Autophagy, a highly conserved cellular proteolysis process, has been involved in non-small cell lung cancer (NSCLC). We tried to develop a prognostic prediction model for NSCLC patients based on the expression profiles of autophagy-associated genes. Univariate Cox regression analysis was used to determine autophagy-associated genes significantly correlated with overall survival (OS) of the TCGA lung cancer cohort. LASSO regression was performed to build multiple-gene prognostic signatures. We found that the 22-gene and 11-gene signatures could dichotomize patients with significantly different OS and independently predict the OS in TCGA lung adenocarcinoma (HR=2.801, 95% CI=2.252-3.486, P<0.001) and squamous cell carcinoma (HR=1.105, 95% CI=1.067-1.145, P<0.001), respectively. The prognostic performance of the 22-gene signature was validated in four GEO lung cancer cohorts. Moreover, GO, KEGG, and GSEA analyses unveiled several fundamental signaling pathways and cellular processes associated with the 22-gene signature in lung adenocarcinoma. We also constructed a clinical nomogram with a concordance index of 0.71 to predict the survival possibility of NSCLC patients by integrating clinical characteristics and the autophagy gene signature. The calibration curves substantiated fine concordance between nomogram prediction and actual observation. Overall, we constructed and verified a novel autophagy-associated gene signature that could improve the individualized outcome prediction in NSCLC.

Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/MBJOomBEfIE Background and Objectives: Esophageal squamous cell carcinoma (ESCC) remains one of the most common malignancies in China and has a high metastasis rate and poor prognosis. Fibroblast activation protein-α (FAP-α) is a serine peptidase the expression of which in cancer-associated fibroblasts has been associated with a higher risk of metastases and poor survival. This study aimed to analyze the correlation of FAP-α expression with the lymph node metastasis and prognostic significance in ESCC. Methods: FAP-α expression was examined in 121 resected ESCC specimens and 10 adjacent normal tissue using immunohistochemistry. FAP-α expression was scored in the stromal fibroblasts adjacent to neoplastic nests. A chi-square test was used to analyze the correlation between FAP-α expression in tumors stromal and lymph node metastasis of ESCC. The association between FAP-α expression and prognosis was evaluated using univariable and multivariable statistical modeling. Results: FAP-α expression was absent in the benign controls. FAP-α expression was evident in the stromal 37% (45/121) of ESCC. Expression of FAP-α level is significantly associated with lymph node metastasis (p=0.023), but it is not correlated to age, gender, and tumor location in ESCC patients. Stromal FAP-α expression was significantly associated with poor survival in univariable (HR 2.009; 95% CI 1.259-3.205; p=0.003) and multivariable analysis (HR 1.833; 95% CI 1.144-2.937; p=0.012). Conclusion: FAP-α may be an important regulator in lymph node metastasis of ESCC and may provide a novel therapeutic target in ESCC.

The present study was designed to investigate the expression of tumor-associated macrophages (TAMs) in gastric cancer and its clinicopathological relationship. In addition, we also aimed to analyze the relationship between helicobacter pylori (HP) infection and TAMs in gastric cancer. The protein expression of CD16 and CD163 in 90 gastric cancer tissues and 30 margin tissues was detected by immunohistochemistry. HP infection was detected in 90 gastric cancer tissues and 30 margin tissues by gram staining and immunohistochemistry. There was no clear correlation between CD16 macrophages and gastric cancer. The density of CD163 macrophages was not correlated with the general condition of tumor patients, but with tumor size, tumor differentiation, lymphatic metastasis, depth of invasion and TNM stage. Additionally, the infection rate of HP in gastric cancer tissues was significantly higher. In summary, TAMs are associated with tumor size, degree of differentiation, depth of invasion, lymph node metastasis and TNM stage, suggesting their critical role in the invasion and metastasis of gastric cancer.

Purpose Pyroptosis is a recently discovered highly inflammatory form of programmed cell death, during which the N-terminus of the cleaved Gasdermin protein family forms pores in the cell membrane, leading to cell disintegration and the release of certain intracellular factors, including caspase3, gasdermin E (GSDME), and high mobility group proteins (HMGB1), which trigger a series of secondary inflammatory reactions. Specifically, caspase3 can lyse GSDME and induce pyrolysis, while HMGB1 is released passively after cell membrane destruction. In this study, the roles of these proteins in lung cancer tissues as well as their clinical significance were investigated. Patients and Methods The expression levels of GSDME, caspase3, and HMGB1 proteins in lung cancer and paracancerous tissues were determined via immunohistochemical staining, and their relationship with the clinical stage, pathological grade, and survival prognosis of the patients was analyzed. Further, CD8 + T cell accumulation in the above-mentioned tissues was also determined, and differences between them with respect to CD8 + T cell distribution were also investigated. Furthermore, the relationships between CD8 + T cell abundance and the expression levels of the above-mentioned proteins were determined via statistical analyses. Results Lung cancer and paracancerous tissues showed significantly different GSDME, caspase3, and HMGB1 protein expression levels. GSDME expression level and the presence or absence of lymph node invasion were identified as prognostic indicators of survival in patients with lung cancer. Surprisingly, however, HMGB1, which showed a certain level of correlation with the presence or absence of lymph node metastasis, could not be used as a prognostic indicator of survival. Conclusion GSDME may be an important prognostic indicator of survival in patients with lung cancer. However, the effects of HMGB1 expression level and CD8 + T cell abundance on the prognosis of patients with lung cancer still need further investigation.