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BACKGROUND: In recent years, immunotherapy has made great progress, and the regulatory role of epigenetics has been verified. However, the role of 5-methylcytosine (m(5)C) in the tumor microenvironment (TME) and immunotherapy response remains unclear. METHODS: Based on 11 m(5)C regulators, we evaluated the m(5)C modification patterns of 572 lung adenocarcinoma (LUAD) patients. The m(5)C score was constructed by principal component analysis (PCA) algorithms in order to quantify the m(5)C modification pattern of individual LUAD patients. RESULTS: Two m(5)C methylation modification patterns were identified according to 11 m(5)C regulators. The two patterns had a remarkably distinct TME immune cell infiltration characterization. Next, 226 differentially expressed genes (DEGs) related to the m(5)C phenotype were screened. Patients were divided into three different gene cluster subtypes based on these genes, which had different TME immune cell infiltration and prognosis characteristics. The m(5)C score was constructed to quantify the m(5)C modification pattern of individual LUAD patients. We found that the high m(5)C score group had a better prognosis. The role of the m(5)C score in predicting prognosis was also verified in the dataset GSE31210. CONCLUSIONS: Our study revealed that m(5)C modification played a significant role in TME regulation of LUAD. Investigation of the m(5)C regulation mode may have some implications for tumor immunotherapy in the future.

Background: The optimal therapeutic strategy in locally advanced esophageal squamous cell carcinoma (ESCC) primarily treated by surgery remains unknown. This study was designed to evaluate the impact of postoperative chemoradiotherapy and postoperative sequential chemoradiotherapy on survival in this population. Methods: The study included a total of 228 consecutive patients who underwent radical esophagectomy and were confirmed to have stage pT3–4 or pN+ ESCC from September 2011 to September 2017 at our institution. All patients received postoperative radiotherapy with or without concurrent or sequential chemotherapy after esophagectomy. Univariate and multivariate analyses were used to compare the survival of patients with postoperative radiotherapy, postoperative concurrent chemoradiotherapy, and postoperative sequential chemoradiotherapy. Results: After a median follow-up of 52 months, the 3- and 5-year overall survival (OS) rates were 70.2% [95% confidence interval (CI), 63.7–76.7%] and 62.2% (95% CI, 54.6–69.8%), respectively. The disease-free survival (DFS) rates at 3 and 5 years were 65.2% (95% CI, 58.7–71.7%) and 55.2% (95% CI, 47.6–62.8%), respectively. The 3- and 5-year locoregional recurrence-free survival (LRFS) rates were 65.1% (95% CI, 58.4–71.8%) and 55.5% (95% CI, 47.7–63.3%). Of the 228 patients, 38 (16.7%) had distant metastases. Subgroup analysis showed that being male and having a higher T stage were independent poor prognostic factors for OS and DFS in patients with pN+ or stage III + IVA ESCC. The results also showed that in patients with stage III + IVA ESCC, the DFS of the patients in the concurrent chemotherapy (CCT) group was improved compared with that in the no CCT group [hazard ratio (HR), 0.551; 95% CI, 0.323–0.938; P=0.028]. Multivariate analysis showed that sequential chemoradiotherapy was associated with poor LRFS (HR, 2.312; 95% CI, 1.078–4.959; P=0.031), especially in stage T3–4 patients, and it was also related to the poor DFS (HR, 1.781; 95% CI, 1.086–2.921; P=0.022) in patients with stage T3–4 ESCC. Conclusions: In patients with locally advanced ESCC, those who underwent sequential chemoradiotherapy had a worse LRFS. Postoperative concurrent chemoradiotherapy was the most effective adjuvant therapy for resected stage III–IVA ESCC. In addition, being male, having a higher T stage, and being node-positive were independent poor prognostic factors for OS and DFS.