Period2 is associated with immune cell infiltration and is a potential diagnostic and prognostic marker for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) health challenge worldwide. Many studies showed that circadian rhythms play a critical role in tumor development. This study aimed to investigate the role of the circadian gene period2 (PER2) in HCC development and explore the possible mechanisms involved. Methods: From fresh HCC tissues and paired paracancerous tissues, we measured PER2 mRNA and protein expression levels and calculated the correlations between PER2 expression and clinicopathological parameters in patients with HCC. We used transcriptome data from The Cancer Genome Atlas to mine the PER2 gene, including single gene difference analysis, single gene co-expression analysis, gene set enrichment analysis, immune infiltration analysis, and methylation analysis to explore its role and mechanism in HCC occurrence and development. Results: PER2 expression levels were significantly lower in HCC tissues than in the paired paracancerous tissues. PER2 expression in HCC significantly correlated with neural invasion, Child-Pugh classification, and China liver cancer staging stage in HCC patients. The differentially expressed genes associated with PER2 were significantly enriched in mitochondrial oxidative phosphorylation, transcriptional translation, amino acid metabolism, and other related pathways. PER2 expression levels significantly correlated with immune cell infiltration and immune checkpoint genes and positively correlated with TP53 expression in HCC tissues. The DNA methylation status in eight CpG islands of the PER2 gene was associated with HCC outcomes. Conclusion: PER2 is a potential diagnostic and prognostic biomarker and a promising therapeutic target in HCC.

Data-independent acquisition (DIA) mass spectrometry reveals related proteins involved in the occurrence of early intestinal-type gastric cancer.

Identifying proteins associated with the onset of early intestinal-type gastric cancer (EIGC) can yield valuable insights into the pathogenesis of this specific subtype of gastric cancer. Data-independent acquisition mass spectroscopy (DIA-MS) was utilized to identify the differential protein between 10 cases of EIGC and atrophic gastritis with intestinal metaplasia (NGC). The expressions of IPO4, TBL1XR1, p62/SQSTM1, PKP3, and CRTAP were verified by immunohistochemistry (IHC) in 20 EIGC samples, 17 gastric low-grade intraepithelial neoplasia (LGIN) samples, and 21 healthy controls. The prognostic values of the five genes were validated in the transcriptome data by survival analysis. A total of 4,028 proteins were identified using DIA-MS and a total of 177 differential proteins were screened with log2(fold change) > 1.5. Among them, 113 proteins were significantly up-regulated, and 64 proteins were significantly down-regulated in EIGC tissues. IHC results showed that proteins IPO4, TBL1XR1, p62/SQSTM1, PKP3, and CRTAP were highly expressed in the cytoplasm of EIGC and LGIN, which was consistent with the results of DIA-MS. Among them, p62/SQSTM1 may undergo nuclear-cytoplasmic transfer. The five protein-coding genes were associated with intestinal-type gastric cancer survival and exhibited differential expression across various disease stages. The study successfully identified differentially expressed proteins between EIGC and NGC, providing potential biomarkers and valuable insights into the mechanism underlying intestinal-type gastric cancer.

Is Peroral Endoscopic Myotomy a Potential Therapy for Esophageal Absent Contractility?

AIM: Peroral endoscopic myotomy (POEM) is recommended for the endoscopic treatment of achalasia and esophageal junction outflow obstruction (EGJOO); however, absent contractility, a subtype of peristalsis disorders classified by the Chicago Classification of esophageal motility v3.0, has no effective treatment. The purpose of this study was to assess the efficacy of POEM in absent contractility, in the part of the patients presents with dysphagia. METHODS: We conducted a single-center retrospective study at a tertiary referral center. We included 30 patients who mainly complain with dysphagia, and they underwent POEM from January 2013 to December 2018. The data of high-resolution esophageal manometry was collected before and after POEM. They were divided into 3 groups: EGJOO, Achalasia, and Absent contractility according to the Chicago Classification of esophageal motility v3.0 before POEM. Telephone follow-up was made in February 2019 to obtain Eckardt scores and weight changes. RESULTS: We found that both Eckardt scores and integrated relaxation pressure decreased post-POEM in the 3 groups (P<0.05). Eckardt score was significantly lower in the EGJOO group than in the Absent contractility group (P=0.004) post-POEM. The difference of Eckardt Score was higher in the EGJOO group (P=0.010) and the Achalasia group (P=0.007) than in the Absent contractility group, as was weight gain (P=0.023; P=0.002). CONCLUSIONS: These findings suggest that POEM is an effective endoscopic procedure for patients with EGJOO and achalasia. Furthermore, POEM can significantly improve symptoms in patients with absent contractility, although less so than for the other 2 groups. POEM is a potential therapy for absent contractility patients presenting with dysphagia.