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.

Thyroid Cancer Persistence in Patients with Unreliable Thyroglobulin Measurement: Circulating microRNA as Candidate Alternative Biomarkers

“…This is well in line with some previous reports demonstrating the up-regulation of miR-222, miR-221, and miR-146b in PTC patients compared to those with benign nodules and controls [ 23 , 24 , 25 , 31 , 32 , 33 , 34 , 35 , 36 , 45 ]. Rosignolo et al reported that the serum levels of circulating miR-221 were consistent with ATA responses to therapy in PTC patients, supporting their role in post-treatment monitoring [ 25 ].…”

“…Overall, among the different serum miRNAs tested in our study, miRNA 221, 222, and 146b emerged as the most suitable candidate biomarkers to complement imaging (i.e., nUS, Dx-WBS) in the post-operative monitoring of PTC patients with uninformative Tg. This is well in line with some previous reports demonstrating the up-regulation of miR-222, miR-221, and miR-146b in PTC patients compared to those with benign nodules and controls [23][24][25][31][32][33][34][35][36]45]. Rosignolo et al reported that the serum levels of circulating miR-221 were consistent with ATA responses to therapy in PTC patients, supporting their role in post-treatment monitoring [25].…”

“…Increasing evidence repeatedly demonstrated the key involvement of miRNAs in thyroid cancer, and an altered expression of tumor-associated miRNA has also been documented in thyroid cancer tissues [ 19 , 20 , 21 , 22 , 23 , 24 , 27 ]. Previous studies investigated the role of miRNAs (particularly miRNA 221, 222, and 146b) in differentiating between benign and malignant thyroid nodules and monitoring DTC patients [ 21 , 23 , 25 , 26 , 27 , 31 , 32 , 33 , 34 , 35 , 36 , 41 , 42 , 43 , 44 , 45 , 46 ] with sparse results, likely due to different methodological approaches to quantify the tissue expression of miRNAs. Recently, miRNAs have also been evaluated in body fluids like serum as they are quite stable being incorporated in microparticles [ 22 , 23 , 24 , 25 , 26 , 38 , 46 ], prompting us to evaluate their use as a circulating marker of disease persistence in PTC patients with “uninformative” thyroglobulin.…”

“…In particular, miR-221 and miR-222 are the two most extensively evaluated functional miRNAs in thyroid carcinoma [ 31 ]. Increasing evidence indicates that miR-221, miR-222, and miR-146b are upregulated in PTC [ 24 , 27 ] and their expression significantly predicts the outcome and prognosis of the cancer [ 24 , 27 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

Prognostic and therapeutic implication of m6A methylation in Crohn disease

“…Next, we identified 4 intersection genes from m6Acluster types. XPNPEP2 was one of the critical genes in thyroid cancer targeted by miR-222-3p, [ 53 ] and it was associated with lymph node metastasis in prostate and cervical cancers. [ 54 , 55 ] REEP6, an accessory protein, refined CXCR1-mediated cellular responses in lung cancer.…”