Roles of PPAR activation in cancer therapeutic resistance: Implications for combination therapy and drug development.

Therapeutic resistance is a major obstacle to successful treatment or effective containment of cancer. Peroxisome proliferator-activated receptors (PPARs) play an essential role in regulating energy homeostasis and determining cell fate. Despite of the pleiotropic roles of PPARs in cancer, numerous studies have suggested their intricate relationship with therapeutic resistance in cancer. In this review, we provided an overview of the roles of excessively activated PPARs in promoting resistance to modern anti-cancer treatments, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. The mechanisms through which activated PPARs contribute to therapeutic resistance in most cases include metabolic reprogramming, anti-oxidant defense, anti-apoptosis signaling, proliferation-promoting pathways, and induction of an immunosuppressive tumor microenvironment. In addition, we discussed the mechanisms through which activated PPARs lead to multidrug resistance in cancer, including drug efflux, epithelial-to-mesenchymal transition, and acquisition and maintenance of the cancer stem cell phenotype. Preliminary studies investigating the effect of combination therapies with PPAR antagonists have suggested the potential of these antagonists in reversing resistance and facilitating sustained cancer management. These findings will provide a valuable reference for further research on and clinical translation of PPAR-targeting treatment strategies.

Age-Period-Cohort Analysis on Long-Term Mortality Trend of Genitourinary Diseases - China, 1987-2021.

What is already known about this topic?: There has been a lack of attention to genitourinary diseases for an extended period, resulting in limited research on the mortality trends of genitourinary diseases in China. What is added by this report?: This study examines the long-term trend of genitourinary diseases' mortality across Chinese individuals of all genders and in various urban and rural regions. Additionally, it investigates the impact of age-period-cohort effects on this trend. What are the implications for public health practice?: It is imperative to address genitourinary diseases, particularly among vulnerable populations such as rural older men. Policymakers should prioritize these individuals by providing necessary policy interventions and healthcare support.

Consequences of China's special send-down movement on infectious disease control in rural areas: a natural experiment.

Background: China's send-down movement in the 1960s and 1970s, as a natural experiment, provides a unique opportunity to investigate the relationship between peers' dissemination of health literacy, community health workers, and infectious disease control in areas with weak health systems and inadequate human resources. To address the lack of studies on the health effects of the send-down movement, this study examined the associations between prenatal exposure to the send-down movement and infectious diseases in China. Methods: We analyzed 188,253 adults born in 1956-1977 with rural hukou who participated in the Second National Sample Survey on Disability in 2006 across 734 counties of China. Difference-in-difference models were used to detect the effect of the send-down movement on infectious diseases. Infectious diseases were ascertained by using the combination of self- or family members' reports and on-site medical diagnosis of disabilities attributed to infectious disease by experienced specialists. The density of the relocated urban sent-down youth or "sent-down youths" (SDYs) in each county defined the intensity variable of the send-down movement. Results: Individuals in SDY-receiving areas with increased intensity of prenatal exposure to the send-down movement had a decreased probability of infectious diseases (ß = -0.0362, 95% CI: 0.0591, -0.0133) after controlling for a set of regional and cohort characteristics. This association was stronger in counties with more prevalent infectious diseases prior to the send-down movement (ß = -0.0466, 95% CI: 0.0884, -0.0048) than in those with less prevalence (ß = -0.0265, 95% CI: 0.0429, -0.010). No substantial differences were found across sex-specific groups or by strictness of send-down movement implementation. On average, prenatal exposure to the send-down movement corresponded to a decrease in the probability of infectious diseases in rural areas by 19.70%. Conclusions: For areas with weak health systems, strengthening community health workers and promoting health literacy may be two key points to address the burden of infectious diseases. Increasing education and primary health care through peer-to-peer dissemination may contribute to the reduction of infectious disease prevalence.

Corrigendum: A potential indicator ARRDC2 has feasibility to evaluate prognosis and immune microenvironment in ovarian cancer.

[This corrects the article DOI: 10.3389/fgene.2022.815082.].

A Potential Indicator ARRDC2 Has Feasibility to Evaluate Prognosis and Immune Microenvironment in Ovarian Cancer.

Background: The abnormal expression of α-arrestin protein family plays a key regulatory role in the occurrence and development of many cancers, including colorectal cancer and cervical cancer, and is inseparable from changes in the tumor immune microenvironment. However, the role of ARRDC2, an important member of this family, in the malignant biological process of ovarian cancer (OC) has not been reported, and its role in the change of the immune microenvironment is also unknown. Methods: In this study, HPA, TCGA, GEO and other databases were used to explore the role of ARRDC2 in the prognosis assessment of ovarian cancer. Then, GO, KEGG analysis and GSEA analysis of the biological processes and cell signaling pathways that ARRDC2 may be involved in activated or inhibited. In addition, the TIMER and TISIDB database were used to conduct in-depth research on the role of ARRDC2 in the change of the immune microenvironment of ovarian cancer. The CMap database explored and screened drugs that may be used for treatment. Through cell transfection, CCK-8, Ki-67 immunofluorescence, wound healing, transwell and clone formation assay, the effect of ARRDC2 knockdown on the malignant biological behavior of OC cells were explored. Results: There were significant differences between OC and ARRDC2 mRNA and protein levels. High ARRDC2 expression level is associated with poor overall survival and can be used as an independent prognostic factor. Interestingly, ARRDC2 expression is positively correlated with B cells, Neutrophils, Dendritic cells and CD8+ T cells, signifying that ARRDC2 may be related to infiltration of immune cells. ARRDC2 and its co-expressed genes are enriched in cell signaling pathways related to the immune system. We explored two possible drugs for the treatment of ovarian cancer. Finally, the results of in vitro experiments indicated that knockdown of ARRDC2 may inhibit malignant phenotypes such as proliferation and migration of OC cells. Conclusion: The differentially expressed ARRDC2 may be a potential prognostic indicator and can be used as a novel biomarker for exploring the immune microenvironment of ovarian cancer.

Antibody-conjugated silica-coated gold nanoparticles in targeted therapy of cervical cancer.

This study aimed to synthesize silica-coated gold (Au@SiO2) nanoparticles coupled to antibodies against the scavenger receptor class B type I (SR-BI) and investigate their potential ability of visual tracking and treatment of cervical cancer. The fluorescein isothiocyanate (FITC)-labeled Au@SiO2-SR-BI antibody was synthesized, followed by characterization determination. The expression and location of SR-BI protein in cervical cancer cells were respectively detected by western blot and immunofluorescence assays. The effects of nanoparticles on cancer cells were determined by adsorption assay and apoptosis detection, respectively. The effects of nanoparticles on tumor formation in nude mice were determined. The particle sizes of Au@SiO2 ranged from 2-2.5 µm, and the particle size distribution was relatively uniform. MS751 showed the highest expression of SR-BI. SR-BI was located in the cytomembrane. There were more FITC-Au@SiO2-SR-BI nanoparticles on the surface of the cells compared to FITC-Au@SiO2. Significant apoptosis was observed in the FITC-Au@SiO2-SR-BI-treated group in both MS751 and H8 cells. Photothermal ablation of solid tumors was observed when FITC-Au@SiO2-SR-BI was activated using 808 nm wave. Expressions of the apoptosis-related markers including BCL2, BCLX, and p-AKT were significantly decreased, while those of caspase 3 and caspase 8 were significantly increased. The study presented a novel antibody-conjugated Au@SiO2 nanoparticle specifically targeting molecular receptors on cancer cell membranes. Antibody-conjugated Au@SiO2 nanoparticles may have therapeutic potential for the treatment of cervical cancer.

LOC100130075 Promotes Cervical Cancer Progression by Activating MDM2 Transcription through E2F1.

Cervical cancer (CC) represents one of the most frequent gynecological tumors worldwide and it takes a big part in cancer-related deaths in women. The mouse double minute 2 (MDM2) gene has been elucidated to be deregulated in cancers and exert its oncogenic activity. Through ENCODE ( https://www.encodeproject.org/ ), LOC100130075 was discovered to be a nearby gene of MDM2. Emerged as a novel long non-coding RNA (lncRNA), LOC100130075 has not been studied in cancers. Therefore, we aim to figure out the function of LOC100130075 and its interaction with MDM2 in CC progression. The high expression pattern of LOC100130075 and MDM2 and a positive correlation between them were firstly verified in CC cells. Then, it was verified that LOC100130075 interference suppressed the proliferation and enhanced the apoptosis of CC cells. Furthermore, we verified through mechanism assays including ChIP, RNA pull-down, as well as luciferase reporter assays that LOC100130075 bound to E2F transcription factor 1 (E2F1) to activate MDM2 transcription. Furthermore, the result of rescue assays manifested that MDM2 overexpression reversed the inhibitory function of LOC100130075 deficiency on CC development. In a word, LOC100130075 promoted CC malignancy by activating MDM2 transcription through E2F1, which may provide a new direction in the advancement of CC treatments.

Immune Characteristics Analysis and Transcriptional Regulation Prediction Based on Gene Signatures of Chronic Obstructive Pulmonary Disease.

PURPOSE: The variation in inflammation in chronic obstructive pulmonary disease (COPD) between individuals is genetically determined. This study aimed to identify gene signatures of COPD through bioinformatics analysis based on multiple gene sets and explore their immune characteristics and transcriptional regulation mechanisms. METHODS: Data from four microarrays were downloaded from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs) between COPD patients and controls. Weighted gene co-expression network analysis was applied to identify trait-related modules and then select key module-related DEGs. The optimized gene set of signatures was obtained using the least absolute shrinkage and selection operator (LASSO) regression analysis. The CIBERSORT algorithm and Pearson correlation test were used to analyze the relationship between gene signatures and immune cells. Finally, public databases were used to predict the transcription factors (TFs) and upstream miRNAs. RESULTS: A total of 127 DEGs in COPD were identified from the combined dataset. By considering the intersection of DEGs and genes in two trait-related modules, 83 key module-related DEGs were identified, which were mainly enriched in interleukin-related pathways. Seven-gene signatures, including MTHFD2, KANK3, GFPT2, PHLDA1, HS3ST2, FGG, and RPS4Y1, were further selected using the LASSO algorithm. These gene signatures showed the predictive potential for COPD risks and were significantly correlated with 18 types of immune cells. Finally, nine miRNAs and three TFs were predicted to target MTHFD2, GFPT2, PHLDA1, and FGG. CONCLUSION: We proposed the seven-gene-signature to predict COPD risk and explored its potential immune characteristics and regulatory mechanisms.

[To design an intelligent analysis platform for the disabled population data].

OBJECTIVE: To design demand-oriented intelligent analysis platform framework for the disabled population data from overall management to security. METHODS: DATAI-WebEx, active learning, Browser/Server architecture, role-role-based access control, Bayesian network, GIS analysis technology, cluster analysis, regression analysis and other intelligent technologies were used in this study, which provided the functions of multi-source heterogeneous disabled population data fusion, intelligent analysis, secure access and data sharing. RESULTS: The disability data warehouse and intelligent analysis platform can realize the structured and unstructured information disabled population data alignment and data fusion. Also, it can provide disability risk module clustering, disability risk factor identification, disabled distribution analysis, disability scale dynamic trajectory prediction, early warning, disability grade development. Moreover, it can provide a guarantee for the safe and convenient access of sensitive data with the support of "classified boxes", and realize the safe sharing of data of the disabled population. CONCLUSION: The disability data warehouse and intelligent analysis platform can provide the services of "comprehensive fusion-intelligent mining-safe sharing".

Integrated analysis of immune-related genes in endometrial carcinoma.

BACKGROUND: Exploring novel and sensitive targets is urgent due to the high morbidity of endometrial cancer (EC). The purpose of our study was to explore the transcription factors and immune-related genes in EC and further identify immune-based lncRNA signature as biomarker for predicting survival prognosis. METHODS: Transcription factors, aberrantly expressed immune-related genes and immune-related lncRNAs were explored through bioinformatics analysis. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify the immune and overall survival (OS) related lncRNAs. The accuracy of model was evaluated by Kaplan-Meier method and receiver operating characteristic (ROC) analysis, and the independent prognostic indicator was identified with Cox analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to detect the accuracy of our results. RESULTS: A network of 29 transcription factors and 17 immune-related genes was constructed. Furthermore, four immune-prognosis-related lncRNAs were screened out. Kaplan-Meier survival analysis and time-dependent ROC analysis revealed a satisfactory predictive potential of the 4-lncRNA model. Consistency was achieved among the results from the training set, testing set and entire cohort. The distributed patterns between the high- and low-risk groups could be distinguished in principal component analysis. Comparisons of the risk score and clinical factors confirmed the four-lncRNA-based signature as an independent prognostic indicator. Last, the reliability of the results was verified by qRT-PCR in 29 cases of endometrial carcinoma and in cells. CONCLUSIONS: Overall, our study constructed a network of transcription factors and immune-related genes and explored a four immune-related lncRNA signature that could serve as a novel potential biomarker of EC.

Long non-coding RNA CTBP1-AS2 enhances cervical cancer progression via up-regulation of ZNF217 through sponging miR-3163.

BACKGROUND: Long non-coding RNAs (lncRNAs) play significant roles in tumorigenesis and can contribute to identification of novel therapeutic targets for cancers. This paper was aimed at exploring the role of CTBP1 divergent transcript (CTBP1-AS2) in cervical cancer (CC) progression. METHODS: qRT-PCR and western blot assays were used to detect relevant RNA and protein expressions. In vitro functional assays, including CCK8, EdU, TUNEL and transwell assays were applied to explore the functions of CTBP1-AS2 in CC cell proliferation, apoptosis and migration. In vivo animal study was utilized to investigate the role of CTBP1-AS2 in tumor growth. Luciferase reporter, RNA pull down and RIP assays were performed to determine the specific mechanical relationship between CTBP1-AS2, miR-3163 and ZNF217. RESULTS: CTBP1-AS2 was significantly overexpressed in CC cell lines. Knockdown of CTBP1-AS2 curbed cell proliferation, migration and invasion, while stimulated cell apoptosis in vitro. CTBP1-AS2 facilitated xenograft tumor growth in vivo. Cytoplasmic CTBP1-AS2 was found to be a miR-3163 sponge in CC cells. MiR-3163 inhibition abolished the anti-tumor effects of CTBP1-AS2 knockdown. Additionally, Zinc finger protein 217 (ZNF217) was identified as a direct target of miR-3163. CTBP1-AS2 acted as a miR-3163 sponge to elevate ZNF217 expression. ZNF217 up-regulation abrogated the tumor suppressing effects of CTBP1-AS2 knockdown. CONCLUSION: CTBP1-AS2 regulates CC progression via sponging miR-3163 to up-regulate ZNF217.

Identification of lysine acetylome in cervical cancer by label-free quantitative proteomics.

BACKGROUND: Lysine acetylation is a post-translational modification that regulates a diversity of biological processes, including cancer development. METHODS: Here, we performed the quantitative acetylproteomic analysis of three primary cervical cancer tissues and corresponding adjacent normal tissues by using the label-free proteomics approach. RESULTS: We identified a total of 928 lysine acetylation sites from 1547 proteins, in which 495 lysine acetylation sites corresponding to 296 proteins were quantified. Further, 41 differentially expressed lysine acetylation sites corresponding to 30 proteins were obtained in cervical cancer tissues compared with adjacent normal tissues (Fold change > 2 and P < 0.05), of which 1 was downregulated, 40 were upregulated. Moreover, 75 lysine acetylation sites corresponding to 58 proteins were specifically detected in cancer tissues or normal adjacent tissues. Motif-X analysis showed that kxxxkxxxk, GkL, AxxEk, kLxE, and kkxxxk are the most enriched motifs with over four-fold increases when compared with the background matches. KEGG analysis showed that proteins identified from differently and specifically expressed peptides may influence key pathways, such as Notch signaling pathway, viral carcinogenesis, RNA transport, and Jak-STAT, which play an important role in tumor progression. Furthermore, the acetylated levels of CREBBP and S100A9 in cervical cancer tissues were confirmed by immunoprecipitation (IP) and Western blot analysis. CONCLUSIONS: Taken together, our data provide novel insights into the role of protein lysine acetylation in cervical carcinogenesis.

Effect of hyperoside on cervical cancer cells and transcriptome analysis of differentially expressed genes.

BACKGROUND: Hyperoside (Hy) is a plant-derived quercetin 3-d-galactoside that exhibits inhibitory activities on various tumor types. The objective of the current study was to explore Hy effects on cervical cancer cell proliferation, and to perform a transcriptome analysis of differentially expressed genes. METHODS: Cervical cancer HeLa and C-33A cells were cultured and the effect of Hy treatment was determined using the Cell Counting Kit-8 (CCK-8) assay. After calculating the IC50 of Hy in HeLa and C-33A cells, the more sensitive to Hy treatment cell type was selected for RNA-Seq. Differentially expressed genes (DEGs) were identified by comparing gene expression between the Hy and control groups. Candidate genes were determined through DEG analysis, protein interaction network (PPI) construction, PPI module analysis, transcription factor (TF) prediction, TF-target network construction, and survival analysis. Finally, the key candidate genes were verified by RT-qPCR and western blot. RESULTS: Hy inhibited HeLa and C33A cell proliferation in a dose- and time-dependent manner, as determined by the CCK-8 assay. Treatment of C-33A cells with 2 mM Hy was selected for the subsequent experiments. Compared with the control group, 754 upregulated and 509 downregulated genes were identified after RNA-Seq. After functional enrichment, 74 gene ontology biological processes and 43 Kyoto Encyclopedia of Genes and Genomes pathways were obtained. According to the protein interaction network (PPI), PPI module analysis, TF-target network construction, and survival analysis, the key genes MYC, CNKN1A, PAX2, TFRC, ACOX2, UNC5B, APBA1, PRKACA, PEAR1, COL12A1, CACNA1G, PEAR1, and CCNA2 were detected. RT-qPCR was performed on the key genes, and Western blot was used to verify C-MYC and TFRC. C-MYC and TFRC expressions were lower and higher than the corresponding values in the control group, respectively, in accordance with the results from the RNA-Seq analysis. CONCLUSION: Hy inhibited HeLa and C-33A cell proliferation through C-MYC gene expression reduction in C-33A cells and TFRC regulation. The results of the current study provide a theoretical basis for Hy treatment of cervical cancer.

Quercetin-Modified Metal-Organic Frameworks for Dual Sensitization of Radiotherapy in Tumor Tissues by Inhibiting the Carbonic Anhydrase IX.

The development of multifunctional nanoscale radiosensitizers has attracted a tremendous amount of attention, which can enhance the radiosensitization of tumor tissues and reduce unnecessary damage to the surrounding organs. However, the persistent hypoxia environment within the tumor limits their applications in radiotherapy. In this paper, a stable nanocomposite was engineered to overcome the hypoxia properties by using 1,4-benzenedicarboxylic acid produced from a Zr-MOF as a carbonic anhydrase IX (CA IX) inhibitor and quercetin (QU) as a radiosensitizer. QU was encapsulated into the Zr-MOF structure to achieve a synergetic dual sensitization therapy. Zr-MOF-QU exhibits an excellent potential of radiotherapy sensitization characteristics in vitro and in vivo from the γ-H2AX immunofluorescence staining and colony assays. The mechanisms of alleviating hypoxia-induced resistance and sensitizing tumor tissues to improve cell apoptosis from radiation were found to suppress CA IX expressions by the decomposition product from Zr-MOF and boost the sensitivity by QU in radiation therapy. Moreover, there was no significant systemic toxicity during the treatment, and the therapeutic outcome was assessed in animal models. Therefore, our results demonstrate a promising cancer treatment approach in the radiation field.

Expression and clinicopathological significance of hematopoietic pre-B cell leukemia transcription factor-interacting protein in cervical carcinoma.

Hematopoietic pre-B-cell leukemia transcription factor(PBX)-interacting protein (HPIP) is overexpressed in various malignancies, but its role in cervical cancer (CC) remains unknown. This study investigated the correlations of HPIP expression with clinicopathological factors and prognosis of cervical carcinoma patients. Expression of HPIP was detected in CC from 167 patients along with 45 corresponding normal cervical specimens by immunohistochemistry. HPIP immunoreactivity was overexpressed in CC cases compared with that in normal endometrium (P < 0.05). High HPIP expression was positively correlated with FIGO stage, histological grade, lymph node metastasis and recurrence (P < 0.05). Patients with high HPIP expression exhibited significantly poorer overall survival (OS) and disease-free survival (DFS) than patients with low HPIP expression (both P < 0.001). Cox multivariate analysis showed that high HPIP expression was an independent prognostic factor for both OS [hazard ratio (HR) = 8.791, 95% confidence interval (CI) = 2.098-36.826; P = 0.003 and DFS of patients with CC (HR = 10.485, 95% CI = 2.512-36.826; P = 0.001)]. We identified HPIP protein expression as a novel independent poor prognostic indicator in CC.

A water-soluble polysaccharide from the roots of Polygala tenuifolia suppresses ovarian tumor growth and angiogenesis in vivo.

PTP, one polysaccharide extracted from the roots of Polygala tenuifolia, has displayed anti-cancer activity in several types of ovarian cancer cells. This study aims to elucidate the structure of PTP and investigate its anticancer effects against SKOV3 xenograft tumor growth in BALB/c mice, as well as the underlying mechanisms involved. GC-MS and NMR data indicate that PTP has a backbone composed of 1,4,6-linked-ß-Galp, 1,4-linked-ß-Galp and 1,4-linked-ß-Glcp, with non-reducing terminal 1-linked-α-Glcp attached to O-6 of 1,4,6-linked-ß-Galp. The tumor growth was suppressed in mice following two week's PTP administration (10, 20 and 40mg/kg) due to the induction of apoptosis, as detected by TUNEL assay. Moreover, lower serum VEGF and EGFR levels were observed in BALB/c mice treated with different doses of PTP when compared with that in untreated mice. Also, EGFR, VEGF, and CD34 were decreased in both transcript and protein levels in the tumor-bearing mice upon PTP treatment. Taken together, our data suggest that PTP appears to be a powerful chemopreventive agent for the patients with ovarian cancer, especially at advanced stage.

Identification of Subpathway Signatures For Ovarian Cancer Prognosis by Integrated Analyses of High-Throughput miRNA and mRNA Expression.

BACKGROUND/AIMS: Ovarian cancer (OC) causes more death and serious conditions than any other female reproductive cancers, and many expression signatures have been identified for OC prognoses. However, no significant overlap is found among signatures from different studies, indicating the necessity of signature identifications at the functional level. METHODS: We performed an integrated analyses of miRNA and gene expressions to identify OC prognostic subpathways (pathway regions). Using The Cancer Genome Atlas data set, we identified core prognostic subpathways, and calculated subpathway risk scores using both miRNA and gene components. Finally, we performed global risk impact analyses to optimize core subpathways using the random walk algorithm. RESULTS: Subpathway-level analyses displayed more robust results than the gene- and miRNA-level analyses. Moreover, we verified the advantage of core subpathways over the entire pathway-based results and their prognostic performance in two independent validation data sets. Based on the global impact score, 13 subpathway signatures were selected and a combined subpathway-based risk score was further calculated for OC patient prognoses. CONCLUSIONS: Overall, it was possible to systematically perform integrated analyses of the expression levels of miRNAs and genes to identify prognostic subpathways and infer subpathway risk scores for use in OC clinical applications.

Expression profiles analysis reveals an integrated miRNA-lncRNA signature to predict survival in ovarian cancer patients with wild-type BRCA1/2.

Emerging evidence shows that dysregulated expression of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were closely linked with disease progression, including cancers. However, the joint predictive power of miRNAs and lncRNAs in prognosis for ovarian cancer (OV) patients with wild-type BRCA1/2 is as yet unknown. In this study, we sought to assess the joint predictive power of miRNAs and lncRNAs by integrating miRNA and lncRNA expression profiles and clinical data of 281 OV patients with wild-type BRCA1/2 from The Cancer Genome Atlas (TCGA) project. Finally, we identified an integrated miRNA-lncRNA signature composing of two lncRNAs (LINC01234 and CCDC144NL-AS1) and two miRNAs (miR-637 and miR-129-5p) which can effectively classify OV patients with wild-type BRCA1/2 into groups with the good and poor outcome. The prognostic value of the integrated miRNA-lncRNA signature was validated in the testing cohort and entire TCGA cohort. Multivariate analysis demonstrated the independence of the integrated miRNA-lncRNA signature of known other clinical factors. Further analysis suggested that patients who were in the low-risk group based on the signature achieved a better CR from platinum-based chemotherapy compared with patients in the high-risk group. Our results indicated that this integrated miRNA-lncRNA signature may have important clinical implications for risk stratification of ovarian cancer patients with wild-type BRCA1/2.

Expression of HPIP in epithelial ovarian carcinoma: a clinicopathological study.

OBJECTIVES: Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP) plays an important role in cancer invasion and metastasis. The aim of this study is to investigate the expression of HPIP in epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Immunohistochemical method was performed using 42 normal ovarian specimens and 145 specimens with EOC. The correlations of HPIP expression with the clinicopathological factors and prognosis of EOC patients were evaluated. Statistical analyses were performed using the chi-square test, multivariate Cox proportional hazard, and Kaplan-Meier method. RESULTS: HPIP expression in EOC was higher than that in normal tissues (P<0.001). HPIP expression was significantly associated with histological grade, International Federation of Gynecology and Obstetrics stage, and lymphatic metastasis of EOC (P<0.05). Patients with high HPIP expression had poorer overall survival and disease-free survival (P<0.001) compared with patients with low HPIP expression. Multivariate Cox analysis demonstrated that HPIP was an independent factor for overall survival and disease-free survival (P<0.05). CONCLUSION: HPIP may be a valuable biomarker for predicting the prognosis of EOC patients and may serve as a potential target for cancer therapy.