Development and Clinical Validation of a Novel 5 Gene Signature Based on Fatty Acid Metabolism-Related Genes in Oral Squamous Cell Carcinoma.

Background/Aim: Lipid metabolism disorders play a crucial role in tumor development and progression. The aim of the study focused on constructing a novel prognostic model of oral squamous cell carcinoma (OSCC) patients using fatty acid metabolism-related genes. Methods: Microarray test and data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed genes related to fatty acid metabolism. The quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of targeted fatty acid metabolism genes. A risk predictive scoring model of fatty acid metabolism-related genes was generated using a multivariate Cox model. The efficacy of this model was assessed by time-dependent receiver operating characteristic curve (ROC). Results: 14 fatty acid metabolism-related genes were identified by microarray test and TCGA database analysis and then confirmed by PCR. Finally, a 5 gene signature (ACACB, FABP3, PDK4, PPARG, and PLIN5) was constructed and a RiskScore was calculated for each patient. Compared to the high RiskScore group, the low RiskScore group had better overall survival (OS) (p = 0.02). The RiskScore derived from a 5 gene signature was a prognostic factor (HR: 3.73, 95% CI: 1.38, 10.09) for OSCC patients. The predictive classification efficiencies of RiskScore were evaluated and the area under the curve (AUC) values for 1, 3, and 5 years were 0.613, 0.652, and 0.681, respectively. Then we compared the predictive performance of the prognostic model with or without the RiskScore. The 5 gene-derived RiskScore can improve the predictive performance with AUC values of 0.760, 0.803, and 0.830 for 1, 3, and 5 years OS in prognostic model including the RiskScore. While the predicted AUC values of the model without RiskScore for 1, 3, and 5 years OS were 0.699, 0.715, and 0.714, respectively. Conclusion: We developed a predictive score model using 5 fatty acid metabolism-related genes, which could be a potential prognostic indicator in OSCC.

Mediation analysis of erythrocyte lipophilic index on the association between BMI and risk of oral cancer.

AIMS: To explore the relationship between the fatty acid lipophilic index (LI) of the erythrocyte membrane and oral cancer risk, as well as to evaluate the possibility of LI acting as a mediator of the association between body mass index (BMI) and oral cancer. METHOD: Twenty-three fatty acids (FAs) of the erythrocyte membrane were measured using gas chromatography in 380 patients with oral cancer and 387 control subjects. The LI was calculated based on the FA proportion and FA melting points. The association of BMI and erythrocyte LI with oral cancer risk was analysed using logistic regression. The mediation effect of LI on the association between BMI and oral cancer risk was evaluated using mediation analysis. RESULTS: Among the control group, 46.0% were overweight or obese, which was significantly higher than that of oral cancer patients (29.5%). Significant differences in erythrocyte membrane saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were observed between the patient and control groups. The proportion of C18:1 n-9 from the MUFA family increased in oral cancer patients (12.67%) compared with controls (12.21%). While the total proportion of n-3 PUFAs decreased in oral cancer patients compared with controls, with C20:5 n-3 decreasing from 0.66 to 0.47%, and C22:6 n-3 decreasing from 5.82 to 4.86%. The LI was lower in the control participants (M = 27.6, IQR: 27.3-27.9) than in the oral cancer patients (M = 28.2, IQR: 27.9-28.5). BMI was inversely associated with oral cancer risk with a fully adjusted OR of 0.59 (95% CI: 0.43-0.83), while LI was positively associated with oral cancer risk with a fully adjusted OR of 1.99 (95% CI:1.36-2.94). LI explained 7% of the variance in the relationship between BMI and oral cancer risk. CONCLUSIONS: The distribution of the FA profile in erythrocyte membranes differed between the oral cancer patients and the control group. The LI derived from the profile of FAs was positively associated with the risk of oral cancer, and the associations between BMI and oral cancer risk can be explained, at least in part, by LI.

The receptor-like cytoplasmic kinase CDG1 negatively regulates Arabidopsis pattern-triggered immunity and is involved in AvrRpm1-induced RIN4 phosphorylation.

Arabidopsis CDG1 negatively regulates flg22- and chitin-triggered immunity by promoting FLS2 and CERK1 degradation and is partially required for bacterial effector AvrRpm1-induced RIN4 phosphorylation. Negative regulators play indispensable roles in pattern-triggered immunity in plants by preventing sustained immunity impeding growth. Here, we report Arabidopsis thaliana CONSTITUTIVE DIFFERENTIAL GROWTH1 (CDG1), a receptor-like cytoplasmic kinase VII member, as a negative regulator of bacterial flagellin/flg22- and fungal chitin-triggered immunity. CDG1 can interact with the flg22 receptor FLAGELLIN SENSITIVE2 (FLS2) and chitin co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (CERK1). CDG1 overexpression impairs flg22 and chitin responses by promoting the degradation of FLS2 and CERK1. This process requires the kinase activity of MEK KINASE1 (MEKK1), but not the Plant U-Box (PUB) ubiquitin E3 ligases PUB12 and PUB13. Interestingly, the Pseudomonas syringae effector AvrRpm1 can induce CDG1 to interact with its host target RPM1-INTERACTING PROTEIN4 (RIN4), which depends on the ADP-ribosyl transferase activity of AvrRpm1. CDG1 is capable of phosphorylating RIN4 in vitro at multiple sites including Thr166 and the AvrRpm1-induced Thr166 phosphorylation of RIN4 is diminished in cdg1 null plants. Accordingly, CDG1 knockout attenuates AvrRpm1-induced hypersensitive response and increases the growth of AvrRpm1-secreting bacteria in plants. Unexpectedly, AvrRpm1 can also induce FLS2 depletion, which is fully dependent on RIN4 and partially dependent on CDG1, but does not require the kinase activity of MEKK1. Collectively, this study reveals previously unknown functions of CDG1 in both pattern-triggered immunity and effector-triggered susceptibility in plants.