Dataset Information

Prognostic and Immune-Infiltrate Significance of miR-222-3p and Its Target Genes in Thyroid Cancer.

ABSTRACT: Thyroid cancer (THCA) is a common endocrine malignancy. With increasing incidence and low mortality, balancing the therapeutic approach is an inevitable issue. This study aimed to confirm the role of miR-222-3p and its target genes in THCA survival and immune infiltration. From different expression analyses based on the GEO and TCGA databases, we predicted and subsequently identified the key target genes of miR-222-3p. We then explored the expression, enrichment, pairwise correlation, protein expression, survival analysis, principal component analysis, and immune significance of the critical genes using bioinformatics analysis. The present study demonstrated that NEGR1, NTNG1, XPNPEP2, NTNG2, CD109, OPCML, and PRND are critical genes. The miR-222-3p was highly expressed, probably leading to low NEGR1 and high PRND expression in THCA tissues. Low NEGR1 expression indicated favorable prognosis in THCA patients, and high PRND expression indicated poor prognosis. Seven critical genes were significantly related to gender, age, race, tumor stage, and lymph node metastasis. In addition, the seven-gene biomarker exhibited a certain diagnostic value. Finally, CD109 expression was closely correlated with immune cells, especially B cells and CD4⁺ T cells. The miR-222-3p and its critical target genes could be promising biomarkers for the prognosis of THCA and may emerge as key regulators of immune infiltration in THCA.

SUBMITTER: Zhang T

PROVIDER: S-EPMC8562566 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Prognostic and Immune-Infiltrate Significance of miR-222-3p and Its Target Genes in Thyroid Cancer.

Zhang Taofeng T Chen Yihuan Y Lin Weixun W Zheng Jiehua J Liu Yiyuan Y Zou Juan J Cai Jiehui J Chen Yaokun Y Li Zhiyang Z Chen Yexi Y

Frontiers in genetics 20211019

Thyroid cancer (THCA) is a common endocrine malignancy. With increasing incidence and low mortality, balancing the therapeutic approach is an inevitable issue. This study aimed to confirm the role of miR-222-3p and its target genes in THCA survival and immune infiltration. From different expression analyses based on the GEO and TCGA databases, we predicted and subsequently identified the key target genes of miR-222-3p. We then explored the expression, enrichment, pairwise correlation, protein ex ...[more]

PMID: 34737762

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Project description:BackgroundMicroRNA-221-3p (miR-221-3p) facilitates the advancement of breast cancer (BC) through the induction of epithelial-mesenchymal transition (EMT). Our research aimed to utilize bioinformatics to discover possible EMT-related target genes (ETGs) of miR-221-3p and examine their roles in breast cancer.MethodsWe employed bioinformatics techniques to identify ten key ETGs of miR-221-3p. Subsequently, we conducted an extensive analysis of both miR-221-3p and the ten ETGs, including clinical significance and immune characteristics.ResultsThe expression of miR-221-3p was notably higher in Basal-like BC compared to other subtypes and adjacent normal tissue. Our pathway analysis suggested that miR-221-3p might regulate EMT through the MAPK signaling pathway by targeting its ETGs. Among the ETGs, seven core genes (EGFR, IGF1, KDR, FGF2, KIT, FGFR1, and FGF1) exhibited downregulation in BC. Conversely, ERBB2, SDC1, and MMP14 showed upregulation in BC and displayed potential diagnostic value. The analysis of prognostication indicated that increased levels of SDC1 and MMP14 were correlated with an unfavorable prognosis, whereas elevated expression of KIT was associated with a more favorable prognosis. The infiltration of various immune cells and the expression of immune checkpoint genes (ICGs) exhibited positive correlations with most ETGs and miR-221-3p. SDC1 exhibited a greater tumor mutational burden (TMB) score, while ERBB2, KDR, FGF2, KIT, FGFR1, and FGF1 showed lower TMB scores. Furthermore, decreased ERBB2 and KDR expression levels were correlated with elevated microsatellite instability (MSI) scores. Elevated expression of ETGs was linked to decreased mRNA stemness indices (mRNAsi), whereas miR-221-3p displayed the opposite pattern. Most ETGs and miR-221-3p expression exhibited a negative correlation with IC50 values for drugs. Among the ETGs, amplification was the most significant genetic alteration, except for IGF1.ConclusionIn conclusion, miR-221-3p acts as a unique indicator for Basal-like BC. The examination revealed ten essential ETGs of miR-221-3p, some of which show potential as diagnostic and prognostic markers. The in-depth examination of these ten ETGs and miR-221-3p indicates their participation in the development of BC, emphasizing their promise as innovative targets for therapy in BC patients.

Project description:Background and objectivesSolitary fibrous tumors (SFTs) are morphologically heterogeneous tumors characterized by the NAB2::STAT6 gene fusion. Clinical outcomes may vary widely, and while most cases have favorable outcomes, some can progress to aggressive disease, manifesting as recurrence and metastasis, and ultimately resulting in patient death. Herein, we analyze the immunological tumor microenvironment (ITME) of SFTs, aiming to determine its prognostic value and correlation with established risk stratification systems (RSSs).MethodsA retrospective observational multicenter study of 52 fusion-confirmed SFTs with clinical follow-up data. Immunohistochemical analysis including CD163, CD68, CD3, CD8, CD20, PDL-1, PD-1, and LAG1 were evaluated in tissue microarrays, using an analog scale with scores ranging from 0 to 3 (0 = ≤9, 1 = 10-49, 2 = 50-99, and 3 = >100 positive cells per 10 high-power fields). The expression of these markers was correlated with clinical outcomes, morphological characteristics previously evaluated in whole slide tissue sections (hypercellularity/hypocellularity, round-oval or spindle dominant constituent cell (DCC) morphology, and necrosis), Ki67, overall survival, and RSS.ResultsOnly one of the fifty-two cases studied showed progression. In the multivariate analysis, neither the presence nor absence of immune cells (B-lymphocytes, T-lymphocytes, and macrophages) showed any association with the assessed RSSs (Demicco, Sugita, G-score, and Huang). Interestingly, the case that showed progression had high immune infiltrate with expression of CD68, CD163, CD8, and CD20 markers (score of 3). Round-oval cell morphology was associated with the presence of higher levels of CD163 macrophages. Lastly, the scant presence of CD20+ lymphocytes correlated with less necrosis, and cases with higher PDL-1 expression correlated with increased Ki67 values. All cases were negative for LAG-1 and PD-1.ConclusionsSFT ITME components correlated with independent variables with prognostic significance. Nevertheless, ITME did not correlate with RSS scores.

Project description:IntroductionThyroid cancer is a very common malignant tumor in the endocrine system, while the incidence of papillary thyroid carcinoma (PTC) throughout the world also shows a trend of increase year by year. In this study, we constructed two models: ICIscore and Riskscore. Combined with these two models, we can make more accurate and reasonable inferences about the prognosis of PTC patients.MethodsWe selected 481 PTC samples from TCGA and 147 PTC samples from GEO (49 samples in GSE33630, 65 samples in GSE35570 and 33 samples in GSE60542). We performed consistent clustering for them and divided them into three subgroups and screened differentially expressed genes from these three subgroups. Then we divided the differential genes into three subtypes. We also distinguished the up-regulated and down-regulated genes and calculated ICIscore for each PTC sample. ICIscore consists of two parts: (1) the PCAu was calculated from up-regulated genes. (2) the PCAd was calculated from down-regulated genes. The PCAu and PCAd of each sample were the first principal component of the relevant gene. What's more, we divided the patients into two groups and constructed mRNA prognostic signatures. Additionally we also verified the independent prognostic value of the signature.ResultsThough ICIscore, we were able to observe the relationship between immune infiltration and prognosis. The result suggests that the activation of the immune system may have both positive and negative consequences. Though Riskscore, we could make more accurate predictions about the prognosis of patients with PTC. Meanwhile, we also generated and validated the ICIscore group and Riskscore group respectively.ConclusionAll the research results show that by combining the two models constructed, ICIscore and Riskscore, we can make a more accurate and reasonable inference about the prognosis of patients with clinical PTC patients. This suggests that we can provide more effective and reasonable treatment plan for clinical PTC patients.

Dataset Information

Prognostic and Immune-Infiltrate Significance of miR-222-3p and Its Target Genes in Thyroid Cancer.

Publications

Prognostic and Immune-Infiltrate Significance of miR-222-3p and Its Target Genes in Thyroid Cancer.

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