Dysregulated intratumoral immune reactions are shaped by complex networks of cytokines, which coordinate with tumor cells to determine tumor progression and aggressiveness. In lung adenocarcinoma (LUAD), the role of intratumoral cytokine gene expression for stratifying prognosis has not been systematically investigated. Using high-dimensional datasets of cancer specimens from clinical patients in The Cancer Genome Atlas (TCGA), we explored the transcript abundance and prognostic impact of 27 clinically evaluable cytokines in 500 LUAD tumor samples according to clinicopathological features and two common driver mutations (EGFR and KRAS). We found that reduced expression of IL12B presented as the single prognostic factor for both poor overall survival (OS) and recurrence free survival (RFS) with high hazard ratios. Moreover, we identified that elevated expression of IL6, CXCL8 and CSF3 were additional independent predictors of poor RFS in LUAD patients. Their prognostic significance was further strengthened by their ability to stratify within clinicopathological factors. Notably, we prioritized high risk cytokines for patients with or without mutations in EGFR and KRAS. Our results provide integrative associations of cytokine gene expression with patient survival and tumor recurrence and demonstrate the necessity and validity of relating clinicopathological and genetic disposition factors for precise and personalized disease prognosis.

To investigate the association between tumor protein 53 polymorphism and esophageal cancer cases using systematic review and meta-analysis, this provides a basis for future researches. All studies on tumor protein 53 mutations in patients with esophageal cancer and its influencing factors, which published before May 2021, were collected by searching Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure and Wanfang data. Meta-analysis was performed using RevMan 5.3. Ten eligible studies (Chinese n=7, English n=3) involving 1379 cases were included in this analysis. Meta-analysis showed that the odds ratio value (95 % confidence interval) of tumor protein 53 mutations in Caucasian patients with esophageal cancer was 70.51 (9.77, 508.88), z=4.22, p<0.0001; the odds ratio value (95 % confidence interval) of tumor protein 53 mutations in Chinese Han patients with esophageal cancer was 1.06 (0.63, 1.79), z=0.22, p=0.83; the odds ratio value (95 % confidence interval) of tumor protein 53 mutations in Chinese Uyghur patients with esophageal cancer was 18.48 (4.44, 76.90), z=4.01, p<0.0001. The odds ratio value (95 % confidence interval) of tumor protein 53 mutations in patients with esophageal cancer was 1.01 (0.60, 1.72), z=0.05, p=0.96; the odds ratio value (95 % confidence interval) of tumor protein 53 deletions in patients with esophageal cancer was 23.02 (9.04, 58.63), z=6.57, p≤0.00001. There was no significant difference in tumor protein 53 mutations between patients with esophageal cancer and the control group. There is a certain correlation between tumor protein 53 polymorphism and the incidence of esophageal cancer and the change of tumor protein 53 gene will affect the risk and prognosis of esophageal cancer.

IntroductionHepatocellular carcinoma (HCC) is one of the most invasive cancers with a low 5-year survival rate. Pyroptosis, a specialized form of cell death, has shown its association with cancer progression. However, its role in the prognosis of HCC has not been fully understood.MethodsIn our study, clinical information and mRNA expression for 1076 patients with HCC were obtained from the five public cohorts. Pyroptotic clusters were generated by unsupervised clustering based on 40 pyroptosis-related genes (PRGs) in the TCGA and ICGC cohort. A pyroptosis-related signature was constructed using least absolute shrinkage and selection operator (LASSO) regression according to differentially expressed genes (DEGs) of pyroptotic clusters. The signature was then tested in the validation cohorts (GES10142 and GSE14520) and subsequently validated in the CPTAC cohort (n=159) at both mRNA and protein levels. Response to sorafenib was explored in GSE109211.ResultsThree clusters were identified based on the 40 PRGs in the TCGA cohort. A total of 24 genes were selected based on DEGs of the above three pyroptotic clusters to construct the pyroptotic risk score. Patients with the high-risk score showed shorter overall survival (OS) compared to those with the low-risk score in the training set (P&lt;0.001; HR, 3.06; 95% CI, 2.22-4.24) and the test set (P=0.008; HR, 1.61; 95% CI, 1.13-2.28). The predictive ability of the risk score was further confirmed in the CPTAC cohort at both mRNAs (P&lt;0.001; HR, 2.99; 95% CI, 1.67-5.36) and protein levels (P&lt;0.001; HR, 2.97; 95% CI 1.66-5.31). The expression of the model genes was correlated with immune cell infiltration, angiogenesis-related genes, and sensitivity to antiangiogenic therapy (P&lt;0.05).DiscussionIn conclusion, we established a prognostic signature of 24 genes based on pyroptosis clusters for HCC patients, providing insight into the risk stratification of HCC.

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