Integrated single-cell and bulk RNA-Seq analysis enhances prognostic accuracy of PD-1/PD-L1 immunotherapy response in lung adenocarcinoma through necroptotic anoikis gene signatures.

In addition to presenting significant diagnostic and treatment challenges, lung adenocarcinoma (LUAD) is the most common form of lung cancer. Using scRNA-Seq and bulk RNA-Seq data, we identify three genes referred to as HMR, FAM83A, and KRT6A these genes are related to necroptotic anoikis-related gene expression. Initial validation, conducted on the GSE50081 dataset, demonstrated the model's ability to categorize LUAD patients into high-risk and low-risk groups with significant survival differences. This model was further applied to predict responses to PD-1/PD-L1 blockade therapies, utilizing the IMvigor210 and GSE78220 cohorts, and showed strong correlation with patient outcomes, highlighting its potential in personalized immunotherapy. Further, LUAD cell lines were analyzed using quantitative PCR (qPCR) and Western blot analysis to confirm their expression levels, further corroborating the model's relevance in LUAD pathophysiology. The mutation landscape of these genes was also explored, revealing their broad implication in various cancer types through a pan-cancer analysis. The study also delved into molecular subclustering, revealing distinct expression profiles and associations with different survival outcomes, emphasizing the model's utility in precision oncology. Moreover, the diversity of immune cell infiltration, analyzed in relation to the necroptotic anoikis signature, suggested significant implications for immune evasion mechanisms in LUAD. While the findings present a promising stride towards personalized LUAD treatment, especially in immunotherapy, limitations such as the retrospective nature of the datasets and the need for larger sample sizes are acknowledged. Prospective clinical trials and further experimental research are essential to validate these findings and enhance the clinical applicability of our prognostic model.

Association of the lncRNA-GAS5 promoter region rs145204276 polymorphism with sevoflurane maintenance anesthesia outcomes on patients undergoing laparoscopic cholecystectomy.

OBJECTIVES: To further investigate how sevoflurane affects the oxidative stress injury (OSI) in patients undergoing laparoscopic cholecystectomy (LC). METHODS: A prospective cohort study was carried out at Shandong Provincial Third Hospital, Jinan, China on 82 gallstone patients who underwent LC, with sevoflurane maintenance during surgery. Genotyping analysis of the rs145204276 polymorphism was performed using the TaqMan platform. Oxidative stress injury and liver injury parameters were also examined. Lipopolysaccharide (LPS)-induced macrophages, which were challenged with sevoflurane, propofol, or the lncRNA-GAS5 overexpressing plasmid, were used to evaluate the effect of Sevoflurane on lncRNA-GAS5-mediated macrophage polarization. RESULTS: At TM1 and TM2, the levels of OSI markers and long noncoding (lnc) RNA-GAS5 were not obviously different, whereas at the TM3 time point, these indices were significantly different between the Del-Sevoflurane and Del-Propofol subgroups. These indices were not different between the Ins-sevoflurane and Ins-Propofol subgroups at any time point. Cell-based experiments demonstrated that Sevoflurane could increased the lncRNA-GAS5 level in LPS-induced Del-macrophages (p=0.0058), but Propofol did not have this effect (p=0.847). Both Sevoflurane and Propofol did not have the effect on lncRNA-GAS5 level in LPS-induced Ins-macrophages (p=0.321 and p=0.822, respectively). CONCLUSION: Sevoflurane maintenance can decrease OSI during LC in the Del genotype of the rs145204276 polymorphism. The Del genotype facilitates lncRNA-GAS5 up-regulation under Sevoflurane exposure and therefore decrease the extent of M1 macrophage polarization.

LncRNA-GAS5 and its Promoter Region Polymorphism Associate with Helper Th17 Polarization and Predict Postoperative Pain and the Prognosis of the Patients with Hepatocellular Carcinoma Undergoing Hepatectomy.

BACKGROUND: The relationship between genetic polymorphism and postoperative pain and the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is not fully understood. OBJECTIVE: To examine whether lncRNA-GAS5 and its promoter region rs145204276 polymorphism can predict postoperative pain and prognosis of the patients with HCC undergoing hepatectomy. METHODS: Seventy patients with HCC undergoing hepatectomy were enrolled. The lncRNA-GAS5 levels in CD4+ T cells from peripheral blood mononuclear cells (PBMC-CD4+ T cells) and tumor tissues were measured by qRT-PCR. Genotyping analysis of rs145204276 was performed using the TaqMan platform. PBMC-CD4+ T cells were isolated and the cytokine levels in helper T (Th) cells were determined by flow cytometry. Patients with Ins/Ins genotype carrying the rs145204276 polymorphism were allocated into the Ins group, and others were allocated into the Del group. RESULTS: The lncRNA-GAS5 level decreased significantly in PBMC-CD4+ T cells and tumor tissues compared with the healthy controls and corresponding adjacent non-tumor tissues. The patients with Del/Del genotype showed significantly higher lncRNA-GAS5 expression in PBMC-CD4+ T cells, lower postoperative pain scores, and better overall survival. LncRNA-GAS5 expression in PBMC-CD4+ T cells was negatively associated with IL-6, IL-17, and the RORγT/CD3 ratio (an indicator of Th17 polarization). CONCLUSION: LncRNA-GAS5 expression and its promoter region rs145204276 polymorphism are prognostic biomarkers that can predict postoperative pain of patients with HCC undergoing hepatectomy.