=0.019) and disease specific survival (DSS) (HR: 1.43; 95% CI: 1.08-1.89; P=0.013). And ELF3 expression (HR: 1.779; 95% CI: 1.281-2.472; P<0.001) was independently correlated with OS in OC patients. GSEA demonstrated that pathways including GPCR-ligand binding, neuronal system, signaling by WNT, translation, neuroactive ligand-receptor interaction, and TCF dependent signaling in response to WNT were differentially enriched in ELF3 low expression phenotype. Immune infiltration analysis showed that ELF3 expression was correlated with immune infiltrates. CONCLUSION: ELF3 expression in OC patients was significantly associated with poor survival and immune infiltration and a promising prognostic biomarker in OC.

MiR-585-3p suppresses tumor proliferation and migration by directly targeting CAPN9 in high grade serous ovarian cancer.

BACKGROUND: Aberrant expression of microRNAs (miRNAs) contributes to the development of high grade serous ovarian cancer (HGSOC). However, the molecular mechanism by which miRNA-585-3p mediates high-grade serous ovarian carcinogenesis is unclear. This study aims to investigate the specific mechanism of action of miR-585-3p in HGSOC. METHODS: Expression of miR-585-3p in HGSOC tissues and cell lines was detected by qRT-PCR. Cell viability and migration were detected using MTT and transwell system. The expression of target genes and target proteins of miR-585-3p was detected by dual luciferase reporter assay and western blot. RESULTS: The expression of miR-585-3p was significantly lower in HGSOC tissues and cells than in normal ovarian tissues and cell lines. In HGSOC tissues, CAPN9 expression was inversely correlated with miR-585-3p expression. MiR-585-3p inhibited the proliferation and migration of HGSOC cells. MiR-585-3p bound to the 3'-untranslated region (UTR) of CAPN9 and inhibits CAPN9 expression. Overexpression of CAPN9 reduced the inhibitory effect of miR-585-3p in HGSOC cells. CONCLUSIONS: miR-585-3p is significantly down-regulated in HGSOC tissues and cell lines. MiR-585-3p inhibits the proliferation and migration of HGSOC cells by targeting CAPN9.

Bioinformatics Analysis of KIF1A Expression and Gene Regulation Network in Ovarian Carcinoma.

BACKGROUND: The study aims to analyze the expression levels of kinesin family member 1A (KIF1A) in ovarian cancer (OC) and explore its clinical significance in the development of OC and its potential regulatory network. METHODS: The Cancer Genome Atlas (TCGA) OC data was used to examine the expression differences between OC and normal tissue and explore the correlation with tumor stage. The relationship between KIF1A expression and prognosis was analyzed using Oncomine and Kaplan-Meier plotter tools. The co-expression network of KIF1A in TCGA OC was analyzed based on the application of cBioPortal, GO cluster, and KEGG analyses were performed based on the co-expression network. Immune-infiltration analysis were used to analyze the significant involvement of KIF1A in function. RESULTS: KIF1A was highly elevated in OC tissues and KIF1A expression was significantly correlated with the FIGO stage (P=0.015) and age (P=0.020). High KIF1A expression of OC predicted the poor prognosis including overall survival (OS) (HR: 1.27; 95% CI: 1.11-1.45; P=0.00046) and post-progression survival (PFS) (HR: 1.18; 95% CI: 1.03-1.35; P=0.015). GO and KEGG analysis showed KIF1A had a potential role in the biological process of ATP-dependent chromatin remodeling, transcription, DNA-templated cytolysis, positive regulation of T cell proliferation, positive regulation of transcription, DNA-templated via cell adhesion molecules (CAMs), primary immunodeficiency, oxidative phosphorylation, NF-kappa B signaling pathway, pathways in cancer and Wnt signaling pathway, and immune infiltrating cells. CONCLUSION: KIF1A was highly expressed and correlated with poor survival and immune infiltration in OC, and it may be a prognostic biomarker in OC.

Differential Expression Profiles and Function Prediction of Transfer RNA-Derived Fragments in High-Grade Serous Ovarian Cancer.

BACKGROUND: The present study is aimed at providing systematic insight into the composition and expression of transfer RNA (tRNA) derivative transcription in high-grade serous ovarian cancer (HGSOC). METHODS: tRNA derivative expression profiles in three pairs of HGSOC and adjacent normal ovarian tissues were conducted by tRNA-derived small RNA fragment (tRF) and tRNA half (tiRNA) sequencing. The differentially expressed tRFs and tiRNAs between HGSOC and paired adjacent normal samples were screened. The targeted genes of differentially expressed tRFs and tiRNAs were screened. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) of target genes of tRFs and tiRNAs were analyzed. RESULTS: There are a total of 20 significantly upregulated and 15 significantly downregulated tRFs and tiRNAs between the cancer group and the paracarcinoma group. The upregulated tRFs and tiRNAs are mucin-type O-glycan biosynthesis, glycosphingolipid biosynthesis, the glucagon signaling pathway, the AMPK signaling pathway, maturity-onset diabetes of the young, glycosphingolipid biosynthesis, the insulin signaling pathway, insulin resistance, leukocyte transendothelial migration, starch, and sucrose metabolism. The downregulated tRFs and tiRNAs are other glycan degradation, vitamin digestion and absorption, fatty acid elongation, and biosynthesis of unsaturated fatty acids. CONCLUSIONS: There are significantly expressed tRFs and tiRNAs in HGSOC tissues, and these may provide potential diagnostic biomarkers and therapeutic targets for HGSOC.

Expression of PKG2 in ovarian cancer and its effect on epidermal growth factor receptor.

PURPOSE: This research tried to explore the expression level of II cGMP-dependent protein kinase (PKG2) in human ovarian tissue and to clarify the molecular mechanism of EGFR regulation and its clinical significance. METHODS: The expression levels of PKG2 and EGFR in 10 normal ovarian tissues, 14 benign ovarian tumor tissues and 39 epithelial ovarian cancer tissues preserved in the archives of the Affiliated Hospital of Xuzhou Medical University from 2016 to 2018 were detected by real-time fluorescence quantitative (RT-PCR), and the correlation between the expressions of the two genes was analyzed. The expressions of in vitro cultured ovarian cancer cell lines SKOV3, PKG2 and EGFR were detected by RT-PCR and western blot, and the over-expressed PKG2 plasmid and PKG2 small interfering RNA (siRNA) were transfected into the cells, and the protein and phosphorylation of Akt and ERK in EGFR and its downstream signaling pathway were detected by western blot. RESULTS: Compared with normal ovarian tissue, the mRNA and protein expression levels of PKG2 in ovarian cancer tissue and SKOV3 cell line were significantly reduced (p<0.05). However, the mRNA and protein expression levels of EGFR in ovarian cancer tissue and SKOV3 cell line were both high (p<0.05). In addition, after transient transfection of PKG2, the expression changes of PKG2 significantly affected the expression of EGFR, and PKG2 over-expression could significantly inhibit the phosphorylation of Akt and ERK in EGFR and its downstream signaling pathways, thereby affecting cell proliferation. CONCLUSION: PKG2 may play a role in inhibiting EGFR expression in ovarian cancer, but the specific mechanism of its effect on tumor development still needs to be further explored.