Development of a novel miR-3648-related gene signature as a prognostic biomarker in esophageal adenocarcinoma

Abstract

Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature. Methods:The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression analysis were applied to identify IRGs and to construct a prognostic signature and nomogram.Results: MiR-3648 was expectedly highly expressed in EA tumor tissues (P=2.6e-8), and related to the infiltration of activated natural killer cells (NK cells) and activated CD4 T lymphocytes (CD4 cells). A total of 70 miR-3648-targeted genes related to immune cell infiltration were identified. Among them, 4 genes (C10orf55, DLL4, PANX2, and NKAIN1) were closely related to overall survival (OS), and were thus selected to construct a 4-gene risk score (RS). The RS had a superior capability to predict OS [area under the curve (AUC) =0.740 for 1 year; AUC =0.717 for 3 years; AUC =0.622 for 5 years]. A higher score was indicative of a poorer prognosis than a lower score [hazard ratio (HR) =2.71; 95% confidence interval (CI): 1.45-5.09; P=0.002]. Furthermore, the nomogram formed by combining the RS and the TNM classification of malignant tumors (TNM stage) improved the accuracy of survival prediction [Harrell's concordance index (C-index) =0.698].Conclusions: MiR-3648 may play a critical role in EA pathogenesis. The novel 4-gene signature may serve as a prognostic tool to manage patients with EA.

The Expression Patterns and Implications of MALAT1, MANCR, PSMA3-AS1 and miR-101 in Esophageal Adenocarcinoma

“…Recent studies have revealed that additional miRNAs, including miR-421, miR-550a-1, and miR-3648, could serve as new prognostic biomarkers in EAC. These miRNAs play a significant role in EAC pathogenesis by suppressing proliferation, invasion, and migration in OE33 cells or by targeting immunerelated genes (IRGs) [36,37] It has been found that in many cancerous tumors, miR-101 is significantly downregulated compared to healthy tissues [17]. Our research outcomes validate this finding in the context of EAC tumors and positive lymph nodes, areas where there have been limited data on miR-101.…”

“…Recent studies have revealed that additional miRNAs, including miR-421, miR-550a-1, and miR-3648, could serve as new prognostic biomarkers in EAC. These miRNAs play a significant role in EAC pathogenesis by suppressing proliferation, invasion, and migration in OE33 cells or by targeting immune-related genes (IRGs) [ 36 , 37 ]…”

C10orf55, CASC2, and SFTA1P lncRNAs Are Potential Biomarkers to Assess Radiation Therapy Response in Head and Neck Cancers

“…The in vivo and in vitro results suggest an involvement of C10orf55 in tumor cell proliferation and migration [ 40 ]. It has also been investigated in acute myeloid leukemia and in complete remission of the disease, following treatment with chemotherapeutics [ 41 ]. Dysregulation of this lncRNA after successful treatment with both chemotherapy and radiotherapy offers hope for new diagnostic methods and creates room for more accurate studies.…”

NKAIN1, as an oncogene, promotes the proliferation and metastasis of breast cancer, affecting its prognosis

“…NKAIN1 can be optimized as a practical gene to predict the prognosis of prostate cancer and response rate to immunotherapy 15 . In addition, NKAIN1 expression levels are known to increase in esophageal adenocarcinoma and positively correlate with its poor prognosis 16 . However, the association between NKAIN1 and human breast cancer remains unclear.…”

“…15 In addition, NKAIN1 expression levels are known to increase in esophageal adenocarcinoma and positively correlate with its poor prognosis. 16 However, the association between NKAIN1 and human breast cancer remains unclear.…”