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Abstract. The family of semaphorins has been demonstrated to possess tumor suppressor activity, in which semaphorin 3B (SEMA3B) is differentially expressed in several types of tumors. The relationship between SEMA3B expression and its clinical significance in gastric cancer (GC) is currently unclear. In the present study, the expression and methylation status of the SEMA3B gene were detected by quantitative PCR and bisulfite sequencing PCR (BSP). Data indicated that the levels of SEMA3B mRNA decreased in gastric tumor tissues and the methylation status of SEMA3B in the tumor group was higher than the paired normal tissues. By BSP, the SEMA3B gene showed high methylated status which was detected in all 4 cell lines (AGS, BGC-823, MGC-803 and SGC-7901). Treatment of the cells with 5-Aza-2'-deoxycytidine revealed clearly elevated mRNA levels of SEMA3B. These results were further confirmed by western blot analysis of Sema3b protein expression. At the same time, increased expression of p53 mRNA in BGC-823, MGC-803 was detected and indicated that p53 may be involved in the regulation of SEMA3B expression in specific genetic background. Downregulation of SEMA3B was negatively correlated with tumor size and N staging in GC (P<0.05). In conclusion, CpG methylation of SEMA3B epigenetically regulates SEMA3B expression during development of GC. Furthermore, 5-Aza-2'-deoxycytidine could reverse the hypermethylation status of SEMA3B, which may benefit future studies exploring the application of demethylating agents in clinical usage of GC.

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Background: CD8 + T cell in pancreatic ductal adenocarcinoma (PDAC) is closely related to the prognosis and treatment response of patients. Accurate preoperative CD8 + T-cell expression can better identify the population benefitting from immunotherapy. Purpose: To develop and validate a machine learning classifier based on noncontrast magnetic resonance imaging (MRI) for the preoperative prediction of CD8 + T-cell expression in patients with PDAC. Study Type: Retrospective cohort study. Population: Overall, 114 patients with PDAC undergoing MR scan and surgical resection; 97 and 47 patients in the training and validation cohorts. Field Strength/Sequence/3 T: Breath-hold single-shot fast-spin echo T2-weighted sequence and noncontrast T1-weighted fat-suppressed sequences. Assessment: CD8 + T-cell expression was quantified using immunohistochemistry. For each patient, 2232 radiomics features were extracted from noncontrast T1-and T2-weighted images and reduced using the Wilcoxon rank-sum test and least absolute shrinkage and selection operator method. Linear discriminative analysis was used to construct radiomics and mixed models. Model performance was determined by its discriminative ability, calibration, and clinical utility. Statistical Tests: Kaplan-Meier estimates, Student's t-test, the Kruskal-Wallis H test, and the chi-square test, receiver operating characteristic curve, and decision curve analysis. Results: A log-rank test showed that the survival duration in the CD8-high group (25.51 months) was significantly longer than that in the CD8-low group (22.92 months). The mixed model included all MRI characteristics and 13 selected radiomics features, and the area under the curve (AUC) was 0.89 (95% confidence interval [CI], 0.77-0.92) and 0.69 (95% CI, 0.53-0.82) in the training and validation cohorts. The radiomics model included 13 radiomics features, which showed good discrimination in the training cohort (AUC, 0.85; 95% CI, 0.77-0.92) and the validation cohort (AUC, 0.76; 95% CI, 0.61-0.87). Data Conclusions: This study developed a noncontrast MRI-based radiomics model that can preoperatively determine CD8 + T-cell expression in patients with PDAC and potentially immunotherapy planning.