scholarly journals Prognostic Value and Immune Infiltration Analysis of Nuclear Factor Erythroid-2 Family Members in Ovarian Cancer

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Rui Dou ◽  
Xiong Wang ◽  
Jin Zhang
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Gynecological Cancer ◽  
Family Members ◽  
Progression Free Survival ◽  
Antioxidant Response ◽  
Genetic Alterations ◽  
Nuclear Factor ◽  
Immune Infiltration ◽  
Bioinformatics Databases

Ovarian cancer (OC) often presents at an advanced stage and is still one of the most frequent causes of gynecological cancer-related mortality worldwide. The nuclear factor erythroid-2 (NFE2) transcription factors include nuclear factor, erythroid 2 like 1 (NFE2L1), NFE2L2, and NFE2L3. NFE2 members bind to the antioxidant-response element (ARE) region and activate the expression of targeted genes. The distinct functions of NFE2 members in OC remain poorly elucidated. Several online bioinformatics databases were applied to determine gene expression, prognosis, mutations, and immune infiltration correlation in OC patients. NFE2L1 and NFE2L2 were decreased in OC, whereas NFE2L3 was increased. NFE2L2 and NFE2L3 were significantly correlated with the clinical stages of OC. High NFE2L1 level was significantly associated with short progression-free survival (PFS) in patients with OC ( HR = 1.18 , P = 0.021 ), while high NFE2L2 expression strongly correlated with long PFS ( HR = 0.77 , P = 0.00067 ). High NFE2L3 expression was associated with better overall survival and postprogression survival in OC. Functional analysis showed that NFE2 members mainly focused on transcription coactivator activities. Genetic alterations of NFE2 members were found in 13% of OC patients, and amplification ranked the top. The expression of NFE2 members was significantly correlated with immune infiltration of CD4+ T cells, CD8+ T cells, B cells, macrophages, and neutrophils in OC. Our study provides novel insights into the roles and prognostic potential of NFE2 family members in OC.

Double-loaded mature dendritic cell (DC) therapy for non-HLA-restricted patients with advanced ovarian cancer: Final results of a clinical phase I study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3052-3052 ◽  
Author(s):  
Marianne Imhof ◽  
Markus Lipovac ◽  
Lukas Angleitner-Boubenizek ◽  
Johannes Barta ◽  
Ivan Gomez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Responses ◽  
Immune Therapy ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Positive Trend ◽  
Clinical Phase ◽  
Dc Vaccine

3052 Background: Prognosis of ovarian cancer remains poor after initial responsiveness to surgery and chemotherapy followed by high recurrence and mortality rates and new experimental approaches are warranted. Our goal was to evaluate a novel DC-based vaccine, which exploits a unique dual loading strategy to amplify specific anti-tumor short- and long-term immune responses to delay or even prevent recurrent and metastatic disease. Methods: Monocytes were collected via apheresis, matured into DCs and pulsed with two universal tumor associated antigens (uTAA) in our GMP facility. DCs were loaded with TERT and Survivin via two different pathways (mRNA and peptide) to elicit CD8+ and CD4+T cells directly. Endpoints of the study were tolerability and safety, immunological and clinical responses. T cell responses against the IMP and loaded antigens were evaluated by cytokine bead array (CBA) and intracellular staining assays. Results: 15 non HLA-restricted patients with advanced ovarian cancer were enrolled 8 weeks after standard treatment (surgery and chemotherapy). Each patient was vaccinated intradermally on a weekly or fortnightly basis with a maximum of 8 doses of 13*106 double loaded DCs. The majority of treatment related side effects were grade 1 fever and erythema. Overall the therapy was well tolerated. Immune response data is available for 14/15 patients, 1 was withdrawn after the first administration. The IMP leads to strong immune responses with high frequency (>90%), which is proven for both uTAAs in CD8+ as well as CD4+ T cells. A clear positive trend in progression free survival is demonstrated compared to matched historical control. Conclusions: Therapy with our unique double loaded DC vaccine was feasible, safe and well-tolerated by patients. The vaccine was highly immune stimulatory and elicited both, long-term and short-term anti-tumor immune responses, establishing a promising platform for immune therapy for ovarian cancer and all solid tumors in general. The first two authors contributed equally. Clinical trial information: NCT01456065.

scholarly journals SPP1 is a Prognostic Related Biomarker and Correlated With Tumor-Infiltrating Immune Cells in Ovarian Cancer

2021 ◽  
Author(s):  
Wen Gao ◽  
Sheng Yin ◽  
Haiyan Sun ◽  
Zhuyan Shao ◽  
Peipei Shi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Vital Role ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Secreted Phosphoprotein 1

Abstract Background: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of some cancer types, but little is known whether it is a bystander or an actual player on driving immune infiltration in ovarian cancer.Methods: In this study, the expression of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and SPP1 immumohistochemical staining analysis was assessed by The HPA database. The clinical outcomes between SPP1 expression and ovarian cancer patients were evaluated via Kaplan-Meier Plotter and PrognoScan dataset. Immune infiltration analyses were explored using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database.Results: SPP1 was found overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter OS and PFS survivals. Particularly, elevated SPP1 expression was significantly associated with stage III ovarian cancer. Notably, SPP1 expression was positively correlated with infiltrating levels of CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression showed strong correlations with diverse immune hallmark sets in ovarian cancer. Of particular importance, functional enrichment analysis suggested that SPP1 strong related with immune response.Conclusions: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in ovarian cancer.Trial registration: Not applicable.

scholarly journals Expression Profiles and Prognostic Values of BOLA Family members in Ovarian Cancer

2020 ◽  
Author(s):  
Mingyang Zhu ◽  
Shiqi Xiao
Keyword(s):  
Ovarian Cancer ◽  
Metal Ion ◽  
Expression Profiles ◽  
Family Members ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Protein Disulfide Oxidoreductase

Abstract Background: The BOLA gene family, comprising 3 members, is mainly involved in the regulation of intracellular iron homeostasis. Emerging evidence suggests that BOLA family member 2 play vital roles in tumorigenesis and progression of hepatic cellular carcinoma. However, little known about its roles in ovarian cancer. Methods: In present study, we investigated the expression profiles, prognostic roles, and genetic alterations of three BOLA family members in patients with ovarian cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein–protein interaction networks of BOLA proteins and their interactors by using String database and Cytoscape software. In addition, we performed the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment by the Annotation, Visualization, and Integrated Discovery database. Finally, we explored the mechanisms underlying the involvement of BOLA family members in OC by using gene set enrichment analysis. Results: The mRNA and protein expression levels of BOLA2 and BOLA3 were heavily higher in ovarian cancer tissues than that in normal ovarian tissues. Dysregulated mRNA expressions of three BOLA family members were significantly associated with prognosis in overall or subgroup analysis. Moreover, genetic alterations also occurred in three BOLA family members in ovarian cancer. Network analysis and enrichment analysis indicated that three BOLA family members and their 20 interactors were mainly associated with metal-ion binding and protein disulfide oxidoreductase activity. Gene set enrichment analysis indicated that BOLA family members were mainly associated with oxidative phosphorylation, proteasome, protein export and glutathione metabolism in ovarian cancer. Conclusions: In brief, the present comprehensive bioinformatics analysis revealed that BOLA1, 2, and 3 may be new prognostic biomarkers, and BOLA2 and BOLA3 may be a potential therapeutic target of precision therapy for patients with ovarian cancer, but further studies are demanded to certify this notion.

scholarly journals CXCL13 Correlates with Prognosis, Immune Infiltration, and T Cell Exhaustion in Ovarian Cancer

2021 ◽  
Author(s):  
Hailing Duan ◽  
Ying Lv ◽  
Pan Liao ◽  
Yiming Wang ◽  
Zhifang Zheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Cell Adhesion ◽  
T Cell ◽  
Immune Cells ◽  
Gene Marker ◽  
T Cell Exhaustion ◽  
Cell Exhaustion ◽  
Immune Infiltration ◽  
Prognosis Prediction

Abstract Background: CXCL13 is an important chemotactic factor closely related to the biology of cancer cells. The presence work focused on exploring the significance of CXCL13 in prognosis prediction and analyzing the associations of CXCL13 with T cell function and immune infiltration in various cancers, especially ovarian cancer (OV).Purpose: CXCL13 is associated with prognosis, immune infiltration, and T cell failure of ovarian cancer.Methods: The Oncomine, GEPIA2 and HPA databases were utilized for analyzing CXCL13 levels within diverse cancers. The significance of CXCL13 in prognosis prediction was explored through Kaplan-Meier Plotter, TCGAportal, and GEPIA2. Meanwhile, the associations of CXCL13 with clinical stage, gene marker sets, and immune infiltration were examined through TISIDB, GEPIA2, and TIMER databases. Besides, CXCL13 was screened to analyze the biological processes (BPs) and KEGGs enriched by co-expression genes. The miRWalk database was employed for analyzing the gene-miRNA interaction network of CXCL13 within OV.Results: CXCL13 expression decreased in many cancers, which predicted the dismal survival of OV. CXCL13 upregulation was in direct proportion to the increased immune infiltration degrees of many functional T cells (like exhausted T cells) and immune cells. Additionally, some critical genes of exhausted T cells, such as TIM-3, PD-1, LAG3, TIGIT, GZMB, and CXCL13, were closely associated with CXCL13. Moreover, CXCL13 was related to immune response regulatory signaling pathway, leukocyte cell-cell adhesion, cell adhesion molecules (CAMs), and hematopoietic cell lineage. Conclusion: CXCL13 can serve as a biomarker to predict cancer prognosis, particularly OV. CXCL13 upregulation remarkably elevates the immune infiltration degrees of numerous immune cells, like mast cells, CD8+ T cells, natural killer (NK) cells, and dendritic cells (DCs). Furthermore, CXCL13 is suggested to be closely related to exhausted T cells, which may be used as a candidate regulating factor for T cell exhaustion within OV. Detecting CXCL13 levels contributes to prognosis prediction and CXCL13 regulation within exhausted T cells, which provides a new approach to maximizing the anti-OV efficacy of immunotherapy.

A phase I/IIa, open label, clinical trial evaluating the safety and efficacy of autologous T cells expressing enhanced TCRs specific for NY-ESO-1 in patients with recurrent or treatment refractory ovarian cancer (NCT01567891).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS3094-TPS3094
Author(s):  
Kunle Odunsi ◽  
Mihaela C. Cristea ◽  
Oliver Dorigo ◽  
Amir A. Jazaeri ◽  
Brian M. Slomovitz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
T Cells ◽  
Lentiviral Vector ◽  
Gynecologic Cancer ◽  
Progression Free Survival ◽  
Survival Duration ◽  
Open Label ◽  
Resistant Disease ◽  
Duration Of Response

TPS3094 Background: Epithelial ovarian cancer comprises the majority of malignant ovarian neoplasms (~80%) and is the leading cause of death from gynecologic cancer in the US. Due to lack of effective screening strategies, the majority (63%) of patients are diagnosed with ovarian cancer at advanced stages. New therapies are needed to address the unmet medical need of patients with ovarian cancer. 11-40% of ovarian cancers express NY-ESO-1 cancer testis/antigen. This study is evaluating affinity enhanced autologous NY-ESO-1c259T cells recognizing an NY-ESO-1 derived peptide complexed with HLA-A*02 in ovarian cancer. Methods: This single arm, open label clinical trial is evaluating safety and tolerability, antitumor activity (response rate by RECIST v1.1, progression free survival, overall survival, duration of response), and translational research endpoints. The study evaluates two lymphodepleting regimens: cyclophosphamide (enrolment completed; n = 7) and cyclophosphamide plus fludarabine (at least 10 subjects to be enrolled). Subjects must be ≥ 18 years old; HLA-A*02:01, *02:05, or *02:06 positive; have recurrent epithelial ovarian, primary peritoneal or fallopian tube carcinoma with refractory or platinum-resistant disease expressing NY-ESO-1 by IHC; have measurable disease; have ECOG status 0 or 1; and have adequate organ function. Following apheresis, the T cells are isolated and expanded with CD3/CD28 beads, transduced with a lentiviral vector containing the NY-ESO-1c259 TCR, and 1 – 6 × 109 transduced T cells are infused intravenously on Day 0 after lymphodepletion with fludarabine 30 mg/m2/day and cyclophosphamide 600 mg/m2/day on days -7 to -5. Response is assessed at weeks 4, 8, 12 and 24, and then every 3 months until confirmation of disease progression. Clinical trial information: NCT01567891.

scholarly journals Expression profiles and prognostic values of BolA family members in ovarian cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Mingyang Zhu ◽  
Shiqi Xiao
Keyword(s):  
Ovarian Cancer ◽  
Metal Ion ◽  
Expression Profiles ◽  
Family Members ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Protein Disulfide Oxidoreductase

Abstract Background The BOLA gene family, comprising three members, is mainly involved in regulating intracellular iron homeostasis. Emerging evidence suggests that BolA family member 2 plays a vital role in tumorigenesis and hepatic cellular carcinoma progression. However, there was less known about its role in ovarian cancer. Methods In the present study, we investigated the expression profiles, prognostic roles, and genetic alterations of three BolA family members in patients with ovarian cancer through several public databases, containing Oncomine and Gene Expression Profiling Interactive Analysis, Human Protein Atlas, Kaplan–Meier plotter and cBioPortal. Then, we constructed the protein-protein interaction networks of BOLA proteins and their interactors by using the String database and Cytoscape software. In addition, we performed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment by the Annotation, Visualization, and Integrated Discovery database. Finally, we explored the mechanisms underlying BolA family members’ involvement in OC by using gene set enrichment analysis. Results The mRNA and protein expression levels of BOLA2 and BOLA3 were heavily higher in ovarian cancer tissues than in normal ovarian tissues. Dysregulated mRNA expressions of three BolA family members were significantly associated with prognosis in overall or subgroup analysis. Moreover, genetic alterations also occurred in three BolA family members in ovarian cancer. GO analysis indicated that BolA family members might regulate the function of metal ion binding and protein disulfide oxidoreductase activity. Gene set enrichment analysis indicated that BolA family members were mainly associated with oxidative phosphorylation, proteasome, protein export, and glutathione metabolism in ovarian cancer. Conclusion In brief, our finding may contribute to increasing currently limited prognostic biomarkers and treatment options for ovarian cancer.

scholarly journals Phase I dose escalation safety and feasibility study of autologous WT1-sensitized T cells for the treatment of patients with recurrent ovarian cancer

2021 ◽  
Vol 9 (8) ◽  
pp. e002752
Author(s):  
Chrisann Kyi ◽  
Ekaterina Doubrovina ◽  
Qin Zhou ◽  
Sara Kravetz ◽  
Alexia Iasonos ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Phase I ◽  
Fallopian Tube ◽  
Dose Escalation ◽  
Cytotoxic T Lymphocyte ◽  
Wilms Tumor ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Maximum Tolerated Dose

BackgroundThis phase I dose escalation trial evaluated the feasibility of production, safety, maximum tolerated dose, and preliminary efficacy of autologous T cells sensitized with peptides encoding Wilms’ tumor protein 1 (WT1) administered alone or following lymphodepleting chemotherapy, in the treatment of patients with recurrent WT1+ ovarian, primary peritoneal, or fallopian tube carcinomas.MethodsA 3+3 dose escalation design was used to determine dose-limiting toxicity (DLT). In cohort I, patients received WT1-sensitized T cells dosed at 5×106/m2 (level I) without cyclophosphamide lymphodepletion. In cohorts II–IV, patients received lymphodepleting chemotherapy (a single intravenous dose of cyclophosphamide 750 mg/m2), 2 days prior to the first intravenous infusion of WT1-sensitized T cells administered at escalating doses (2×107/m2 (level II), 5×107/m2 (level III), and 1×108/m2 (level IV)).ResultsTwelve patients aged 23–72 years, with a median of 7 prior therapies (range 4–14), were treated on the study. No DLT was observed, even at the highest dose level of 1×108/m2 WT1-sensitized T cells tested. Common adverse events reported were grade 1–2 fatigue, fever, nausea, and headache. Median progression-free survival (PFS) was 1.8 months (95% CI, 0.8 to 2.6); 1 year PFS rate 8.3% (95% CI, 0.5 to 31.1). Median overall survival (OS) was 11.0 months (95% CI, 1.1 to 22.6); OS at 1 year was 41.7% (95% CI, 15.2% to 66.5%). Best response was stable disease in one patient (n=1) and progressive disease in the others (n=11). We observed a transient increase in the frequencies of WT1-specific cytotoxic T lymphocyte precursors (CTLp) in the peripheral blood of 9 of the 12 patients following WT1-sensitized T-cell infusion.ConclusionWe demonstrated the safety of administration of WT1-sensitized T cells and the short-term increase in the WT1 CTLp. However, at the low doses evaluated we did not observe therapeutic activity in recurrent ovarian cancer. In this heavily pretreated population, we encountered challenges in generating sufficient numbers of WT1-reactive cytotoxic T cells. Future studies employing WT1-specific T cells generated from lymphocytes are warranted but should be done earlier in the disease course and prior to intensive myelosuppressive therapy.Trial registration numberNCT00562640.One-sentence summaryThe authors describe the first human application of autologous WT1-sensitized T cells in the treatment of patients with recurrent ovarian, primary peritoneal, and fallopian tube carcinomas.

scholarly journals Comprehensive Analysis of the Expression, Prognostic Value and Correlations with Immune Infiltration of PBX Family Members in Colorectal Cancer

2021 ◽  
Author(s):  
Yanping Hu ◽  
Yihang Shen
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Interaction Analysis ◽  
Family Members ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Immune Infiltration ◽  
Colorectal Cancer Patients

Abstract Background: Colorectal cancer is the third commonest cancer and the second leading cause of cancer deaths globally. The Pre-B-cell leukemia transcription factor (PBX) family plays an essential biological role in the growth and development of the organism. PBX genes have been found to be implicated in the tumorigenesis of a variety of human tumors through multiple pathways, but its function in colorectal cancer is unclear. Methods: The expression pattern, prognostic value and relationship with immune infiltration of PBX genes in patients with colorectal cancer were investigated using the Oncomine, GEPIA, Kaplan-Meier Plotter and TIMER databases. In addition, gene mutation and interaction analysis of PBX family members in colorectal cancer patients using cBioPortal and GeneMANIA databases, respectively.Results: We revealed that a significantly lower expression level of PBX1, PBX2 and PBX3 in colorectal cancer tissues than in normal tissues, and the expression levels of PBX1 and PBX2 were significantly correlated with clinical tumor stage. Furthermore, survival analysis showed that high transcript levels of PBX4 were associated with overall survival in colon cancer patients, while low levels of PBX2 predicted improved disease-free survival in rectal cancer patients. In addition, in colon and rectal cancers, PBX proteins were notably associated with infiltration of multiple immune cells, including CD4+ T cells, CD8+ T cells, macrophages, neutrophils, B cells, and dendritic cells.Conclusion: These findings implies that PBX1 and PBX3 are potential targets for precision therapy of colorectal cancer patients and that PBX2 and PBX4 may be new prognostic markers for colorectal cancer patients.

The role of proinflammatory immune (IFN-gamma) gene signature in predicting prognosis and response to chemotherapy in uterine carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14209-e14209
Author(s):  
Haider Mahdi ◽  
Peter Graham Rose ◽  
Fadi W Abdul-Karim ◽  
Bradley J. Monk ◽  
Ying Ni
Keyword(s):  
Gene Expression ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Progression Free Survival ◽  
Gene Signature ◽  
Free Survival ◽  
High Stage ◽  
Response To Chemotherapy ◽  
Ifn Γ

e14209 Background: Immunotherapy is promising option given low toxicity and potential durable response. In mismatch repair proficient endometrial and ovarian cancers, the reported response rate is ranging from 10-15% in recurrent setting. We need to better identify subset of patients who benefits from immunotherapy. Multigene immune signatures represent a robust means of capturing a complex, T cell–inflamed phenotype necessary for the clinical activity of PD-1–/PD-L1–directed monoclonal antibodies. IFN-γ is a key cytokine produced by activated T cells, as well as natural killer (NK) and NK T cells, in the tumor microenvironment. An immune-related IFN-γ 18-gene profile was derived through a cross-validated penalized regression modeling strategy to predict response to anti-PD1 therapy across 9 different tumor types. We want to test if this gene panel can also predict cancer outcome and response to chemotherapy. Methods: We used whole transcriptome sequencing of RNA matched tumor-normal samples from 38 high stage (Stage III and IV) uterine serous cancer patients. All patients received chemotherapy with platinum and taxanes. IFN-18 gene expression score was calculated by averaging the normalized and log transformed individual gene read counts. The optimized score cut off was selected to best separating the progression free survival. Then the cut off score was tested in The Cancer Genomic Atlas (TCGA) uterine and ovarian cancer RNAseq datasets. Results: The IFN score of 2.46 was determined based on 18-gene expression derived from 38 high-stage uterine serous cancer samples. Average age was 67 years (range: 56-82 years). Uterine serous cancer is known to be MSI stable. Patients with score higher than 2.46 showed significantly longer progression free survival (PFS – 57.6 months vs 15months, p = 0.002) and longer overall survival (73.1 months vs 51.1 months), not statistically significant given our small sample size, p = 0.13) compared to the patients with score lower than 2.46. Then this IFN based gene signature was then applied to TCGA 541 uterine cancer samples with RNAseq data. Similarly, this signature predicted significant improvement in both progression-free survival (p = 0.001) and overall survival (p = 0.005). Interestingly, this score cannot separate outcome for TCGA ovarian cancer cohort. Conclusions: Immune-related IFN-γ gene signature predicted prognosis and response to chemotherapy. We plan to assess if this signature will predict endometrial cancer patients who benefits from anti-PD1 therapy.

scholarly journals LncRNA PAXIP1-AS1 is a Prognostic Biomarker and Correlated with Immune Infiltrates in Ovarian Cancer

2021 ◽  
Author(s):  
Buze Chen ◽  
Xiaoyuan Lu ◽  
Qingmei Zhou ◽  
Qing Chen ◽  
Siyan Zhu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Signaling Pathway ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
Th2 Cells ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
The Relationship

Abstract Background: 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. Methods: QRT-PCR, 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. Results: 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). And 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 may inhibit the function of aDC, B cells, CD8 T cells, Cytotoxic cells, DC, iDC, Macrophages, Mast cells, Neutrophils, NK CD56dim cells, T cells, TFH, Tgd, Th1 cells, Th2 cells and Treg. Conclusions: Low expression of PAXIP1-AS1 was significantly associated with poor survival and immune infiltration in OC. PAXIP1-AS1 could be a promising prognosis biomarker for OC.

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