scholarly journals Bioinformatic analysis and identification of potential prognostic microRNAs and mRNAs in thyroid cancer

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4674 ◽  
Author(s):  
Jianing Tang ◽  
Deguang Kong ◽  
Qiuxia Cui ◽  
Kun Wang ◽  
Dan Zhang ◽  
...  

Thyroid cancer is one of the most common endocrine malignancies. Multiple evidences revealed that a large number of microRNAs and mRNAs were abnormally expressed in thyroid cancer tissues. These microRNAs and mRNAs play important roles in tumorigenesis. In the present study, we identified 72 microRNAs and 1,766 mRNAs differentially expressed between thyroid cancer tissues and normal thyroid tissues and evaluated their prognostic values using Kaplan-Meier survival curves by log-rank test. Seven microRNAs (miR-146b, miR-184, miR-767, miR-6730, miR-6860, miR-196a-2 and miR-509-3) were associated with the overall survival. Among them, three microRNAs were linked with six differentially expressed mRNAs (miR-767 was predicted to target COL10A1, PLAG1 and PPP1R1C; miR-146b was predicted to target MMP16; miR-196a-2 was predicted to target SYT9). To identify the key genes in the protein-protein interaction network , we screened out the top 10 hub genes (NPY, NMU, KNG1, LPAR5, CCR3, SST, PPY, GABBR2, ADCY8 and SAA1) with higher degrees. Only LPAR5 was associated with the overall survival. Multivariate analysis demonstrated that miR-184, miR-146b, miR-509-3 and LPAR5 were an independent risk factors for prognosis. Our results of the present study identified a series of prognostic microRNAs and mRNAs that have the potential to be the targets for treatment of thyroid cancer.

2020 ◽  
Author(s):  
Tong Li ◽  
Qiaofei Liu ◽  
Ronghua Zhang ◽  
Quan Liao ◽  
Yupei Zhao

Abstract Background: As one of the most lethal cancers, pancreatic cancer has been characterized by abundant supportive tumor-stromal cell microenvironment. Although the advent of tumor-targeted immune checkpoint blockers has brought light to patients with other cancers, its clinical efficacy in pancreatic cancer has been greatly limited due to the protective stroma . Thus, it is urgent to find potential new targets and establish multi-regulatory networks to predict patient prognosis andimprove treatment. Methods: We followed a strategy based on mining the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm to obtain the immune scores and stromal scores. Differentially expressed genes (DEGs) associated with poor overall survival of pancreatic cancer were screened from a TCGA cohort. By comparing global gene expression with high vs. low immune scores and subsequent Kaplan-Meier analysis, DEGs that significantly correlate with poor overall survival of pancreatic cancer in TCGA cohort were extracted. After constructing the protein-protein interaction network using STRING and limiting the genes within the above DEGs, we utilized RAID 2.0, TRRUST v2 database and degree and betweenness analysis to obtain non-coding RNA (ncRNA)-pivotal nodes and TF-pivotal nodes. Finally, multi-regulatory networks have been constructed and pivotal drugs with potential benefit for pancreatic cancer patients were obtained by screening in the DrugBank. Results: In this study, we obtained 246 DEGs that significantly correlate with poor overall survival of pancreatic cancer in the TCGA cohort. With the advent of 38 ncRNA-pivotal nodes and 7 TF-pivotal nodes, the multi-factor regulatory networks were constructed based on the above pivotal nodes. Prognosis-related genes and factors such as HCAR3, PPY, RFWD2, WSPAR and Amcinonide were screened and investigated. Conclusion: The multi-regulatory networks constructed in this study are not only beneficial to improve treatment and evaluate patient prognosis with pancreatic cancer, but also favorable for implementing early diagnosis and personalized treatment. It is suggested that these factors may play an essential role in the progression of pancreatic cancer.


2020 ◽  
Author(s):  
Shuangqing Cao ◽  
Lei Zheng

Abstract Background: MicroRNA-195 (miR-195), a tumor suppressor, had reported to be involved in carcinogenesis and the progression of some cancers. However, the prognostic value of miR-195 in cervical cancer remained unclear. The purpose of this study was to detect the expression of miR-195 in cervical cancer tissues and to investigate its correlation with tumor progression and prognosis.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of miR-195 in cervical cancer tissues and corresponding adjacent normal tissues. The relationship between miR-195 expression and clinical characteristics of patients was analyzed by chi-square test. Kaplan-Meier method was applied to compare the overall survival, and the prognostic value of miR-195 was estimated via cox regression analysis.Results: Compared with normal tissues, miR-195 expression was significantly down-regulated in cervical cancer tissues (P < 0.001). Importantly, decreased expression of miR-195 was closely associated with FIGO stage, lymph node metastasis and vascular invasion (P < 0.05). Additionally, Kaplan-Meier analysis indicated that patients with high miR-195 expression had obviously longer overall survival than those with low miR-195 expression (log rank test, P = 0.001). And miR-195 was an independent prognostic factor of cervical cancer patients via univariate and multivariate cox regression analyses.Conclusions: Decreased expression of miR-195 is associated with the progression of cervical cancer. And miR-195 may have potency to predict the prognosis of cervical cancer.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yan Tang ◽  
Chunsheng Hu

Lung adenocarcinoma (LUAD) is the most prevalent histologic type of lung cancer, associated with a high incidence rate and substantial mortality rate worldwide. Accumulating evidence shows that the aberrant expression of neuromedin U (NMU) contributes to the initiation and progression of cancer. Herein, we explored whether NMU could be adopted as a new diagnostic and therapeutic marker in LUAD. The UALCAN and GEPIA web resources were employed to assess data on the NMU expression in LUAD. The STRING web resource was used to develop the PPI (protein-protein interaction) network of NMU, whereas Cytoscape was applied for module analysis. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of NMU and the interacting proteins were examined using the WebGestalt tool. Survival analysis was performed with the Kaplan-Meier plotter tool. Results revealed that the NMU expression in LUAD was significantly higher than in the nonmalignant tissues. Moreover, higher NMU levels were dramatically related to shorter overall survival, first progression survival, and postprogression survival. The specific gene mutations G45V, R143T, and F152L of NMU occurred in LUAD samples and were associated with a worse prognosis in patients. KEGG and western blot analyses demonstrated an association of NMU with the cell cycle and the cAMP signaling cascade. Bioinformatic analysis and the in vitro experiments implicated NMU as a promising prognostic signature and treatment target for LUAD.


2020 ◽  
Author(s):  
Jin Lan ◽  
Jingzhan Huang ◽  
Yuan Gao ◽  
Jingbo Sun ◽  
Longshan Zhang ◽  
...  

Abstract Background: TRIP13 is a member belonging to a large AAA+ ATPases protein super family. Emerging evidences had shown that TRIP13 may serve as an oncogene However, the function of TRIP13 in BC has not yet been elucidated. Methods: By utilizing the multiple database across BC, we presented the expression of TRIP13 in BC tissue and normal control. We then verified the expression of TRIP13 in patients with BC by immunohistochemical (IHC) staining. Kaplan-Meier plots were used to perform the survival analysis. Further, gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and PPI (protein-protein interaction) network were performed to explore the biological function and potential regular pathway of TRIP13 in BC. Results: The multiple database and immunohistochemical (IHC) showed that higher TRIP13 expression in BC tissue compared to normal tissue. TRIP13 was highly exprssed in lung metastasis lesion compared with primary tumor in our BALB/C mice 4T1 BC models. Kaplan-Meier plots also revealed that high TRIP13 expression correlated to poor survival in patients with BC. Moreover, GSEA analysis revealed that TRIP13 was primarily enriched in the processes of cell division and proliferation. Finally 10 hub genes with a high score of connectivity were filtered from the PPI network, including MAD2L1, CDC20, CDC5L, CDK1, CCNA2, BUB1B, RAD51, SPO11, KIF11 and AURKB. Conclusion: High TRIP13 expression predicted poor prognosis and contributed tumor growth and metastasis in the BC. Thus, ARL3 may be a prognostic marker and therapeutic target for glioma. TRIP13 may be a favorable biomarker and effective therapeutic target for BC. Keywords: TRIP13; breast cancer; metastasis; bioinformatic analysis, prognosis


2021 ◽  
Vol 15 (8) ◽  
pp. 927-936 ◽  
Author(s):  
Yan Peng ◽  
Yuewu Liu ◽  
Xinbo Chen

Background: Drought is one of the most damaging and widespread abiotic stresses that can severely limit the rice production. MicroRNAs (miRNAs) act as a promising tool for improving the drought tolerance of rice and have become a hot spot in recent years. Objective: In order to further extend the understanding of miRNAs, the functions of miRNAs in rice under drought stress are analyzed by bioinformatics. Method: In this study, we integrated miRNAs and genes transcriptome data of rice under the drought stress. Some bioinformatics methods were used to reveal the functions of miRNAs in rice under drought stress. These methods included target genes identification, differentially expressed miRNAs screening, enrichment analysis of DEGs, network constructions for miRNA-target and target-target proteins interaction. Results: (1) A total of 229 miRNAs with differential expression in rice under the drought stress, corresponding to 73 rice miRNAs families, were identified. (2) 1035 differentially expressed genes (DEGs) were identified, which included 357 up-regulated genes, 542 down-regulated genes and 136 up/down-regulated genes. (3) The network of regulatory relationships between 73 rice miRNAs families and 1035 DEGs was constructed. (4) 25 UP_KEYWORDS terms of DEGs, 125 GO terms and 7 pathways were obtained. (5) The protein-protein interaction network of 1035 DEGs was constructed. Conclusion: (1) MiRNA-regulated targets in rice might mainly involve in a series of basic biological processes and pathways under drought conditions. (2) MiRNAs in rice might play critical roles in Lignin degradation and ABA biosynthesis. (3) MiRNAs in rice might play an important role in drought signal perceiving and transduction.


2021 ◽  
pp. 000313482199506
Author(s):  
Youngbae Jeon ◽  
Kyoung-Won Han ◽  
Won-Suk Lee ◽  
Jeong-Heum Baek

Purpose This study is aimed to evaluate the clinical outcomes of surgical treatment for nonagenarian patients with colorectal cancer. Methods This retrospective single-center study included patients diagnosed with colorectal cancer at the age of ≥90 years between 2004 and 2018. Patient demographics were compared between the operation and nonoperation groups (NOG). Perioperative outcomes, histopathological outcomes, and postoperative complications were evaluated. Overall survival was analyzed using Kaplan-Meier methods and log-rank test. Results A total of 31 patients were included (16 men and 15 women), and the median age was 91 (range: 90‐96) years. The number of patients who underwent surgery and who received nonoperative management was 20 and 11, respectively. No statistical differences in baseline demographics were observed between both groups. None of these patients were treated with perioperative chemotherapy or radiotherapy. Surgery comprised 18 (90.0%) colectomies and 2 (10.0%) transanal excisions. Short-term (≤30 days) and long-term (31‐90 days) postoperative complications occurred in 7 (35.0%) and 4 (20.0%) patients, respectively. No complications needed reoperation, such as anastomosis leakage or bleeding. No postoperative mortality occurred within 30 days: 90-day postoperative mortality occurred in two patients (10.0%), respectively. The median overall survival of the operation group was 31.6 (95% confidence interval: 26.7‐36.5) and that of NOG was 12.5 months (95% CI: 2.4‐22.6) ( P = 0.012). Conclusion Surgical treatment can be considered in carefully selected nonagenarian patients with colorectal cancer in terms of acceptable postoperative morbidity, with better overall survival than the nonsurgical treatment.


2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-22
Author(s):  
Allison Taylor ◽  
Kimberley Doucette ◽  
Bryan Chan ◽  
Xiaoyang Ma ◽  
Jaeil Ahn ◽  
...  

Introduction The literature suggests a widespread reduction in the availability and accessibility of newer treatment options among marginalized groups in AML. Studies from large national databases point to lower socio-economic status, Hispanic and African American race, Medicare or no insurance, being unmarried, treatment at non-academic centers, and rural residence as negatively impacting overall survival (OS) and rates of chemotherapy utilization in AML patients (Patel et al. 2015, Jaco et al. 2017, Bhatt et al. 2018, Master et al. 2016). We hypothesized that facility affiliation and pt volume would also have important effects on time to treatment (TTT) and OS in AML, even when these socioeconomic disparities were accounted for. Methods For this retrospective analysis, we used NCDB data that included 124,988 pts over the age of 18 with AML between the years 2004-2016. Variables analyzed included facility types described as community cancer programs (CP), comprehensive community cancer programs (CCP), academic/research center cancer programs (AC) and integrated network cancer programs (IN), and volume of facilities defined as high volume (HV) and low volume (LV). HV facilities had case volumes of ≥ 99th percentile and all other facilities were classified as LV. Multivariate analyses (MVA) included demographic and socioeconomic covariables. We used Cox proportional hazard analysis for both TTT and OS MVA. The Kaplan-Meier method was used to estimate median TTT and OS, and the log rank test used to compare TTT and OS across predictor variables. Results The median age of AML patients was 63 yrs (range 18-90) with 54% males, and 86% Caucasian. Five percent of patients were treated at CP, 30% at CCP, 44% at AC, and 10% at IN. 21% at HV facilities and 79% at LV facilities. Median TTT in days at CP facilities was 7, compared to 5 days in CCP and AC facilities versus 4 days at IN (p&lt;0.0001). TTT was 5 days at HV facilities versus 4 days at LV facilities (p&lt;0.0001). Kaplan-Meier curves showed that TTT was similar between HV and LV facilities(figure 1). The median OS was 3.25 months in CP compared to 4.34 months at CCP, 5.06 months at IN and 9.53 months at AC (p&lt;0.0001). For facility volume, the median OS was 13.11 months in HV facilities compared to 6.93 months in LV facilities (p&lt;0.0001). When sex, race, age, Hispanic Origin, education, urban/rural residence, Charlson-Deyo Comorbidity score and Great Circle Distance were adjusted for in MVA (table 1), the OS was higher in AC versus CP facilities (hazard ratio [HR] of 0.90 (0.87-0.93, p&lt;0.0001), and there was no statistically significant difference with comparison of other facility types to CP. Similarly, there was a lower OS at LV versus HV facilities with a HR of 1.14 (1.12-1.16, p&lt;0.0001). CCP facilities had a shorter TTT compared to CP with a HR of 1.21 (1.17-1.26, p&lt;0.0001). AC had a shorter TTT than CP with a HR of 1.17 (1.13-1.22, p&lt;0.0001), and IN had a shorter TTT compared to CP with a HR of 1.29 (1.24-1.34, p&lt;0.0001). Additionally, TTT in the MVA for facility volume was shorter in LV facilities compared to HV facilities with HR of 1.05 (1.04-1.07, p&lt;0.0001) [table 1]. Conclusion When adjusting for various socioeconomic factors, we found that TTT was longest in CP compared to CCP, AC, and IN. Treatment at a LV facility resulted in a decreased overall survival. LV facilities may be less familiar with treatment regimens for AML, less likely to use novel treatment options, and be less familiar with the disease. We showed that treatment at an AC compared to CP, CCP and IN facilities improved survival. Given poor outcomes for AML, these results show the importance of going to AC and HV facilities with more experience in treating AML for improved outcomes. Disclosures Lai: Astellas: Speakers Bureau; Jazz: Speakers Bureau; Abbvie: Consultancy; Agios: Consultancy; Macrogenics: Consultancy.


2021 ◽  
Author(s):  
Liyuan Liu ◽  
Shan Wu ◽  
Dan Jiang ◽  
Yuliang Qu ◽  
Hongxia Wang ◽  
...  

Abstract Background: Abnormal expression of Circular RNAs (circRNAs) occurs in the occurrence and progression of colorectal cancer (CRC) and plays an important role in the pathogenesis of tumors. We combined bioinformatics and laboratory-validated methods to search for key circRNAs and possible potential mechanisms. Methods: Colorectal cancer tissues and normal paracancerous tissues were detected by microarray analysis and qRT-PCR validation, and differentially expressed circRNAs were screened and identified. The circRNA-miRNA-mRNA regulatory network (cirReNET) was constructed, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to ascertain the functions of circRNAs in CRCs. In addition, a protein-protein interaction (PPI) network of hub genes which acquired by string and plugin app CytoHubba in cytoscape was established. Validation of expression of hub genes was identified by GEPIA database. Results: 564 differentially expressed circRNAs which include 207 up-regulated and 357 down-regulated circRNAs were detected. The top 3 up-regulated circRNAs (hsa_circRNA_100833, hsa_circRNA_103828, hsa_circRNA_103831) and the top 3 down-regulated circRNAs (hsa_circRNA_103752, hsa_circRNA_071106, hsa_circRNA_102293) in chip analysis were chosen to be verified in 33 pairs of CRCs by qRT-PCR. The cirReNET include of 6 circRNAs, 19 miRNAs and 210 mRNA. And the targeted mRNAs were associated with cellular metabolic process, cell cycle and glandular epithelial cell differentiation and so on. 12 and 10 target hub genes were shown separately in upregulated circRNA-downregulated miRNA-upregulated mRNA (UcDiUm-RNA) group and downregulated circRNA-upregulated miRNA-downregulated mRNA (DcUiDm-RNA) group. Finally, we may have predicted and discovered several critical circRNA-miRNA-mRNA regulatory axes (cirReAXEs) which may play important roles in colorectal cancer. Conclusion: We constructed a cirReNET including 6 candidate circRNAs, which were crucial in CRCs, may become potential diagnostic markers and predictive indicators of CRCs, and we may provide a research direction for the pathogenesis of colorectal cancer.


2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang

Abstract Background: Lung cancer is one of the most common cancers, with high morbidity and mortality. MiRNAs are proved to play important roles in various human cancers. In our study, we aimed to explore the prognostic value of miR-181 in lung cancerMethods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression level of miR-181 in lung cancer tissues and the paired non-cancerous tissues. The relationship between miR-181 expression and clinicopathologic parameters were analyzed by chi-square test. Kaplan-Meier method with log rank test was applied for overall survival analysis. Furthermore, the Cox regression analyses were performed to evaluate the prognostic value of miR-181 in lung cancer.Results: Down-regulated miR-181 expression was observed in lung cancer tissues (P<0.001), moreover, its expression was significantly correlated with TNM stage (P=0.015) and metastasis (P=0.000). In addition, lung cancer patients with lower miR-181 expression level had poorer overall survival than those with higher expression (log rank test, P=0.011). Cox regression analysis suggested that miR-181 was an independent prognostic factor for lung cancer (HR=1.961, 95%CI=1.135-3.388, P=0.016).Conclusion: MiR-181 may be a tumor suppressor gene in lung cancer, which can predict outcomes for the patients.


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