m
6A is one of the most common post-transcriptional modification of eukaryotic mRNA [
7]. The effect of m
6A in cancer is reflected in the regulation of cancer-related gene expression. m
6A affects the occurrence and development of cancer by enhancing or inhibiting the expression of oncogenes and tumor suppressor genes and plays different roles in different tumors and different pathways [
8]. In a recent study by Zhang et al. [
9], the importance of m
6A modified regulators in small cell lung cancer was illustrated, and a prognostic feature based on multicentric m
6A regulators was developed for limited-stage SCLC (LS-SCLC) patients. This study identified that there may be a large number of m
6A modifications in LS-SCLC, and its dysregulated expression may be involved in the occurrence and development of SCLC. Using LASSO Cox model, 5 significant candidates (
G3BP1,
METTL5,
ALKBH5,
IGF2BP3 and
RBM15B) among 22 m
6A regulators were selected and used to establish a m
6A score system. The authors report m
6A score was an independent prognostic predictor in LS-SCLC. One of the interesting findings is that the m
6A score is significantly associated with therapeutic response and clinical benefit in both patients receiving adjuvant chemotherapy (ACT) and anti-PD-1 immunotherapy. Patients with low scores received a greater survival benefit from ACT, exhibited more CD8+ T cell infiltration, and were more responsive to ICB.
In recent years, with the focus on the role of m
6A in cancer, increasing evidence suggest that m
6A regulators are promising prognostic biomarkers which help determine chemotherapy and immunotherapy resistance [
10]. The excellent work by Zhang et al. showed a new application of m
6A regulators in cancer treatment response. Although there may inevitably be some deviations in the analysis of this study, more prospective and reliable studies are needed. This study is the first systematic examination of the m
6A modification pattern in LS-SCLC to establish a comprehensive prognostic model of m
6A regulators. The large study cohort increases the reliability and robustness of the m
6A score model. Furthermore, the m
6A score model based on tissue samples to predict the benefit of chemotherapy and immunotherapy has potential clinical application in the treatment and clinical management of SCLC patients.