Breast cancer (BC) displays striking genetic, epigenetic and phenotypic diversity. N6-methyladenosine (m6A) in mRNA has emerged as a crucial epitranscriptomic modification that controls cancer self-renewal and cell fate. However, the key enzymes of m6A expression and function in human breast carcinogenesis remain unclear. The expression of m6A methylases (METTL3, METTL14 and WTAP) and demethylases (FTO and ALKBH5) were analyzed by using ONCOMINE and The Cancer Genome Atlas databases and in 36 pairs of BC and adjacent non-cancerous tissue. The level of m6A in BC patients was detected by ELISA, and the function of m6A was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and transwell assay. The database of bc-GenExMiner v4.0, Kaplan-Meier Plotter and cBioPortal were queried for correlation, mutation and prognosis analysis of BC. The m6A methylases and demethylases were dysregulated in several major malignant tumors. Specifically, the expression of all m6A methylases was reduced in BC as compared with normal controls, but the demethylase ALKBH5 was induced in ONCOMINE databases and confirmed in clinical patients. METTL14 expression was positively correlated with METTL3 expression, and both showed high expression in normal breast-like and luminal-A and -B BC. Functionally, reducing m6A expression by overexpressing METTL14 and/or knockdown of ALKBH5 could inhibit breast cell viability, colony formation and cell migration. Furthermore, Kaplan-Meier, meta-analysis and univariate Cox assay showed that the expression of m6A members including METTL3, METTL14, WTAP and FTO but not their gene mutation and amplification, was tightly associated with cancer progression and poor survival. Changes of m6A modulators reduced m6A may promote tumorigenesis and predict poor prognosis in BC.

Background It is difficult to determine the lymph node metastasis of patients with clinically negative lymph nodes (cN0) non-small cell lung cancer (NSCLC) before surgery. The purpose of this study is to investigate risk factors of lymph node metastasis in cN0 NSCLC, thereby to identify the surgical indications for lymph node dissection in cN0 NSCLC. Methods We conducted a retrospective study of patients with tumor size <= 30 mm who underwent radical resection of NSCLC. Binary logistic regression analysis was applied to predict risk factors for lymph node metastasis, and subject operating characteristics (ROC) curve was used to evaluate the independent risk factors. Results Overall, 44 patients (6.8%) with cN0 NSCLC had lymph node metastasis. Factors of tumor consolidation diameter (p < 0.001) and preoperative serum carcinoembryonic antigen (CEA) level (p = 0.017) are independent risk factors lymph node metastasis in cN0 NSCLC. The ROC curve showed that the cut-off value of consolidation diameter was 16.5 mm, and the area under the curve (AUC) was 0.825 (p < 0.001, 95% CI 0.780-0.870); the cut-off value of serum CEA level was 1.765 mu g/L, and the AUC was 0.661 (p < 0.001, 95% CI: 0.568-0.754). Moreover, 8 of 461 patients with tumor parenchyma <= 16.5 mm had lymph node metastasis, and 36 of 189 patients with tumor parenchyma > 16.5 mm had lymph node metastasis. Conclusion Tumor consolidation diameter and preoperative serum CEA are independent factors to predict cN0 NSCLC with tumor size <= 30 mm. For patients with tumor parenchyma > 16.5 mm, the probability of lymph node metastasis is higher and lymph node dissection is recommended. For patients with tumor parenchyma <= 16.5 mm, the probability of lymph node metastasis is lower and lymph node sampling is feasible.

Background It is difficult to determine the lymph node metastasis of patients with early-stage non-small cell lung cancer (NSCLC) before surgery. The purpose of this study is to investigate risk factors of lymph node metastasis in early-stage NSCLC, thereby to identify the surgical indications for lymph node dissection in early-stage NSCLC. Methods We conducted a retrospective study of patients with tumor size ≤ 30mm who underwent radical resection of NSCLC. Binary logistic regression analysis was applied to predict risk factors for lymph node metastasis, and subject operating characteristics (ROC) curve was used to evaluate the independent risk factors. Results Overall, 44 patients (6.8%) with early-stage NSCLC had lymph node metastasis. Factors of tumor consolidation diameter (p < 0.001) and preoperative serum carcinoembryonic antigen (CEA) level (p = 0.017) are independent risk factors lymph node metastasis in early-stage NSCLC. The ROC curve showed that the cut-off value of consolidation diameter was 16.5mm, and the area under the curve (AUC) was 0.825 (p < 0.001, 95% CI: 0.780–0.870); the cut-off value of serum CEA level was 1.765µg/L, AUC = 0.661( p < 0.001, 95% CI: 0.568–0.754). Moreover, 8 of 461 patients with tumor parenchyma ≤ 16.5mm had lymph node metastasis, and 36 of 189 patients with tumor parenchyma > 16.5mm had lymph node metastasis. Conclusion Tumor consolidation diameter and preoperative serum CEA are independent factors to predict early stage NSCLC. For patients with tumor parenchyma > 16.5mm, the probability of lymph node metastasis is higher and lobectomy plus lymph node dissection is recommended. For patients with tumor parenchyma ≤ 16.5mm, the probability of lymph node metastasis is lower and sublobectomy plus lymph node sampling is feasible.