scholarly journals Integrated Analysis of MicroRNA (miRNA) and mRNA Profiles Reveals Reduced Correlation between MicroRNA and Target Gene in Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xingsong Li ◽  
Xiaokang Yu ◽  
Yuting He ◽  
Yuhuan Meng ◽  
Jinsheng Liang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Mirna Target ◽  
Target Gene ◽  
Target Genes ◽  
Integrated Analysis ◽  
Cancer Type ◽  
Gene Pairs ◽  
Cancer Types

Background. Accumulating evidences demonstrated that microRNA-target gene pairs were closely related to tumorigenesis and development. However, the correlation between miRNA and target gene was insufficiently understood, especially its changes between tumor and normal tissues. Objectives. The aim of this study was to evaluate the changes of correlation of miRNAs-target pairs between normal and tumor. Materials and Methods. 5680 mRNA and 5740 miRNA expression profiles of 11 major human cancers were downloaded from the Cancer Genome Atlas (TCGA). The 11 cancer types were bladder urothelial carcinoma, breast invasive carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and thyroid carcinoma. For each cancer type, we firstly obtained differentially expressed miRNAs (DEMs) and genes (DEGs) in tumor and then acquired critical miRNA-target gene pairs by combining DEMs, DEGs and two experimentally validated miRNA-target interaction databases, miRTarBase and miRecords. We collected samples with both miRNA and mRNA expression values and performed a correlation analysis by Pearson method for miRNA-target pairs in normal and tumor, respectively. Results. We totally got 4743 critical miRNA-target pairs across 11 cancer types, and 4572 of them showed weaker correlation in tumor than in normal. The average correlation coefficients of miRNA-target pairs were different greatly between normal (-0.38 ~ -0.61) and tumor (-0.04 ~ -0.26) for 11 cancer type. The pan-cancer network, which consisted of 108 edges connecting 35 miRNAs and 89 target genes, showed the interactions of pairs appeared in multicancers. Conclusions. This comprehensive analysis revealed that correlation between miRNAs and target genes was greatly reduced in tumor and these critical pairs we got were involved in cellular adhesion, proliferation, and migration. Our research could provide opportunities for investigating cancer molecular regulatory mechanism and seeking therapeutic targets.

335 DIFFERENTIALLY EXPRESSED MICRORNAS AND PREDICTIVE TARGET GENES IN BASALOID SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS

2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Jiro Nakamura ◽  
Shinji Furuya ◽  
Kotaro Hagio ◽  
Suguru Maruyama ◽  
Kensuke Shiraishi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Validation Study ◽  
Target Gene ◽  
Target Genes ◽  
Basaloid Squamous Cell Carcinoma ◽  
Carcinoma Of The Esophagus ◽  
Total Rna ◽  
Basaloid Squamous

Abstract   Background/Aim: Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Esophageal squamous cell carcinoma (ESCC) is considered as one of the most aggressive carcinomas of the gastrointestinal tract. Basaloid squamous cell carcinoma of the esophagus (BSCCE) is reported to have a poorer prognosis compared to conventional ESCC. The current study aimed to elucidate molecular differences between BSCCE and ESCC, using miRNA profiling and predictive target gene searching. Methods Materials and Methods: Four BSCCE and 94 ESCC patients who underwent esophagectomy were selected for this study. Cell lines were used for target gene validation. Total RNA samples, extracted from formalin-fixed paraffin-embedded blocks, were used for microarray profiling and validation of the miRNAs, selecting the candidate target genes, and elucidating their clinicopathological features. Furthermore, total RNA samples, extracted from miRNA mimic- and inhibitor-transfected cells in cell line experiments, were used for target gene validation. Both miRNA and mRNA quantifications were performed by quantitative reverse transcription-polymerase chain reaction. Results The microarray analysis revealed seven highly expressed miRNAs (miR-205-5p, −4732-5p, −1246, −3687, −3175, −6087, and − 1587) in the BSCCE patients when compared with control. We selected miR-4732-5p and − 3687 for the validation study, and target gene investigations were conducted for miR-3687 ultimately. Several candidates were selected after searching for the target genes via TargetScan and in the literature. Through a pilot and a validation study, progesterone receptor membrane component 2 (PGRMC2) was identified as a target gene. Further investigations revealed that PGRMC2 was associated with tumor size clinicopathologically. Conclusion miR-3687 may constitute a candidate marker of aggressiveness in BSCCE, and PGRMC2 is one of its target genes. Moreover, the gene may play a role in cell proliferation and local progression. Although the current study included only a small number of samples, this is the first report regarding differentially expressed miRNAs and predictive target genes in BSCCE patients.

PIK3CA-TP53 co-mutation as a biomarker of overall survival in malignant tumor.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15001-e15001
Author(s):  
Hongyan Wang ◽  
Xiaopeng Zhao ◽  
Xu He ◽  
Miao Wang ◽  
Haoran Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Double Mutant ◽  
Malignant Tumors ◽  
Single Gene ◽  
Hazard Ratio ◽  
Cancer Type ◽  
Cancer Types

e15001 Background: Overall survival (OS) is an important endpoint, with the advantage that there is minimal ambiguity in defining an OS event; the patient is either alive or dead. Some single gene mutations, such as TP53, were identified as important predictors of shorter OS in malignant tumors. However, the relationship between gene co-mutation and OS of malignant tumors is poorly defined. Methods: Genomic and OS data were derived from The Cancer Genome Atlas (TCGA) databases. We defined the double-mutant gene pair as “hit pair” in the specific cancer type if statistically significant OS difference was observed in at least one of three comparison (double-mutant samples vs gene A-only-mutant samples; double-mutant samples vs gene B-only-mutant samples; gene A-only-mutant samples vs gene B-only-mutant samples). Results: PIK3CA-TP53 co-mutation was evaluated as “hit pair” in seven cancer types: GBM (Glioblastoma multiforme), HNSC (Head and neck squamous cell carcinoma), LUSC (Lung squamous cell carcinoma), SARC (Sarcoma), SKCM (Skin cutaneous melanoma), UCEC (Uterine corpus endometrial carcinoma), and UCS (Uterine carcinosarcoma). In SARC and SKCM, the expected hazard ratio was higher in both-mutant group than TP53-only-mutant group, and neither genes were correlated with OS. Especially in SKCM, after we took “neither” group (both genes were wild-type) into comparison, hazard ratio of both-mutant group was significantly higher than neither group. Single-gene mutation didn’t make difference on hazard ratio, which indicated that the both-mutant interaction made the leading contribution. In GBM, LUSC, and UCS, the significant difference of hazard ratio between TP53-only-mutant group and PIK3CA-only-mutant group was neutralized in the both-mutant group, to some extent equivalent to “average effect (OS curve of double-mutant group was between that of only single gene mutant groups)". For PIK3CA-TP53 in HNSC, both-mutant group and TP53-only-mutant group carried with a higher hazard ratio than PIK3CA-only-mutant group. It suggested that the increasing hazard ratio in both-mutant group might be resulted from TP53 mutation. For the circumstance in UCEC, TP53 and PIK3CA were testified to be correlated with higher and lower hazard ratio, respectively and both-mutant group and TP53-only-mutant group both with significantly higher hazard ratio than PIK3CA-only-mutant group, which further verified the greater strength of TP53 than PIK3CA in both-mutant group. Conclusions: In summary, our study identified PIK3CA-TP53 co-mutation as a predictor of OS in seven cancer types: GBM, HNSC, LUSC, SARC, SKCM, UCEC, and UCS, especially in SARC and SKCM.

193 Differences in thyroid immune-related adverse events between lung cancer types, a retrospective analysis

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A208-A208
Author(s):  
Rahim Jiwani ◽  
Heather Brody ◽  
Yuxuan Mao ◽  
Elisabeth Lee ◽  
Rita Rehana ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Thyroid Dysfunction ◽  
Cohort Analysis ◽  
Cancer Type ◽  
Chi Square ◽  
Cancer Types

BackgroundImmune modulation of the PD-1/PD-L1 pathway is a promising treatment of various malignancies however, alteration of the pathway is known to cause many immune related adverse events (irAEs) including thyroid dysfunction. Whether the frequency of thyroid irAEs differ between lung cancer types has not yet been studied.MethodsA total of three hundred twenty-nine lung cancer patients treated with immunotherapy at East Carolina University between April 2014 and July 2019 were included in a retrospective cohort analysis. Baseline TSH and TSH at each treatment cycle were recorded along with the type of lung cancer, specific agent used, timing of thyroid dysfunction and need for levothyroxine replacement. The frequency of thyroid irAEs as defined by TSH < 0.4 or > 4.0 and its relationship with lung cancer types were analyzed using chi square tests and logistic regression.ResultsOf the three hundred twenty-nine patients; 54.4% had adenocarcinoma, 31.6% had squamous cell carcinoma, 11.3% had small cell carcinoma and 2.7% had poorly differentiated lung cancer. Overall, 135 patients (41.0%) developed thyroid irAEs (table 1). Pearson’s chi square test was used to compare the frequencies of thyroid irAEs for each type of lung cancer against all other lung cancer types. Patients with squamous cell carcinoma developed significantly less thyroid irAEs (32.7%), compared to all other lung cancers (44.9%), X2 (1, N = 329) = 4.4, p = 0.037. Conversely, patients with lung cancer types other than squamous cell carcinoma were more likely to develop thyroid irAEs, OR = 1.68 (95% CI: 1.03 – 2.73).ConclusionsThyroid irAEs occurred significantly less frequently in patients with squamous cell carcinoma than those with other lung cancer types. This analysis may allow clinicians to better identify patients more likely to develop irAE thyroid dysfunction based on lung cancer type.Abstract 193 Table 1Frequency of lung cancer type and thyroid dysfunction within each group

scholarly journals Significance of miR-141 and miR-340 in cervical squamous cell carcinoma

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 864-872
Author(s):  
Wenting Li ◽  
Bo Yang ◽  
Yiqun Li ◽  
Cuicui Wang ◽  
Xinzhi Fang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Gene ◽  
Squamous Epithelium ◽  
Figo Stage ◽  
Cervical Squamous Cell Carcinoma ◽  
Squamous Intraepithelial Lesion ◽  
Nerve Invasion ◽  
Intraepithelial Lesion

Abstract Background We investigated the expression and clinical significance of miR-141 and miR-340 in cervical squamous cell carcinoma (CSCC). Methods Expression of miR-141 and miR-340 in CSCC, high-grade squamous intraepithelial lesion (HSIL), and normal cervical squamous epithelium were detected by qRT-PCR. PTEN was assessed by immunohistochemistry. Their relationship with clinicopathological features was analyzed. Results The changes of miR-141 and miR-340 were different in CSCC, HSIL, and normal squamous epithelium (P = 0.030). miR-141 expression was statistically significant in gross type, differentiation, uterine corpus invasion, nerve invasion, vagina invasion, and FIGO stage in CSCC (P < 0.05). miR-340 expression was related to tumor size, differentiation, nerve invasion, lymph node metastasis, and FIGO stage in CSCC (P < 0.05). miR-141 and miR-340 expressions were statistically significant in different ages (P < 0.05) in HSIL. The AUC of miR-141 in CSCC diagnosis and that of miR-340 in HSIL diagnosis were 0.893 and 0.764, respectively. The sensitivity and the specificity of miR-141 for diagnosis of CSCC were 95.0% and 60.8%, respectively, while those of miR-340 for diagnosis of HSIL were 90.0 and 48.6%, respectively. miR-141 and miR-340 expressions are associated with PTEN expression (P = 0.002 and P < 0.001). Conclusion miR-141 and miR-340 may be associated with their target gene PTEN and involved in the carcinogenesis of cervical squamous epithelium.

scholarly journals Integrated Analysis Reveals ENDOU as a Biomarker in Head and Neck Squamous Cell Carcinoma Progression

2021 ◽  
Vol 10 ◽  
Author(s):  
Chengzhi Xu ◽  
Yunbin Zhang ◽  
Yupeng Shen ◽  
Yong Shi ◽  
Ming Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Neck Squamous Cell Carcinoma ◽  
Integrated Analysis ◽  
Pathway Enrichment Analysis ◽  
And Migration ◽  
Proliferation And Migration

BackgroundHead and neck squamous cell carcinoma (HNSCC) is a leading cancer with high morbidity and mortality worldwide. The aim is to identify genes with clinical significance by integrated bioinformatics analysis and investigate their function in HNSCC.MethodsWe downloaded and analyzed two gene expression datasets of GSE6631 and GSE107591 to screen differentially expressed genes (DEGs) in HNSCC. Common DEGs were functionally analyzed by Gene ontology and KEGG pathway enrichment analysis. Protein-protein interaction (PPI) network was constructed with STRING database and Cytoscape. ENDOU was overexpressed in FaDu and Cal-27 cell lines, and cell proliferation and migration capability were evaluated with MTT, scratch and transwell assay. The prognostic performance of ENDOU and expression correlation with tumor infiltrates in HNSCC were validated with TCGA HNSCC datasets.ResultsNinety-eight genes shared common differential expression in both datasets, with core functions like extracellular matrix organization significantly enriched. 15 genes showed prognostic significance, and COBL and ENDOU serve as independent survival markers in HNSCC. In-vitro ENDOU overexpression inhibited FaDu and Cal-27 cells proliferation and migration, indicating its tumor-suppressing role in HNSCC progression. GSEA analysis indicated ENDOU down-stream pathways like DNA replication, mismatch repair, cell cycle and IL-17 signaling pathway. ENDOU showed relative lower expression in HNSCC, especially HPV-positive HNSCC samples. At last, ENDOU showed negative correlation with tumor purity and tumor infiltrating macrophages, especially M2 macrophages.ConclusionThis study identified ENDOU as a biomarker with prognostic significance in HNSCC progression.

Autophagy regulation patterns characterization identifies immune phenotypes and immunotherapy response in head and neck squamous cell carcinoma (HNSCC)

2020 ◽  
Author(s):  
Bo Ma ◽  
Hui Li ◽  
Mingzhu Zheng ◽  
Rui Cao ◽  
Riyue Yu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Scoring System ◽  
Clustering Algorithm ◽  
Neck Squamous Cell Carcinoma ◽  
Integrated Analysis ◽  
Molecular Characteristics ◽  
Immune Phenotypes

Abstract BackgroundAutophagy degraded and recycled cytoplasmic components to maintain cellular homeostasis under stress conditions, which was recognized as double-edged sword in oncogenesis and novel target in cancer treatment. However, comprehensive analysis of the relationship between autophagy regulation and immunity has not been reported yet. MethodsUnsupervised consensus clustering algorithm was used to identify autophagy regulation patterns. LASSO cox regression algorithm was used to build a scoring system (ATGscore) to represent the individual autophagy regulation pattern. Then integrated analysis of autophagy regulation patterns and ATGscore was performed.ResultsWe have successful depicted five autophagy regulation patterns and established a scoring system (ATGscore) to represent it, which was shown to be significantly correlated with TIME infiltration, immune phenotypes, molecular subtypes, and genetic variation, etc. in 1165 head and neck squamous cell carcinoma (HNSCC) patients. Moreover, ATGscore was an independent prognostic factor and potent predictor for clinical response to immune-checkpoint inhibitors (ICIs) targeting immunotherapy. ConclusionUnderstanding the molecular characteristics of autophagy regulation patterns in HNSCC could help us to depict the underlying mechanism of tumour immunity and lay a solid foundation on combination of autophagy targeting therapies and immunotherapies for clinical application in HNSCC.

scholarly journals Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2071 ◽  
Author(s):  
Patricia P. Reis ◽  
Sandra A. Drigo ◽  
Robson F. Carvalho ◽  
Rainer Marco Lopez Lapa ◽  
Tainara F. Felix ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Target Genes ◽  
Lung Squamous Cell Carcinoma ◽  
High Specificity ◽  
Mirna Signature ◽  
Lung Tumorigenesis ◽  
Lung Cancer Patients

Background: Micro(mi)RNAs, potent gene expression regulators associated with tumorigenesis, are stable, abundant circulating molecules, and detectable in plasma. Thus, miRNAs could potentially be useful in early lung cancer detection. We aimed to identify circulating miRNA signatures in plasma from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and to verify whether miRNAs regulate lung oncogenesis pathways. Methods: RNA isolated from 139 plasma samples (40 LUAD, 38 LUSC; 61 healthy/non-diseased individuals) were divided into discovery (38 patients; 21 controls for expression quantification using an 800-miRNA panel; Nanostring nCounter®) and validation (40 patients; 40 controls; TaqMan® RT-qPCR) cohorts. Elastic net, Maximizing-R-Square Analysis (MARSA), and C-Statistics were applied for miRNA signature identification. Results: When compared to healthy individuals, 580 of 606 deregulated miRNAs in LUAD and 221 of 226 deregulated miRNAs in LUSC had significantly increased levels. Among the 10 most significantly overexpressed miRNAs, 6 were common to patients with LUAD and LUSC. Further analysis identified three signatures composed of 12 miRNAs. Signatures included miRNAs commonly overexpressed in patient plasma. Enriched pathways included target genes modulated by three miRNAs in the C-Statistics signature: miR-16-5p, miR-92a-3p, and miR-451a. Conclusions: The 3-miRNA signature (miR-16-5p, miR-92a-3p, miR-451a) had high specificity (100%) and sensitivity (84%) to predict cancer (LUAD and LUSC). These miRNAs are predicted to modulate genes and pathways with known roles in lung tumorigenesis, including EGFR, K-RAS, and PI3K/AKT signaling, suggesting that the 3-miRNA signature is biologically relevant in adenocarcinoma and squamous cell carcinoma of the lung.

scholarly journals CAFE MOCHA: An Integrated Platform for Discovering Clinically Relevant Molecular Changes in Cancer—An Example of Distant Metastasis– and Recurrence-Linked Classifiers in Head and Neck Squamous Cell Carcinoma

2018 ◽  
pp. 1-11
Author(s):  
Neeraja M. Krishnan ◽  
Mohanraj I ◽  
Janani Hariharan ◽  
Binay Panda
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cancer Genome ◽  
Neck Squamous Cell Carcinoma ◽  
Cancer Type ◽  
Molecular Signatures ◽  
Molecular Changes ◽  
Statistical Framework

Purpose With large amounts of multidimensional molecular data on cancers generated and deposited into public repositories such as The Cancer Genome Atlas and International Cancer Genome Consortium, a cancer type agnostic and integrative platform will help to identify signatures with clinical relevance. We devised such a platform and showcase it by identifying a molecular signature for patients with metastatic and recurrent (MR) head and neck squamous cell carcinoma (HNSCC). Methods We devised a statistical framework accompanied by a graphical user interface–driven application, Clinical Association of Functionally Established MOlecular CHAnges ( CAFE MOCHA; https://github.com/binaypanda/CAFEMOCHA), to discover molecular signatures linked to a specific clinical attribute in a cancer type. The platform integrates mutations and indels, gene expression, DNA methylation, and copy number variations to discover a classifier first and then to predict an incoming tumor for the same by pulling defined class variables into a single framework that incorporates a coordinate geometry–based algorithm called complete specificity margin-based clustering, which ensures maximum specificity. CAFE MOCHA classifies an incoming tumor sample using either its matched normal or a built-in database of normal tissues. The application is packed and deployed using the install4j multiplatform installer. We tested CAFE MOCHA in HNSCC tumors (n = 513) followed by validation in tumors from an independent cohort (n = 18) for discovering a signature linked to distant MR. Results CAFE MOCHA identified an integrated signature, MR44, associated with distant MR HNSCC, with 80% sensitivity and 100% specificity in the discovery stage and 100% sensitivity and 100% specificity in the validation stage. Conclusion CAFE MOCHA is a cancer type and clinical attribute agnostic statistical framework to discover integrated molecular signatures.

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