Osteosarcoma is the most common malignant bone tumor in children and adolescence. Multiple immune-related genes have been reported in different cancers. The aim is to identify an immune-related gene signature for the prospective evaluation of prognosis for osteosarcoma patients. In this study, we evaluated the infiltration of immune cells in 101 osteosarcoma patients downloaded from TARGET using the ssGSEA to the RNA-sequencing of these patients, thus, high immune cell infiltration cluster, middle immune cell infiltration cluster and low immune cell infiltration cluster were generated. On the foundation of high immune cell infiltration cluster vs. low immune cell infiltration cluster and normal vs. osteosarcoma, we found 108 common differentially expressed genes which were sequentially submitted to univariate Cox and LASSO regression analysis. Furthermore, GSEA indicated some pathways with notable enrichment in the high- and low-immune cell infiltration cluster that may be helpful in understanding the potential mechanisms. Finally, we identified seven immune-related genes as prognostic signature for osteosarcoma. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression further confirmed that the seven immune-related genes signature was an innovative and significant prognostic factor independent of clinical features. These results of this study offer a means to predict the prognosis and survival of osteosarcoma patients with uncovered seven-gene signature as potential biomarkers.

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Identification and Verification of Immune-Related Gene Prognostic Signature Based on ssGSEA for Osteosarcoma.

The endoplasmic reticulum is responsible for much of a cell's protein synthesis and folding, but it also has an important role in sensing cellular stress. Recently, it has been shown that the endoplasmic reticulum mediates a specific set of intracellular signalling pathways in response to the accumulation of unfolded or misfolded proteins, and these pathways are collectively known as the unfolded-protein response. New observations suggest that the unfolded-protein response can initiate inflammation, and the coupling of these responses in specialized cells and tissues is now thought to be fundamental in the pathogenesis of inflammatory diseases. The knowledge gained from this emerging field will aid in the development of therapies for modulating cellular stress and inflammation.

From endoplasmic reticulum stress to the inflammatory response.

Initially identified as a T lymphocyte-elicited inhibitor of macrophage motility, macrophage migration inhibitory factor (MIF) has since been found to be expressed by nearly every immune cell type examined and overexpressed in most solid and hematogenous malignant cancers. It is localized to both extracellular and intracellular compartments and physically interacts with more than a dozen different cell surface and intracellular proteins. Although classically associated with and characterized as a mediator of pro-inflammatory innate immune responses, more recent studies demonstrate that, in malignant disease settings, MIF contributes to anti-inflammatory, immune evasive, and immune tolerant phenotypes in both innate and adaptive immune cell types. This review will summarize the studies describing MIF in tumor-specific innate and adaptive immune responses and attempt to reconcile these various pleiotropic functions in normal physiology.

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MIF-Dependent Control of Tumor Immunity.

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Benchmarking weakly-supervised deep learning pipelines for whole slide classification in computational pathology

Abstract Exosomes are well-known key mediators of intercellular communication and contribute to various physiological and pathological processes. Their biogenesis involves four key steps, including cargo sorting, MVB formation and maturation, transport of MVBs, and MVB fusion with the plasma membrane. Each process is modulated through the competition or coordination of multiple mechanisms, whereby diverse repertoires of molecular cargos are sorted into distinct subpopulations of exosomes, resulting in the high heterogeneity of exosomes. Intriguingly, cancer cells exploit various strategies, such as aberrant gene expression, posttranslational modifications, and altered signaling pathways, to regulate the biogenesis, composition, and eventually functions of exosomes to promote cancer progression. Therefore, exosome biogenesis-targeted therapy is being actively explored. In this review, we systematically summarize recent progress in understanding the machinery of exosome biogenesis and how it is regulated in the context of cancer. In particular, we highlight pharmacological targeting of exosome biogenesis as a promising cancer therapeutic strategy. 

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Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer

Background Recently, researchers have tried to predict patient prognosis using biomarker expression in cancer patients. The aim of this study was to develop a nomogram predicting the 5-year recurrence-free probability (RFP) of gastric cancer patients using prognostic biomarker gene expression. Methods We enrolled 360 patients in the training data set to develop the predictive model and nomogram. We analyzed the patients’ general variables and the gene expression levels of 10 prognostic biomarker candidates between the nonrecurrence and recurrence groups. We also performed external validation using 420 patients from the validation data set. Results The final nomogram was composed of age, sex, and the expression levels of CAPZA, PPase, OCT-1, PRDX4, gamma-enolase, and c-Myc. The five-year RFPs were 89%, 75%, 54% and 32% for the patients in the low-risk, intermediate-risk, high-risk and very-high-risk groups in the development cohort, respectively. In the external validation cohort, the 5-year RFPs were 89%, 75%, 63% and 60%, respectively. The areas under the curve were 0.718 (95% CI, 0.65–0.78) and 0.640 (95% CI, 0.57–0.70) for the training and validation data sets, respectively. The RFP Kaplan-Meier curves were significantly different among the 4 groups in the training and validation data sets (p  Conclusion This newly developed nomogram using gene expression can predict the 5-year RFP for gastric cancer patients after surgical treatment. We hope that this nomogram will help in the therapeutic decision between endoscopic treatment and gastrectomy.

Nomogram for predicting gastric cancer recurrence using biomarker gene expression.

Deep-Hipo: Multi-scale receptive field deep learning for histopathological image analysis.

BACKGROUND Rab27A and Rab27B are the major components of vesicle fusion and trafficking in exosome secretion and play important roles in tumor progression and metastasis. In addition, Rab27A and Rab27B are associated with tumor prognosis. This study investigated the prognostic roles of Rab27A and Rab27B expression in patients with non-small cell lung cancer (NSCLC). METHODS Rab27A and Rab27B expression was assessed in 133 cases of NSCLC by immunohistochemistry. We evaluated the correlations between Rab27A and Rab27B expression and clinicopathological data and determined their prognostic role in NSCLC. RESULTS Rab27A and Rab27B expression were significantly related to patient gender (P = 0.007 and 0.002, respectively) and histologic type (P = 0.009 and < 0.001, respectively), but not to patient age, smoking history, surgical method, or tumor node metastasis stage. The multivariate Cox proportional hazards regression model verified that high Rab27B expression is a prognostic factor for unfavorable disease-specific survival (hazard ratio 2.680, 95% confidence interval 1.116-6.437; P = 0.027) in squamous cell carcinoma (SQCC). Kaplan-Meier analysis revealed significantly poorer prognosis in SQCC patients with high Rab27B expression compared to patients with low Rab27B expression (P = 0.030). CONCLUSION High Rab27B expression could be an unfavorable prognostic factor in patients with SQCC of the lung.

Prognostic role of Rab27A and Rab27B expression in patients with non‐small cell lung carcinoma

Rab27 is an essential molecule of vesicle fusion and trafficking in exosome secretion process, which plays important roles in cancer progression and metastasis. Recent studies reported that Rab27 expression is also associated with cancer prognosis. Therefore, we performed a meta-analysis to reveal the prognostic significance of Rab27 expression in solid cancer. Data were extracted by searching on PubMed, Embase and Cochrane library until February 15 2020. Pooled hazard ratio (HR) with confidence interval (CI) was calculated to evaluate the association between Rab27 expression and survival in solid cancer. Ten studies with 1434 cancer patients were including for this meta-analysis. High expression of Rab27 was associated with poor survival (HR 2.67, 95% CI 1.52–4.69, p = 0.001). High expression of Rab27A was significantly associated with lymph node metastasis (HR 1.53, 95% CI 1.00–2.34, p = 0.048). High expression of Rab27B was significantly correlated with lymph node and distant metastasis (HR 2.15, 95% CI 1.56–2.95, p < 0.001; HR 6.80, 95% CI 3.12–14.85, p < 0.001), and higher TNM stage (HR 2.55, 95% CI 1.78–3.65, p < 0.001). This meta-analysis revealed that Rab27 expression could be a potential prognostic marker in solid cancer.

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Prognostic significance of Rab27 expression in solid cancer: a systematic review and meta-analysis.

Background Apolipoprotein E (APOE) modulates lipid homeostasis in the systemic circulation and induces inflammatory immune responses in the tumor microenvironment. We evaluated APOE expression in order to assess tumor progression in non-small cell lung cancer (NSCLC). Methods Immunohistochemical staining for APOE was performed on tissue microarray blocks from 148 patients who had undergone surgery for NSCLC. The staining intensity and the proportion of APOE-positive tumor cells (based on distinct membranous and cytoplasmic staining) were scored. The relationships between APOE expression and clinical (age, sex, and smoking history) and pathological (TNM stage and histological type) factors were evaluated. Results Positive APOE staining was observed in 93 (64.6%) patients. APOE expression patterns differed among NSCLC histological types (p-value = 0.016). Negative APOE expression was significantly associated with lymph node metastasis in NSCLC (p-value = 0.040). Both cases of N2 (stage IIIA) disease showed negative APOE expression. Conclusions APOE is a useful marker for assessing NSCLC patients with lymph node metastasis.

Hyun Min Koh

Papers

Nomogram for predicting gastric cancer recurrence using biomarker gene expression.

Deep-Hipo: Multi-scale receptive field deep learning for histopathological image analysis.

Prognostic role of Rab27A and Rab27B expression in patients with non‐small cell lung carcinoma

Prognostic significance of Rab27 expression in solid cancer: a systematic review and meta-analysis.

Apolipoprotein E is a predictive marker for assessing non-small cell lung cancer patients with lymph node metastasis