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1.
Background: Esophageal cancer (ESCA) is one of the most commonly diagnosed cancers in the world. Tumor immune microenvironment is closely related to tumor prognosis. The present study aimed at analyzing the competing endogenous RNA (ceRNA) network and tumor-infiltrating immune cells in ESCA.Methods: The expression profiles of mRNAs, lncRNAs, and miRNAs were downloaded from the Cancer Genome Atlas database. A ceRNA network was established based on the differentially expressed RNAs by Cytoscape. CIBERSORT was applied to estimate the proportion of immune cells in ESCA. Prognosis-associated genes and immune cells were applied to establish prognostic models basing on Lasso and multivariate Cox analyses. The survival curves were constructed with Kaplan–Meier method. The predictive efficacy of the prognostic models was evaluated by the receiver operating characteristic (ROC) curves.Results: The differentially expressed mRNAs, lncRNAs, and miRNAs were identified. We constructed the ceRNA network including 23 lncRNAs, 19 miRNAs, and 147 mRNAs. Five key molecules (HMGB3, HOXC8, HSPA1B, KLHL15, and RUNX3) were identified from the ceRNA network and five significant immune cells (plasma cells, T cells follicular helper, monocytes, dendritic cells activated, and neutrophils) were selected via CIBERSORT. The ROC curves based on key genes and significant immune cells all showed good sensitivity (AUC of 3-year survival: 0.739, AUC of 5-year survival: 0.899, AUC of 3-year survival: 0.824, AUC of 5-year survival: 0.876). There was certain correlation between five immune cells and five key molecules.Conclusion: The present study provides an effective bioinformatics basis for exploring the potential biomarkers of ESCA and predicting its prognosis.  相似文献   

2.
BackgroundLong noncoding RNAs (lncRNAs) have gain increasing attention in lung adenocarcinoma. In this study, we aimed at constructing and analyzing the lncRNAs and the related proteins based competitive endogenous RNA (ceRNA) network.MethodsRNA expression data of lung adenocarcinoma were extracted from the TCGA database. Differentially expressed (DE) lncRNAs, messenger RNAs (mRNAs) and microRNAs (miRNAs) were identified and then a DElncRNA-DEmiRNA-DEmRNA ceRNA network was constructed for lung adenocarcinoma. We also analyzed the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the DEgenes. Kaplan-Meier survival curves were also been further utilized for exploring the prognostic factors.ResultsAfter compared and calculated lncRNA, mRNA and miRNA expression profiles between lung adenocarcinoma and normal samples, 1709 differential expressed lncRNAs, 2554 differential expressed mRNAs and 116 differential expressed miRNAs were finally identified. Afterwards, a lncRNA mediated ceRNA network was constructed, according to the interactions among 544 pairs of DElncRNA-DEmiRNA relationships and 47 pairs of DEmiRNA-DEmRNA relationships. As for the survival analyses, we found 10 DElncRNAs, 25 DEmRNAs and 7 miRNAs have statistically prognostic significance for overall survival, respectively.ConclusionsThis study provides meaningful information for deeper understanding the underlying molecular mechanism of lung adenocarcinoma and for evaluating prognosis, which could monitor recurrence, guide clinical treatment drugs and subsequent related researches.  相似文献   

3.
As essential regulators of gene expression, miRNAs are engaged in the initiation and progression of colorectal cancer (CRC), including antitumour immune response. In this study, we proposed an integrated algorithm, ImmuMiRNA, for identifying miRNA modulators of immune-associated pathways. Based on these immune-associated miRNAs, we applied the LASSO algorithm to develop a reliable and individualized signature for evaluating overall survival (OS) and inflammatory landscape of CRC patients. An external public data set and qRT-PCR data from 40 samples were further utilized to validate this signature. As a result, an immune-associated miRNA prognostic signature (IAMIPS) consisting of three miRNAs (miR-194-3P, miR-216a-5p and miR-3677-3p) was established and validated. Patients in the high-risk group possessed worse OS. After stratification for clinical factors, the signature remained a powerful independent predictor for OS. IAMIPS displayed much better accuracy than the traditional clinical stage in assessing the prognosis of CRC. Further analysis revealed that patients in the high-risk group were characterized by inflammatory response, abundance immune cell infiltration, and higher immune checkpoint profiles and tumour mutation burden (TMB). In conclusion, the IAMIPS is highly predictive of OS in patients with CRC, which may serve as a powerful prognostic tool to further optimize immunotherapies for cancer.  相似文献   

4.
Circular RNA (circRNA) is a looped noncoding RNA with a stable structure and tissue-specific expression and widely reported to regulate cancer initiation and progression. However, the circRNA expression patterns and their roles in osteosarcoma initiation and progression are still poorly understood. In this study, we characterized the landscape of circRNAs in osteosarcoma (OS) cell lines, and calculated the epithelial-mesenchymal transition (EMT) scores for OS cell lines. The differential expression analysis revealed that the EMT-related genes were significantly upregulated in the OS cell lines with higher metastatic potentials, and some inflammation-related pathways and pathways involved in cell-cell communications were enriched by these upregulated genes. Furthermore, we constructed a circRNA-based competing endogenous RNA (ceRNA) network, which consisted of 5 circRNAs, 17 miRNAs, and 73 mRNAs. Particularly, hsa_circ_0085360, which had the highest correlation with TRPS1, were characterized by some cancer-related pathways, and TRPS1 and its target gene FGFR3 were closely associated with both event-free survival and overall survival of OS, indicating that hsa_circ_0085360 might have the potential to predict the OS prognosis. In summary, we profiled the circRNA expression patterns in OS, predicted their functionality, and explored the underlying mechanism and prognostic values, which might provide some evidences for OS-related circRNA researches.  相似文献   

5.
利用GEO数据库中的芯片数据,筛选与星形细胞瘤生存预后相关的miRNA-mRNA调控关系对,为后续研究提供理论支持。下载芯片数据利用R语言进行差异表达分析,得到星形细胞瘤较正常组织表达显著改变的miRNA与mRNA;通过miRNA靶基因预测,将靶基因与差异表达mRNA取交集,明确mRNA与miRNA之间的关系;利用GEPIA2.0工具在TCGA数据库中筛选有生存价值的mRNA并验证表达情况,利用OncoLnc工具对相应miRNA进行生存分析。筛选到差异表达的miRNA 90个(表达上调22个,下调68个);差异表达的mRNA 644个(表达下调476个,上调168个);根据miRNA靶基因预测结果,整理出miRNA-mRNA关系对30个,对其中的mRNA与miRNA进行生存分析,共得到7个miRNA-mRNA关系对与LGG患者生存预后明显相关,未筛选到与GBM患者生存预后有关的调控关系对。本研究筛选到的7个miRNA-mRNA调控关系对与LGG患者生存预后显著相关,可为相关研究与治疗提供靶点和参考方向。  相似文献   

6.
7.
BackgroundIncreasing numbers of studies have elucidated the role of competitive endogenous RNA (ceRNA) networks in carcinogenesis. However, the potential role of the paclitaxel-related ceRNA network in the innate mechanism and prognosis of pancreatic cancer has not been identified.MethodsComprehensive bioinformatics analyses were performed to identify drug-related miRNAs (DRmiRNAs), drug-related mRNAs (DRmRNAs) and drug-related lncRNAs (DRlncRNAs) and construct a ceRNA network. The ssGSEA and CIBERSORT algorithms were utilized for immune cell infiltration analysis. Additionally, we validated our paclitaxel-related ceRNA regulatory axis at the gene expression level; functional experiments were conducted to explore the biological functions of the key genes.ResultsA total of 182 mRNAs, 13 miRNAs, and 53 lncRNAs were confirmed in the paclitaxel-related ceRNA network. In total, 6 mRNAs, 4 miRNAs, and 6 lncRNAs were identified to establish a risk signature and exhibited optimal prognostic effects. The mRNA signature can predict the abundance of immune cell infiltration and the sensitivity of different chemotherapeutic drugs and may also have a guiding effect in immune checkpoint therapy. A potential PART1/hsa-mir-21/SCRN1 axis was confirmed according to the ceRNA theory and was verified by qPCR. The results indicated that PART1 knockdown markedly increased hsa-mir-21 expression but inhibited SCRN1 expression, weakening the proliferation and migration abilities.ConclusionsWe hypothesized that the paclitaxel-related ceRNA network strongly influences the innate mechanism, prognosis, and immune infiltration of pancreatic cancer. Our risk signatures can accurately predict survival outcomes and provide a clinical basis.  相似文献   

8.
Previous studies have shown that human papillomavirus (HPV)-negative patients with head and neck squamous cell cancer (HNSCC) suffer from an unsatisfactory prognosis. Long noncoding RNAs (lncRNAs) have been verified to participate in many biological processes, including regulating gene expression as competing endogenous RNAs (ceRNAs), while few studies focused the ceRNA network regulation mechanism in patients with HPV-negative HNSCC tumor. Meanwhile, the immune microenvironment may be critical in the development and prognosis of HPV-negative tumors. Our study aimed to further investigate the pathogenesis and potential biomarkers for the diagnosis, therapy and prognosis of HPV-negative HNSCC through a ceRNA network. Comprehensively analyzing the sequencing data of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in The Cancer Genome Atlas HNSCC dataset, we constructed a differentially expressed ceRNA network containing 131 lncRNAs, 35 miRNAs and 162 mRNAs. Then, survival analysis in the network was cited to explore the prognostic biomarkers. Eight mRNAs, nine lncRNAs, and one miRNA were identified to be associated with prognosis. Neuropilin (NRP) binding function, retinoid X receptor (RXR) binding, and the vascular endothelial growth factor (VEGF) signaling pathway were associated with the enrichment analysis, and they also related to the immune microenvironment. Combined with the analysis of the immune microenvironment differences, we obtained new targeted therapies using an RXR agonist, or a combination of the VEGF monoclonal antibody and an NRP antagonist, which may provide a promising future for HPV-negative HNSCC patients.  相似文献   

9.
The aberrant expression of long noncoding RNAs (lncRNAs) has drawn increasing attention in the field of hepatocellular carcinoma (HCC) biology. In the present study, we obtained the expression profiles of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in 371 HCC tissues and 50 normal tissues from The Cancer Genome Atlas (TCGA) and identified hepatocarcinogenesis-specific differentially expressed genes (DEGs, log fold change ≥ 2, FDR < 0.01), including 753 lncRNAs, 97 miRNAs, and 1,535 mRNAs. Because the specific functions of lncRNAs are closely related to their intracellular localizations and because the cytoplasm is the main location for competitive endogenous RNA (ceRNA) action, we analyzed not only the interactions among these DEGs but also the distributions of lncRNAs (cytoplasmic, nuclear or both). Then, an HCC-associated deregulated ceRNA network consisting of 37 lncRNAs, 10 miRNAs, and 26 mRNAs was constructed after excluding those lncRNAs located only in the nucleus. Survival analysis of this network demonstrated that 15 lncRNAs, 3 miRNAs, and 16 mRNAs were significantly correlated with the overall survival of HCC patients (p < 0.01). Through multivariate Cox regression and lasso analysis, a risk score system based on 13 lncRNAs was constructed, which showed good discrimination and predictive ability for HCC patient survival time. This ceRNA network-construction approach, based on lncRNA distribution, not only narrowed the scope of target lncRNAs but also provided specific candidate molecular biomarkers for evaluating the prognosis of HCC, which will help expand our understanding of the ceRNA mechanisms involved in the early development of HCC.  相似文献   

10.
Lung cancer is one of the deadliest cancers worldwide. To increase the survival rate of lung cancer, it is necessary to explore specific prognosis markers. More and more evidence finds that noncoding RNA is closely associated with the survival of lung cancer, and cancer stem cells (CSCs) also play a significant role in the progress of lung cancer. The objective of this study is to find CSLCs genes that affect the prognosis of lung cancer. The differential expression of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs) in the Cancer Genome Atlas (TCGA) database and differential expression data from microarray of CD326+ and CD326 A549 cell are intersected to identify stable and consistent expression genes (2 lncRNAs, 15 miRNAs, and 134 mRNAs). The intersection of lncRNAs and miRNAs is analyzed by univariate and multivariate Cox regression to obtained prognostic genes. Two miRNAs (miR-30b-5p and miR-29c-3p) are significantly correlated with the overall survival rate. Then using these two miRNAs to construct a risk score model as a prognosis signature of lung cancer. Subsequently, we analyzed the association between two miRNAs and clinical information of lung cancer patients, of which T stage, Neoplasm cancer and risk score (P < .05) can be used as independent prognostic indicators of lung cancer. Finally, target genes of 2 miRNAs and 134 mRNAs were annotated with Gene Ontology and analyzed with Kyoto Encyclopedia of Genes and Genomes pathway, and verified with the GEO database. In summary, this study illustrates the role of miRNAs in the promotion of lung cancer by CSCs, which is important to find molecular biomarkers of lung cancer.  相似文献   

11.
《Genomics》2023,115(3):110622
Previous studies have indicated that exosome-mediated intercellular microRNAs (miRNA) can influence fulminant myocarditis (FM) pathogenesis between immune and cardiac cells. This study explored plasma exosome miRNA profile in pediatric FM using a small RNA microarray. As per our analysis, we observed the differential expression of 266 miRNAs, including 197 upregulated and 69 downregulated candidate genes. Differentially expressed mRNAs in pediatric FM patients' peripheral blood mononuclear cells (PBMCs) were intersected with miRNA target genes predicting tools to screen for FM-specific target genes. The hub genes and their biological and mechanistic pathways related to inflammation and/or the immune system were identified. CeRNA networks of lncRNAs, circRNAs, miRNAs, and mRNAs between cardiomyocytes and PBMCs were finally established. Furthermore, we verified that hsa-miR-146a-5p, hsa-miR-23a-3p, and hsa-miR-27a-3p had higher expression levels in exosomes of pediatric FM patients by qRT-PCR, and hsa-miR-146a-5p shown high sensitivities and specificities for FM diagnosis. Overall, the results demonstrate that the exosome miRNAs play a regulatory role between immune and cardiac cells and provide research targets.  相似文献   

12.
13.
Downregulation of microRNAs (miRNAs) at the 14q32 locus stabilizes the expression of cMYC, thus significantly contributing to osteosarcoma (OS) pathobiology. Here, we show that downregulation of 14q32 miRNAs is epigenetically regulated. The predicted promoter regions of miRNA clusters at 14q32 locus showed no recurrent patterns of differential methylation, but Saos2 cells showed elevated histone deacetylase (HDAC) activity. Treatment with 4-phenylbutyrate increased acetylation of histones associated with 14q32 miRNAs, but interestingly, robust restoration of 14q32 miRNA expression, attenuation of cMYC expression, and induction of apoptosis required concomitant treatment with 5-Azacytidine, an inhibitor of DNA methylation. These events were associated with genome-wide gene expression changes including induction of pro-apoptotic genes and downregulation of cell cycle genes. Comparable effects were achieved in human and canine OS cells using the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat) and the DNA methylation inhibitor Zebularine (Zeb), with significantly more pronounced cytotoxicity in cells whose molecular phenotypes were indicative of aggressive biological behavior. These results suggested that the combination of these chromatin-modifying drugs may be a useful adjuvant in the treatment of rapidly progressive OS.  相似文献   

14.
The role of endothelial cells (ECs) in aortic valve (AV) disease remains relatively unknown; however, disease preferentially occurs in the fibrosa. We hypothesized oscillatory shear (OS) present on the fibrosa stimulates ECs to modify mRNAs and microRNAs (miRNAs) inducing disease. Our goal was to identify mRNAs and miRNAs differentially regulated by OS and laminar shear (LS) in human AVECs (HAVECs) from the fibrosa (fHAVECs) and ventricularis (vHAVECs). HAVECs expressed EC markers as well as some smooth muscle cell markers and functionally aligned with the flow. HAVECs were exposed to OS and LS for 24 h, and total RNA was analyzed by mRNA and miRNA microarrays. We found over 700 and 300 mRNAs down- and upregulated, respectively, by OS; however, there was no side dependency. mRNA microarray results were validated for 26 of 28 tested genes. Ingenuity Pathway Analysis revealed thrombospondin 1 (Thbs1) and NF-κB inhibitor-α (Nfkbia) as highly connected, shear-sensitive genes. miRNA array analysis yielded 30 shear-sensitive miRNAs and 3 side-specific miRNAs. miRNA validation confirmed 4 of 17 shear-sensitive miRNAs and 1 of 3 side-dependent miRNAs. Using miRWalk and several filtering steps, we identified shear-sensitive mRNAs potentially targeted by shear-sensitive miRNAs. These genes and signaling pathways could act as therapeutic targets of AV disease.  相似文献   

15.
16.
Gastric cancer (GC) is a prevalent malignant cancer of digestive system, identification of novel diagnostic and prognostic biomarkers for GC is urgently demanded. The aim of this study was to determine potential long noncoding RNAs (lncRNAs) associated with the pathogenesis and prognosis of GC. Raw noncoding RNA microarray data (GSE53137, GSE70880, and GSE99417) was downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes between GC and adjacent normal gastric tissue samples were screened by an integrated analysis of multiple gene expression profile after gene reannotation and batch normalization. Differentially expressed genes were further confirmed by The Cancer Genome Atlas (TCGA) database. Competing endogenous RNA (ceRNA) network, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway, survival analysis were extensively applied to identify hub lncRNAs and discover potential biomarkers related to diagnosis and prognosis of GC. In total of 246 integrated differential genes including 15 lncRNAs and 241 messenger RNAs (mRNAs) were obtained after intersections of differential genes between GEO and TCGA database. ceRNA network comprised of three lncRNAs (UCA1, HOTTIP, and HMGA1P4), 26 microRNAs (miRNAs) and 72 mRNAs. Functional analysis revealed that three lncRNAs were mainly dominated in cell cycle and cellular senescence. Survival analysis showed that HMGA1P4 was statistically related to the overall survival rate. For the first time, we identified that HMGA1P4, a target of miR-301b/miR-508, is involved in cell cycle and senescence process by regulating CCNA2 in GC. Finally, the expression levels of three lncRNAs were validated to be upregulated in GC tissues. Thus, three lncRNAs including UCA1, HOTTIP, and HMGA1P4 may contribute to GC development and their potential functions might be associated with the prognosis of GC.  相似文献   

17.
Pancreatic cancer is a malignancy of the digestive system characterized by poor prognosis. A number of prognostic messenger RNA (mRNA) signatures have been identified by using the high-throughput expression profiles. MicroRNAs (miRNA) play a critical role in regulating multiple cellular functions. However, no such integrated analysis of miRNAs and mRNAs for studying the prognostic mechanisms of pancreatic cancer has been reported. In this study, we first identified prognostic mRNAs and miRNAs based on The Cancer Genome Atlas datasets, and then performed an enrichment analysis to explore the underlying biological mechanisms involved in pancreatic cancer prognosis at the mRNA level. Furthermore, we performed an integrated analysis of mRNAs and miRNAs to identify prognostic subpathways, which were closely associated with pancreatic cancer genes and tumor hallmarks and involved in hypoxia, oxidative phosphyorylation and xenobiotic metabolisms. Meanwhile, we performed a random walk algorithm based on global network, prognostic mRNAs and miRNAs, and identified top risk mRNAs as the prognostic signature. Finally, an independent testing set was used to confirm the predictive power of the top mRNA signature, and most of these genes involved were known oncogenes. In conclusion, we performed a series of integrated analyses by comprehensively exploring pancreatic cancer prognosis and systematically optimized the prognostic signature for clinical use.  相似文献   

18.
Z Yan  Y Xiong  W Xu  J Gao  Y Cheng  Z Wang  F Chen  G Zheng 《PloS one》2012,7(7):e40037

Background

Gastric cancer (GC) is one of the most common malignancy and primary cause of death in Chinese cancer patients. Recurrence is a major factor leading to treatment failure and low level of 5-year survival rate in GC patients following surgical resection. Therefore, identification of biomarkers with potential in predicting recurrence risk is the key problem of the prognosis in GC patients.

Patients and Methods

A total of 74 GC patients were selected for systematic analysis, consisting of 31 patients with recurrence and 43 patients without recurrence. Firstly, miRNAs microarray and bioinformatics methods were used to characterize differential expressed miRNAs from primary tumor samples. Following, we used a ROC method to select signature with best sensitivity and specificity. Finally, we validated the signature in GC samples (frozen fresh and blood samples) using quantitative PCR.

Results

We have identified 12 differential miRNAs including 7 up-regulated and 5 down-regulated miRNAs in recurrence group. Using ROC method, we further ascertained hsa-miR-335 as a signature to recognize recurrence and non-recurrence cases in the training samples. Moreover, we validated this signature using quantitative PCR method in 64 test samples with consistent result with training set. A high frequency recurrence and poor survival were observed in GC cases with high level of hsa-miR-335 (P<0.001). In addition, we evaluated that hsa-miR-335 were involved in regulating target genes in several oncogenic signal-pathways, such as p53, MAPK, TGF-β, Wnt, ERbB, mTOR, Toll-like receptor and focal adhesion.

Conclusion

Our results indicate that the hsa-miR-335 has the potential to recognize the recurrence risk and relate to the prognosis of GC patients.  相似文献   

19.
Membranous glomerulonephropathy (MGN) is a glomerulopathy characterized by subepithelial deposits of immune complexes on the extracapillary side of the glomerular basement membrane. Insertion of C5b-9 (complement membrane-attack complex) into the membrane leads to functional impairment of the glomerular capillary wall. Knowledge of the molecular pathogenesis of MGN is actually scanty. MicroRNA (miRNA) profiling in MGN and unaffected tissues was performed by TaqMan Low-Density Arrays. Expression of miRNAs and miRNA targets was evaluated in Real-Time polymerase chain reaction (PCR). In vitro transient silencing of miRNAs was achieved through transfection with miRNA inhibitors. Ten miRNAs (let-7a-5p, let-7b-5p, let-7c-5p, let-7d-5p, miR-107, miR-129-3p, miR-423-5p, miR-516-3p, miR-532-3p, and miR-1275) were differentially expressed (DE) in MGN biopsies compared to unaffected controls. Interleukin 6 (IL6) and MYC messenger RNAs (mRNAs; targets of DE miRNAs) were significantly downregulated in biopsies from MGN patients, and upregulated in A498 cells following let-7a-5p or let-7c-5p transient silencing. Gene ontology analysis showed that DE miRNAs regulate pathways associated with MGN pathogenesis, including cell cycle, proliferation, and apoptosis. A significant correlation between DE miRNAs and mRNAs and clinical parameters (i.e., antiphospholipid antibodies, serum creatinine, estimated glomerular filtration, proteinuria, and serum cholesterol) has been detected. Based on our data, we propose that DE miRNAs and their downstream network may be involved in MGN pathogenesis and could be considered as potential diagnostic biomarkers of MGN.  相似文献   

20.
Epithelial ovarian cancer is one of the leading causes of cancer-related death worldwide. Growing evidence indicates that multiple complex altered pathways play important regulatory roles in the development and progression of a variety of cancers, including epithelial ovarian cancer. However, the underlying mechanisms remain unclear. First, we identified differentially expressed messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and microRNAs (miRNAs) in epithelial ovarian cancer by comparing the expression profiles between epithelial ovarian cancer samples and normal tissue samples in different GEO datasets. Then, GO- and KEGG-pathway-enrichment analyses were applied to investigate the primary functions of the overlapped differentially expressed mRNAs. Moreover, the primary enriched genes were used to construct the signal-network with Cytoscape software. In addition, we integrated the relationship among lncRNAs-miRNAs-mRNAs to create a competing endogenous RNA network. Finally, mRNAs that were associated with patient prognosis in epithelial ovarian cancer were selected using univariate Cox regression analysis. A total of 2,225 mRNAs, 336 lncRNAs, and 14 miRNAs were shown to be differentially expressed in epithelial ovarian cancer compared with normal tissues. The dysregulated mRNAs were primarily enriched in cell division and signal transduction, according to Gene Ontology, whereas, according to KEGG, they were primarily enriched in metabolic pathways and pathways in cancer. A total of 10 mRNAs were associated with patient prognosis in ovarian cancer. This study identifies a novel lncRNA–miRNA–mRNA network, which may suggest potential molecular mechanisms underlying the development of epithelial ovarian cancer, providing new insights for survival prediction and interventional strategies for epithelial ovarian cancer.  相似文献   

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