The prognostic value of sialylation-related long non-coding RNAs in lung adenocarcinoma.

There has been increasing interest in the role of epigenetic modification in cancers recently. Among the various modifications, sialylation has emerged as a dominant subtype implicated in tumor progression, metastasis, immune evasion, and chemoresistance. The prognostic significance of sialylation-related molecules has been demonstrated in colorectal cancer. However, the potential roles and regulatory mechanisms of sialylation in lung adenocarcinoma (LUAD) have not been thoroughly investigated. Through Pearson correlation, univariate Cox hazards proportional regression, and random survival forest model analyses, we identified several prognostic long non-coding RNAs (lncRNAs) associated with aberrant sialylation and tumor progression, including LINC00857, LINC00968, LINC00663, and ITGA9-AS1. Based on the signatures of four lncRNAs, we classified patients into two clusters with different landscapes using a non-negative matrix factorization approach. Collectively, patients in Cluster 1 (C1) exhibited worse prognoses than those in Cluster 2 (C2), as well as heavier tumor mutation burden. Functional enrichment analysis showed the enrichment of several pro-tumor pathways in C1, differing from the upregulated Longevity and programmed cell death pathways in C2. Moreover, we profiled immune infiltration levels of important immune cell lineages in two subgroups using MCPcounter scores and single sample gene set enrichment analysis scores, revealing a relatively immunosuppressive microenvironment in C1. Risk analysis indicated that LINC00857 may serve as a pro-tumor regulator, while the other three lncRNAs may be protective contributors. Consistently, we observed upregulated LINC00857 in C1, whereas increased expressive levels of LINC00968, LINC00663, and ITGA9-AS1 were observed in C2. Finally, drug sensitivity analysis suggested that patients in the two groups may benefit from different therapeutic strategies, contributing to precise treatment in LUAD. By integrating multi-omics data, we identified four core sialylation-related lncRNAs and successfully established a prognostic model to distinguish patients with different characterizations. These findings may provide some insights into the underlying mechanism of sialylation, and offer a new stratification way as well as clinical guidance in LUAD.

Associations between pericarotid fat density and image-based risk characteristics of carotid plaque.

OBJECTIVES: In this study, we aimed to evaluate the associations between pericarotid fat density (PFD) and various risk characteristics of carotid plaque. METHODS: We retrospectively evaluated consecutive patients who were subjected to both high-resolution MRI and carotid artery CT angiography CTA at our institution between January 2016 and April 2021. The section of the carotid artery with the most severe lumen stenosis was selected from each patient for analysis. Two separated regions of interest (ROI) (each with an area of 2.5 mm2 and located at least 1 mm from the outer margin of the carotid artery wall) were defined in the perivascular fat tissue. The mean value of PFD (mean HU) was measured on the plaque side and the same axial non-plaque side. Then, the bilateral difference (D-value HU) was calculated (plaque side mean HU minus non-plaque side mean HU). According to carotid plaque risk characteristics (American Heart Association VI type [AHA VI], intraplaque hemorrhage [IPH], thinning and/or rupture of the fibrous cap [TRFC], lipid-rich necrotic core [LRNC], and calcification [CA]), the associations between PFD and five different risk characteristic subgroups were analyzed. The Student's t-test, Mann-Whitney U test, and Chi-square test were used to compare differences between different risk subgroups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive efficacy of PFD for carotid plaque risk characteristics. P < 0.05 was considered statistically significant. RESULTS: A total of 71 eligible patients (mean age 61.25 ± 10.35 years, 57 male) were examined in this study. For the plaque side and the non-plaque side, the mean PFD values were -36.25 ± 20.65 HU and -66.87 ± 15.00 HU, respectively. In the non-AHA VI and AHA VI subgroups, the values for the mean HU of the plaque side were -49.50 ± 20.53 and -33.55 ± 19.78, respectively (P = 0.014). The D-value HU was higher for the AHA VI group compared to the non-AHA VI group (33.61 ± 16.72 vs. 15.91 ± 14.52, respectively; P = 0.001). Compared to the non-IPH subgroup, the IPH subgroup had a higher mean HU value for the plaque side (-47.68 ± 18.26 vs. -29.63 ± 19.16, respectively; P < 0.001) and a higher D-value HU (17.80 ± 13.27 vs. 38.03 ± 15.46, respectively; P < 0.001). Compared to the low risk non-TRFC subgroup, the TRFC subgroup had a higher D-value HU (24.51 ± 16.16 vs. 33.55 ± 17.65, respectively; P = 0.042). The D-value of PFD was found to be a significant predictor of both AHA VI classification (AUC: 0.79; SE: 64.41%; SP: 83.33%; P = 0.0001) and IPH (AUC: 0.83; SE: 88.89%; SP: 65.38%; P < 0.0001). CONCLUSION: Our study found that PFD was significantly associated with high risk AHA VI plaque characterization, IPH, and TRFC. Therefore, PFD has the potential to be used as an indirect clinical marker of plaque instability.

Vaccination with FasL-/TCL plus MHSP65 induces improved anti-lung cancer immunity in mice.

In a previous study, we constructed a MHSP65-TCL anti-lung cancer vaccine with Lewis lung carcinoma TCL plus MHSP65, and illustrated its anti-lung cancer effect through specific and nonspecific anti-tumor immunity. However, TCL contains some immunoinhibit components such as FasL. If this component can be eliminated from TCL, the anti-tumor immunity of MHSP65-TCL constructed with TCL should be improved. In the present study, we knocked down FasL from Lewis lung carcinoma cells and prepared MHSP65-(FasL-/TCL) with this cell line's TCL. After further investigation, MHSP65-(FasL-/TCL) exhibited a better ability to reduce splenocytes apoptosis, promote its activation and secretion of secretingTNF-ß, IL-2 compared with MHSP65-(FasL+/TCL). Accordingly, specific and nonspecific antitumor immunity induced by MHSP65-(FasL-/TCL) is stronger than that of MHSP65-(FasL+/TCL). In vivo, MHSP65-(FasL-/TCL) immunization can prolong survival of Lewis lung carcinoma bearing mice. Thus, we report that the anti-lung cancer effect of MHSP65-TCL can be improved by removal of FasL from the TCL. It provides a new route to construct MHSP65-TCL and other antitumor vaccines based on TCL.