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Background:PRDM12 is a newly discovered gene responsible for congenital insensitivity to pain (CIP). Its clinical manifestations are various and not widely known.Methods: The clinical data of two infants diagnosed with CIP associated with PRDM12 mutation were collected. A literature review was performed, and the clinical characteristics of 20 cases diagnosed with a mutation of PRDM12 were summarized and analyzed.Results: Two patients had pain insensitivity, tongue and lip defects, and corneal ulcers. The genomic analysis results showed that variants of PRDM12 were detected in the two families. The case 1 patient carried heterozygous variations of c.682+1G > A and c.502C > T (p.R168C), which were inherited from her father and mother, respectively. We enrolled 22 patients diagnosed with CIP through a literature review together with our cases. There were 16 male (72.7%) and 6 female (27.3%) patients. The age of onset ranged from 6 months to 57 years. The prevalence of clinic manifestation was 14 cases with insensitivity to pain (63.6%), 19 cases with self-mutilation behaviors (86.4%), 11 cases with tongue and lip defects (50%), 5 cases with mid-facial lesions (22.7%), 6 cases with distal phalanx injury (27.3%), 11 cases of recurrent infection (50%), 3 cases (13.6%) with anhidrosis, and 5 cases (22.7%) with global developmental delay. The prevalence of ocular symptoms was 11 cases (50%) with reduced tear secretion, 6 cases (27.3%) with decreased corneal sensitivity, 7 cases (31.8%) with disappeared corneal reflexes, 5.5 cases (25%, 0.5 indicated a single eye) with corneal opacity, 5 cases (22.7%) with corneal ulceration, and 1 case (4.5%) with a corneal scar.Conclusion: The syndrome caused by PRDM12 mutation is a clinically distinct and diagnosable disease that requires joint multidisciplinary management to control the development of the disease and minimize the occurrence of complications.

Genetic variation has been shown to affect tumor growth and progression, and the temperature at different latitudes may promote the evolution of genetic variation. Geographical data with latitudinal information is of importance to understand the interplay between genetic variants and environmental influence, such as the temperature, in gastric cancer (GC). In this study, we classified the GC samples from The Cancer Genome Atlas database into two groups based on the latitudinal information of patients and found that GC samples with low-latitude had better clinical outcomes. Further analyses revealed significant differences in other clinical factors such as disease stage and grade between high and low latitudes GC samples. Then, we analyzed the genomic and transcriptomic differences between the two groups. Furthermore, we evaluated the activity score of metabolic pathways and infiltrating immune cells in GC samples with different latitudes using the single-sample gene set enrichment analysis algorithm. These results showed that GC samples at low-latitude had lower tumor mutation burden and subclones as well as higher DNA repair activities. Meanwhile, we found that most immune cells were associated with the prognosis of low-latitude GC patients. At last, we constructed and validated an immune-related prognostic model to evaluate the prognosis of GC samples at different latitudes. This study has provided a further understanding of the geographical contribution to GC at the multiomic level and may benefit the individualized treatment of GC patients at different latitudes.

Intra-tumoral heterogeneity (ITH) is a critical factor leading to aggressive progression and response to immunotherapy in lung adenocarcinoma (LUAD). However, the relationship between ITH and immune cells in the tumor microenvironment (TME) has not been systematically elucidated. In the present study, we evaluated the ITH status of LUAD samples based on the mutational data obtained from The Cancer Genome Atlas database. First, we identified five key immune pathways with a significantly continuous downtrend among normal, low-heterogeneous, and high-heterogeneous samples and further excavated nine key immune cells related to the key immune pathways and tumor heterogeneity. Then, two immune subtypes were defined by a consensus clustering algorithm based on the infiltration of these immune cells. Differences between these two immune subtypes were remarkable, including alterations of tumor mutation burden and DNA copy number variation at the genomic level, various metabolic pathways, and the different clinical outcome, which was also validated in two independent Gene Expression Omnibus datasets. The results revealed that ITH was significantly associated with prognosis and infiltrating immune cells in the TME. Our study provides novel insights in understanding the relationship between ITH and immune cells and contributes to the immunotherapy of LUAD patients.

Circular RNAs (circRNAs) play various roles in cellular functions. However, no studies have been reported on the potential involvement of circRNAs in the biosynthesis of secondary metabolites in plants. Here, we performed a genome-wide discovery of circRNAs from root, stem and leaf samples of Salvia miltiorrhiza using RNA-Seq. We predicted a total of 2,476 circRNAs with at least two junction reads using circRNA_finder and CIRI, of which 2,096, 151 and 229 were exonic, intronic and intergenic circRNAs, respectively. Sequence similarity analysis showed that 294 out of 2,476 circRNAs were conserved amongst multiple plants. Of the 55 predicted circRNAs, 31 (56%) were validated successfully by PCR and Sanger sequencing using convergent and divergent primer pairs. Alternative circularisation analysis showed that most parental genes produced two circRNAs. Functional enrichment analyses of the parental genes showed that the primary metabolism pathways were significantly enriched, particularly the carbon metabolism. Differential expression analysis showed that the expression profiles of circRNAs were tissue-specific. Co-expression analysis showed 275 circRNAs, and their parental genes had significantly positive correlations. However, 14 had significantly negative correlations. Weighted gene co-expression network analysis showed that nine circRNAs were co-expressed with four modules of protein-coding genes. Next, we found 416 exonic circRNAs with miRNA-binding sites, suggesting possible interactions between circRNAs and miRNAs. Lastly, we found six validated circRNAs, namely, SMscf2473-46693-46978, SMscf3091-29256-29724, SMscf16-111773-112193, SMscf432-13232-13866, SMscf7007-10563-10888 and SMscf1730-1749-2013, which were originated from the genes involved in the biosynthesis of secondary metabolites. Their parental genes were acetyl-CoA C-acetyltransferase 1 (SmAACT1), 1-deoxy-d-xylulose-5-phosphate synthase 2 (SmDXS2), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 1 (SmHDR1), kaurene synthase-like 2 (SmKSL2), DWF4 and CYP88A3, respectively. In particular, the correlation coefficient of SMscf2473-46693-46978 and SmDXS2 gene was 0.86 (p = 0.003), indicating a potential interaction between this pair of circRNA and its parent gene. Our results provided the first comprehensive catalogue of circRNAs in S. miltiorrhiza and identified one circRNA that might play important roles in the biosynthesis of secondary metabolites.

The aim of this study was to identify prognosis-related differentially expressed lncRNAs and mRNAs in chronic atrophic gastritis (CAG). By analysis of high-throughput whole-transcriptome sequencing data, the levels of lncRNAs and mRNAs between CAG and chronic non-atrophic gastritis were compared pairwisely. In total, 97,282 lncRNA transcripts and 20,307 mRNA transcripts were acquired, including 50 upregulated and 66 downregulated lncRNAs and 377 upregulated and 763 downregulated mRNAs in CAG (p < 0.05, fold change ≥ 2). Moreover, the interactions of the differentially expressed genes in CAG were investigated by gene ontology enrichment analysis, showing that the enriched genes are involved in many biological processes, such as MAP kinase activity, heat generation, and protein modification processes. Through the construction of co-expression networks of the differentially expressed genes in CAG, three critical lncRNAs nodes were identified as potential key factors in CAG. Eight mRNAs common in both the co-expression network and the protein–protein interaction network were selected via Venn analysis, including DGKA, EIF6, HKDC1, DHRS11, 1, KRT15, TESPA1, and CDHR2. Finally, the expression levels of five differentially expressed lncRNAs in CAG were confirmed by quantitative real-time polymerase chain reaction. In conclusion, this study presents novel promising biomarkers for the diagnosis of CAG.

Autophagy is a self-degradation process that maintains homeostasis against stress in cells. Autophagy dysfunction plays a central role in the development of tumors, such as colorectal cancer (CRC). In this study, autophagy-related differentially expressed genes, their downstream functions, and upstream regulatory factors including RNA-binding proteins (RBP) involved in programmed cell death in the CRC were investigated. Transcription factors (TFs) and miRNAs have been shown to mainly regulate autophagy genes. Interestingly, we found that some of the RBP in the CRC, such as DDX17, SETDB1, and POLR3A, play an important regulatory role in maintaining autophagy at a basal level during growth by acting as TFs that regulate autophagy. Promoter methylations showed negative regulations on differentially expressed autophagy gene (DEAG), while copy number variations revealed a positive role in them. A proportional hazards regression analysis indicated that using autophagy-related prognostic signature can divide patients into high-risk and low-risk groups. Autophagy associated FDA-approved drugs were studied by a prognostic network. This would contribute to the identifications of new potential molecular therapeutic targets for CRC.