ABSTRACT. Epigenetic inactivation of Ras-associated domain family 1A (RASSF1A) by hyper-methylation of its promoter region has been identified in various cancers. However, the role of RASSF1A in renal cancer has neither been thoroughly investigated nor reviewed. In this study, we reviewed and performed a meta-analysis of 13 published studies reporting correlations between methylation frequency of the RASSF1A promoter region and renal cancer risk. The odds ratios (ORs) of eligible studies and their corresponding 95% confidence intervals (95%CIs) were used to correlate RASSF1A promoter methylation with renal cell cancer risk and clinical or pathological variables, respectively. RASSF1A promoter methylation was significantly associated with the risk of renal cell cancer (OR = 19.35, 95%CI = 9.57-39.13). RASSF1A promoter methylation was significantly associated with pathological tumor grade (OR = 3.32, 95%CI = 1.55-7.12), and a possible positive correlation between RASSF1A promoter methylation status and tumor stage was noted (OR = 1.89, 95%CI = 1.00-3.56, P = 0.051). Overall, this meta-analysis demonstrated that RASSF1A promoter methylation is significantly associated with increased risk of renal cell cancer. RASSF1A promoter methylation frequency was positively correlated with pathological tumor grade, but not the clinical stage. This study showed that RASSF1A promoter methylation could be utilized to predict renal cell cancer prognosis.

Pulmonary fibrosis is an interstitial lung disease that can be caused by various factors. Here, we first observed extensive IgA deposition in the extracellular matrix (ECM) of the lungs of mice with pulmonary fibrosis induced by silica inhalation. Consistent with this phenomenon, spatial transcriptomic sequencing of fresh mouse lung tissues from control mice and model mice showed that Igha transcripts were highly expressed in the lesion area. Single-cell RNA sequencing (scRNA-seq) and reconstruction of B cell receptor (BCR) sequences revealed a new cluster of cells with a shared BCR and high expression of genes related to immunoglobulin IgA production. Surprisingly, these clonal cells had more characteristics of AT2 (alveolar epithelial cell type 2) cells than B cells; thus, these cells were named AT2-like cells. Therefore, we propose that secretion of IgA into the ECM by AT2-like cells is an important process that occurs during lung fibrosis.

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