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1.
PurposeWith the increasing incidence of thyroid cancer (TC), the prognostic risk assessment of thyroid cancer has been becoming more and more important. The aim of this study was to screen TC-related biomarkers and identify key multi-long non coding RNA (lncRNA) signature for prognostic risk assessment of papillary TC.Material and methodsThe lncRNAs differentially expressed between TC tissue and adjacent normal tissue was identified by R language. Bioinformatics analysis was applied to screen the lncRNAs significantly associated with prognosis in TC patients and build the multi-lncRNA signature. The lncRNAs were annotated by co-expression and enrichment analysis to demonstrate the underlying mechanism of their effect on prognosis.Results285 up-regulated and 174 down-regulated differently expressed lncRNAs were identified. Based on seven signature lncRNAs (AL591846.2, AC253536.3, AC004112.1, LINC00900, AC008555.1, TNRC6C-AS1, LINC01736) a prognostic risk assessment model was built. The model can segregate the patients into the high-risk and low-risk groups (P value <0.0001, CI: 0.02~0.14). ROC analysis revealed that the area under the curve reached 0.86, indicating that this model had an excellent sensitivity and specificity. Also, the model could act as an independent prognostic indication (HR ?= ?2.90, P value ?= ?0.0094 with multivariate analysis). Annotation results further supported and enriched our understanding of the seven signature lncRNAs. Importantly, expression levels of three of the seven lncRNAs were confirmed in Gene Expression Omnibus (GEO) data.ConclusionsThis study has provided a promising method for the prognostic risk assessment in patients with TC.  相似文献   

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Colorectal cancer (CRC), one of the common malignant cancers in the world, is caused by accumulated alterations of genetic and epigenetic factors over a long period of time. Along with that protein‐coding genes being identified as oncogenes or tumor suppressors in CRC, a number of lncRNAs have also been found to be associated with CRC. Considering the important regulatory role of lncRNAs, the first goal of this study was to identify CRC‐associated lncRNAs from a public database. One such lncRNA, LINC00472, was verified to be downregulated in CRC cell lines and cancer tissues compared with adjacent tissues. In addition, the down‐regulation of LINC00472 seemed to be caused by DNA hypermethylation at its promoter region. Furthermore, the expression of LINC00472 and DNA methylation of promoter were significantly correlated with clinicopathological features. And DNA hypermethylation of LINC00472 may serve as a better diagnostic biomarker than its expression for CRC. Finally, we predicted the functions of LINC00472 and constructed a regulatory network and found LINC00472 may be involved in cell cycle and cell proliferation processes. Our results may provide a clue to further research into the function and regulatory mechanism of LINC00472 in CRC.  相似文献   

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The COL9A3 gene encodes one of the three alpha chains of Type IX collagen, with heterozygous variants reported to cause multiple epiphyseal dysplasia, and suggested as contributory in some cases of sensorineural hearing loss. Patients with homozygous variants have midface hypoplasia, myopia, sensorineural hearing loss, epiphyseal changes and carry a diagnosis of Stickler syndrome. Variants in COL9A3 have not previously been reported to cause vitreoretinal degeneration and/or retinal detachments. This report describes two families with autosomal dominant inheritance and predominant features of peripheral vitreoretinal lattice degeneration and retinal detachment. Genomic sequencing revealed a heterozygous splice variant in COL9A3 [NG_016353.1(NM_001853.4):c.1107 + 1G>C, NC_000020.10(NM_001853.4):c.1107 + 1G>C, LRG1253t1] in Family 1, and a heterozygous missense variant [NG_016353.1(NM_001853.4):c.388G>A p.(Gly130Ser)] in Family 2, each segregating with disease. cDNA studies of the splice variant demonstrated an in-frame deletion in the COL2 domain, and the missense variant occurred in the COL3 domain, both indicating the critical role of Type IX collagen in the vitreous base of the eye.Subject terms: Genetic testing, Medical genetics, Medical genomics  相似文献   

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There is an increased pressure to return results from research studies. In Iceland, deCODE Genetics has emphasised the importance of returning results to research participants, particularly the founder pathogenic BRCA2 variant; NM_000059.3:c.771_775del. To do so, they opened the website www.arfgerd.is. Individuals who received positive results via the website were offered genetic counselling (GC) at Landspitali in Reykjavik. At the end of May 2019, over 46.000 (19% of adults of Icelandic origin) had registered at the website and 352 (0.77%) received text message informing them about their positive results. Of those, 195 (55%) contacted the GC unit. Additionally, 129 relatives asked for GC and confirmatory testing, a total of 324 individuals. Various information such as gender and age, prior knowledge of the variant and perceived emotional impact, was collected. Of the BRCA2 positive individuals from the website, 74 (38%) had prior knowledge of the pathogenic variant (PV) in the family. The majority initially stated worries, anxiety or other negative emotion but later in the process many communicated gratitude for the knowledge gained. Males represented 41% of counsellees as opposed to less than 30% in the regular hereditary breast and ovarian (HBOC) clinic. It appears that counselling in clinical settings was more reassuring for worried counsellees. In this article, we describe one-year experience of the GC service to those who received positive results via the website. This experience offers a unique opportunity to study the public response of a successful method of the return of genetic results from research.Subject terms: Health care, Social sciences  相似文献   

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The aim of this study was to explore colorectal tumor-associated macrophage (TAM) biomarkers for early diagnosis and surveillance of colorectal cancer (CRC). We used bioinformatic methods to screen array expression data of CRC-related macrophages (GEO: GSE29214) to detect the differentially expressed genes (DEGs) between CRC-related macrophages and normal control cells. We found 431 DEGs in TAMs compared with the control group; 399 were up-regulated and 32 were down-regulated. A functional enrichment analysis showed that the DEGs were involved in positive regulation of the ERK1 and ERK2 cascade, cell activation involved in the immune response, cytokine-mediated signaling pathway, and receptor activity, all of which were significantly enriched. We constructed a protein-protein interaction (PPI) network to identify hub genes. We identified 10 hub genes: ITGB2, ITGAM, C3AR1, PTAFR, C3, CYBB, FCER1G, PLAU, STOM, and GPR84, in the PPI network. We verified the results using array expression data of peripheral blood mononuclear cells (GEO: GSE47756). The results showed that the expression trends of CYBB, PLAU, and STOM were consistent with those found in the GSE29214 dataset. Further verification with The Cancer Genome Atlas and Human Protein Atlas showed that the high expression of PLAU in TAMs was statistically significant (P<0.05). We concluded that PLAU may be a biomarker of CRC-associated macrophages and may have prognostic and predictive significance for clinical utility in CRC management.  相似文献   

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Background: Dysregulation of long non-coding RNAs (lncRNAs) plays critical roles in tumor progression. The purpose of this study was to investigate the relationship between lncRNA CCAT2 expression and cervical squamous cell cancer susceptibility and prognosis. Methods: Expression levels of lncRNA CCAT2 in 123 cervical squamous cell tumor specimens were determined by quantitative real-time PCR (qRT-PCR), to clarify the clinical significance of lncRNA CCAT2 in cervical squamous cell cancer, we further discussed the relationship between lncRNA CCAT2 expression and overall survival (OS) and progression-free survival (PFS). Results: In the present study, we found that lncRNA CCAT2 was up-regulated in cervical squamous cell cancer tissues compared to the adjacent non-tumor tissues. In addition, the high lncRNA CCAT2 expression was significantly associated with the FIGO stage, lymph node metastasis and depth of cervical invasion (P<0.05). Furthermore, patients with high expression of lncRNA CCAT2 had poor OS (HR=2.813, 95% CI: 1.504-6.172; P=0.017), and PFS rates (HR=3.072, 95% CI: 1.716-8.174; P=0.008). Multivariate Cox proportional hazard model analysis demonstrated that high lncRNA CCAT2 expression was an independent poor prognostic factor for cervical squamous cell cancer patients. Conclusions: Our study suggested that high expression of lncRNA CCAT2 is related to the prognosis of cervical squamous cell cancer; it may be a new prognostic biomarker and potential therapeutic target for cervical squamous cell cancer intervention.  相似文献   

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Congenital autosomal recessive cataract with unknown genetic etiology is one of the most common Mendelian diseases among the Turkic-speaking Yakut population (Eastern Siberia, Russia). To identify the genetic cause of congenital cataract spread in this population, we performed whole-exome sequencing (Illumina NextSeq 500) in one Yakut family with three affected siblings whose parents had preserved vision. We have revealed the novel homozygous c.1621C>T transition leading to premature stop codon p.(Gln541*) in exon 8 of the FYCO1 gene (NM_024513.4). Subsequent screening of c.1621C>T p.(Gln541*) revealed this variant in a homozygous state in 25 out of 29 Yakut families with congenital cataract (86%). Among 424 healthy individuals from seven populations of Eastern Siberia (Russians, Yakuts, Evenks, Evens, Dolgans, Chukchi, and Yukaghirs), the highest carrier frequency of c.1621C>T p.(Gln541*) was found in the Yakut population (7.9%). DNA samples of 25 homozygous for c.1621C>T p.(Gln541*) patients with congenital cataract and 114 unaffected unrelated individuals without this variant were used for a haplotype analysis based on the genotyping of six STR markers (D3S3512, D3S3685, D3S3582, D3S3561, D3S1289, and D3S3698). The structure of the identified haplotypes indicates a common origin for all of the studied mutant chromosomes bearing c.1621C>T p.(Gln541*). The age of the с.1621C>T p.(Gln541*) founder haplotype was estimated to be approximately 260 ± 65 years (10 generations). These findings characterize Eastern Siberia as the region of the world with the most extensive accumulation of the unique variant c.1621C>T p.(Gln541*) in the FYCO1 gene as a result of the founder effect.Subject terms: Visual system, Genetics research, Clinical genetics  相似文献   

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Recently, more and more studies show that long non-coding RNAs (lncRNAs) play a very important role in various biological processes. However, research on lncRNA in the tumor cell drug resistance of it is seldom reported. In this study, gemcitabine-resistant pancreatic cancer cell line SWl990/GZ was obtained by treating parental cell line SWl990 in vitro with increasing dosage of gemcitabine in culture medium intermittently for ten months. We identified4983 of 13310 detected lncRNAs demonstrated > 2-fold abnormally expressed in response to the gemcitabine-resistant, among of them, 1993 and 2990 lncRNAs were upregulated and downregulated. Meanwhile, 4759 mRNAs exhibited at least a 2-fold, of these, 2671 and 2088 mRNAs were upregulated and downregulated. Gene Ontology analysis and Pathway analysis revealed that differential expression mRNA involved in significant biological regulatory function and some genes may be particular to pancreatic cancer chemotherapy resistance. Quantitative real time PCR confirmed the changes of six lncRNAs (RP11-58D2.1, lincRNA-ZNF532, AP000221.1, CTC-338M12.5, CR619813, DDX6P) and nine mRNAs (SYT1, FAM171B, ZNF331, FAM187B, CYP1A1, SRXN1, HIST1H2BL, TOMM40L and SPP1) in SW1990 and SW1990/GZ. We also found that the upregulating of gemcitabine on the expression of lincRNA-ZNF532 was time-dependent. Gemcitabine at a range from 1.0 μM to 16.0 μM induced a increase of lincRNA-ZNF532 in SW1990 cells. The relative level of DDX6P is opposite to that of lincRNA-ZNF53 in the same circumstance. In conclusion, the dysregulated lncRNAs and mRNAs identified in this work may represent good candidates for future diagnostic or prognostic biomarkers and therapeutic targets.  相似文献   

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Introduction: Long non-coding RNAs (lncRNAs) have been demonstrated to play key roles in tumorgenesis, and the lncRNA LET is down-regulated in several cancers. However, little is known about the function of lncRNA LET in human cervical cancer. The aim of this study was to investigate the clinical significance of lncRNA LET expression in cervical cancer. Methods: We examined the expression of lncRNA LET in 94 cervical cancer tissues and matched adjacent non-tumor tissues using quantitative real-time PCR and analyzed its correlation with the clinicopathological features. Results: The results showed that lncRNA LET expression in cervical cancer tissues was significantly down-regulated compared with the adjacent non-tumor tissues (P < 0.05). Decreased lncRNA LET expression was significantly correlated with FIGO stage, lymph node metastasis, and depth of cervical invasion (P < 0.05), but not other clinical characteristics. Moreover, cervical cancer patients with lncRNA LET lower expression have shown significantly poorer overall survival than those with higher lncRNA LET expression (P < 0.05). Univariate and multivariate analyses suggested that lncRNA LET expression served as an independent predictor for overall survival. Conclusions: Our data provided the first evidence that lncRNA LET may represent a prognostic marker and a potential therapeutic target for cervical cancer.  相似文献   

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Background

Glioblastoma multiform (GBM) is a devastating brain tumor with maximum surgical resection, radiotherapy plus concomitant and adjuvant temozolomide (TMZ) as the standard treatment. Diverse clinicopathological and molecular features are major obstacles to accurate predict survival and evaluate the efficacy of chemotherapy or radiotherapy. Reliable prognostic biomarkers are urgently needed for postoperative GBM patients.

Methods

The protein coding genes (PCGs) and long non-coding RNA (lncRNA) gene expression profiles of 233 GBM postoperative patients were obtained from The Cancer Genome Atlas (TCGA), TANRIC and Gene Expression Omnibus (GEO) database. We randomly divided the TCGA set into a training (n?=?76) and a test set (n?=?77) and used GSE7696 (n?=?80) as an independent validation set. Survival analysis and the random survival forest algorithm were performed to screen survival associated signature.

Results

Six PCGs (EIF2AK3, EPRS, GALE, GUCY2C, MTHFD2, RNF212) and five lncRNAs (CTD-2140B24.6, LINC02015, AC068888.1, CERNA1, LINC00618) were screened out by a risk score model and formed a PCG-lncRNA signature for its predictive power was strongest (AUC?=?0.78 in the training dataset). The PCG-lncRNA signature could divide patients into high- risk or low-risk group with significantly different survival (median 7.47 vs. 18.27 months, log-rank test P?<?0.001) in the training dataset. Similar result was observed in the test dataset (median 11.40 vs. 16.80 months, log-rank test P?=?0.001) and the independent set (median 8.93 vs. 16.22 months, log-rank test P?=?0.007). Multivariable Cox regression analysis verified that it was an independent prognostic factor for the postsurgical patients with GBM. Compared with IDH mutation status, O-(6)-methylguanine DNA methyltransferase promoter methylation status and age, the signature was proved to have a superior predictive power. And stratified analysis found that the signature could further separated postoperative GBM patients who received TMZ-chemoradiation into high- and low-risk groups in TCGA and GEO dataset.

Conclusions

The PCG-lncRNA signature was a novel prognostic marker to predict survival and TMZ-chemoradiation response in GBM patients after surgery.
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IntroductionHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Despite the therapeutic advances in HCC in the past few decades, the mortality rate of HCC is still high. Hepatitis C (HCV) infection is one of the major etiological risk factors of HCCs. However, the underlying mechanisms of HCV-induced hepatocarcinogenesis remain largely unclear.Material and methodsOur study represented the comprehensive analysis of differentially expressed lncRNAs in HCV-positive HCC for the first time by analyzing the public dataset GSE17856. Co-expression network and gene ontology (GO) analysis revealed the functions of those differentially expressed lncRNAs.ResultsWe identified 256 upregulated lncRNAs and 198 downregulated lncRNAs in HCV- positive HCC compared to the normal liver tissues. Co-expression network and GO analysis showed that these lncRNAs were involved in regulating metabolism, energy pathways, proliferation and the immune response. Seven lncRNAs (LOC341056, CCT6P1, PTTG3P, LOC643387, LOC100133920, C3P1 and C22orf45) were identified as key lncRNAs and co-expressed with more than 100 differentially expressed genes (DEGs) in HCV-related HCC. Kaplan-Meier analysis showed that higher expression levels of LOC643387, PTTG3P, LOC341056, CCT6P1 and lower expression levels of C3P1 and C22orf45 were associated with shorter survival time in the TCGA dataset.ConclusionsWe believe that this study can provide novel potential therapeutic and prognostic biomarkers for HCV-positive HCC.  相似文献   

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Background: In recent years, LncRNA acts as a member of competing endogenous RNA (ceRNA), playing an important role in drug resistance of lung cancer. The aim of this study was to identify potential biomarkers about cisplatin resistant lung cancer cells using a comprehensive ceRNA network.Methods: GSE6410 (GPL-201) analyzed gene expression changes about cisplatin resistance in A549 NSCLC cells. GSE43249 (GPL-14613) included noncoding RNA expression profiling derived from the cisplatin resistant A549 lung cells. GEO2R, an online analysis tool, analyzed the differentially expressed mRNAs and miRNAs (DEmRNAs and DEmiRNAs). To explore the functional enrichment implication of differentially expressed mRNAs, we used the GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis. Through miRDB, Targetscan, Starbase and miRWalk, we found targeted miRNAs. The Kaplan-Meier curve method was used to show clinical survival analysis of targeted RNAs (P<0.05). The Starbase database predicted potential lncRNAs mediated targeted miRNAs. Eventually, the novel ceRNA network of lncRNAs, miRNAs, mRNA was constructed by cytoscape3.7.2.Results: 118 differentially expressed mRNAs were the basis of the mediated ceRNA network. DAVID and Kaplan-Meier picked out BAX, an apoptosis regulator. Venn diagram demonstrated 8 miRNAs commonly regulating BAX. Starbase predicted lncRNA XIST mediated miRNAs. Finally, lncRNA XIST may be a useful biomarker regulating cisplatin resistance in lung cancer cells and further, we explored the BAX may effect tumor-infiltrating immune cells.Conclusions: LncRNA XIST competitively bound to miRNA 520 in the regulation of cisplatin resistance by BAX, participating apoptosis in the p53 signaling pathway.  相似文献   

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Background: Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA Sox2ot is up-regulated in some tumors. However, the contributions of Sox2ot to hepatocellular carcinoma (HCC) remain largely unknown. Methods: In the present study, expression of lncRNA Sox2ot was evaluated by quantitative real-time PCR in tumor tissues and adjacent non-tumor tissues in 84 HCC patients. The association of lncRNA Sox2ot expression with clinicopathological features and the prognosis of HCC patients were also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox’s proportional hazards model. Small interfering RNA assay was used to explore the function of lncRNA Sox2ot on HCC cell migration and invasion. Results: lncRNA Sox2ot expression level was significantly higher in HCC tissues compared with adjacent non-tumor tissues (P<0.05). High expression of lncRNA Sox2ot was associated with histological grade, TNM stage, and vein invasion. The 5-year overall survival of high lncRNA Sox2ot expression group was significantly shorter than that of low lncRNA Sox2ot expression group (P<0.05). The multivariate Cox regression analysis indicated that lncRNA Sox2ot expression was an independent prognostic factor for overall survival. In addition, the metastasis ability of HCC cells was significantly decreased by knocking down lncRNA Sox2ot expression. Conclusions: The results suggested that lncRNA Sox2ot played crucial roles in promoting HCC cell migration and invasion, and might represent a novel prognostic biomarker for HCC.  相似文献   

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Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumor formation and development. Small nucleolar RNA host gene 6 (SNHG6) is a recently identified cancer-related lncRNA, and its role in colorectal cancer (CRC) remains to be explored. The aim of this study was to evaluate the expression and function of SNHG6 in CRC. The expression of SNHG6 was detected by real time quantitative RT-PCR (qRT-PCR) in 74 CRC tissues and matched noncancerous tissues (NCTs). Relationships between the expression levels of SNHG6 and various clinicopathological features were analyzed by Chi-square test. The Kaplan-Meier method and log-rank test were applied to compare the survival distribution between different groups. CCK8 assay and colony formation assay were used to measure the effect of SNGH6 on cell proliferation. Flow cytometric analysis was performed to measure the effect of SNHG6 on cell cycle and apoptosis. Our results showed that SNHG6 was up-regulated more than 1.5-fold in 50.0% (37/74) of CRC tissues compared with paired NCTs (P?<?0.0001). High level of SNHG6 expression was strongly associated with advanced tumor stage (P?=?0.026) and predicted poor prognosis of CRC (P?=?0.0215). The Cox proportional hazards model demonstrated that SNHG6 expression was an independent prognostic factor for CRC (HR, 2.568; 95% CI, 1.055–6.252; P?=?0.038). Furthermore, SNHG6 knockdown by siRNA could inhibit cell proliferation, cell cycle progression, and induce apoptosis. Taken together, SNHG6 functions as an oncogene in CRC and appears as a novel prognositic factor for CRC patients.  相似文献   

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Despite advances made in the diagnosis and treatment of human colorectal cancer (CRC), the long-term survival for CRC remains poor. Long non-coding RNA anti-differentiation ncRNA (lncRNA DANCR) was identified to be involved in carcinogenesis of hepatocellular carcinoma. While its expression in CRC and potential role in tumor progression is still unknown. In the present study, we investigated the expression level of lncRNA DANCR as well as its association with CRC progression and prognosis. The expression of lncRNA DANCR was detected by quantitative real-time PCR (qRT-PCR) in 104 CRC specimens. The prognostic value of lncRNA DANCR was further analysis. Our results showed that lncRNA DANCR expression was increased in CRC tissues compared with that in adjacent normal tissues (P<0.05). In addition, tumors with high lncRNA DANCR expression was correlated with TNM stage, histologic grade, and lymph node metastasis (P<0.05). Kaplan-Meier analysis showed that patients with high lncRNA DANCR expression had a shorter overall survival (OS) and disease-free survival (DFS) compared with the low lncRNA DANCR expression group (P<0.05). Moreover, in a multivariate Cox model, our results showed that lncRNA DANCR expression was an independent poor prognostic factor for both OS and DFS in CRC. Our data indicated that lncRNA DANCR expression might be a novel potential biomarker for CRC prognosis.  相似文献   

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