Objective. Increasing studies suggest that necroptosis is correlated with tumor progression. And aberrant microRNA (miRNA) expression plays a vital role in various tumors. Thus, we are committed to exploring a necroptosis-associated miRNA signature to serve as a prognostic biomarker in colon adenocarcinoma (COAD). Data Sources and Methods. In the current study, The Cancer Genome Atlas (TCGA) database was used to download the miRNA and mRNA expression profiles and clinical information of samples. All patients were stochastically assigned to TCGA-train and TCGA-test clusters. Subsequently, we established a prognostic signature comprised of necroptosis-related miRNAs (NR-mis) via LASSO-Cox regression and then developed a nomogram signature composed of the prognostic signature and clinical factors. Corresponding prognostic values were evaluated. Functional analysis, tumor microenvironment (TME), and chemosensitivity of risk subgroups were also identified. Results. The prognostic signature based on miR-141-3p, miR-148a-3p, miR-16-5p, and miR-200a-5p was closely associated with overall survival (OS) of samples and tumor metastasis in COAD. The Area Under Curve (AUC) was 0.605, 0.721, and 0.752 in TCGA-train cluster , 0.661, 0.613, and 0.695 in the TCGA-test cluster at 1, 3, and 5 years, respectively. The C-index for nomogram signature was 0.754. Functional analysis showed the remarkable enrichment of the signature-dependent miRNAs in tumor progression and immune response. And two risk subgroups were correlated with the distinct immune infiltration and immune checkpoints. In addition, the high-risk subgroup is more sensitive to cisplatin, doxorubicin, etoposide, and gemcitabine. Conclusions. Necroptosis-related miRNAs play a crucial role in the prognosis, metastasis, immune status, and drug sensitivity in COAD.

N7-Methylguanosine (m7G) is an RNA modification serving as a key part of colon cancer development. Thus, a comprehensive analysis was executed to explore prognostic roles and associations with the immune status of the m7G-related lncRNA (m7G-RNAs) in colon adenocarcinoma (COAD). Identification of m7G-RNAs was achieved via Pearson’s correlation analysis of lncRNAs in the TCGA-COAD dataset and m7G regulators. A prognostic signature was developed via LASSO analyses. ESTIMATE, CIBERSORT, and ssGSEA algorithms were utilized to assess immune infiltration between different risk groups. Survival analysis suggested the high-risk group possesses poor outcomes compared with the low-risk group. According to the ROC curves, the m7G-RNAs signature exhibited a reliable capability of prediction (AUCs at 1, 3, and 5 years were 0.770, 0.766, and 0.849, respectively). Multivariate hazard analysis proved that the signature was an independent predictive indicator for OS. Moreover, the risk score was related to infiltration levels of naïve B cells, CD4+ memory T cells, and resting NK cells. The result revealed the prognostic value of m7G modification in COAD and provided a novel perspective on personalized immunotherapy strategies.