Objective: Tumor-associated macrophages (TAMs) deserve more focus because of its pivotal role in the development of solid tumors and they are related to poor outcomes of several tumors. However, the prognostic value of tumor-infiltrating TAMs in pancreatic cancer is still controversial. Experimental design: We conduct a meta-analysis of 1699 patients in 13 studies by reviewing the studies in which the authors evaluated the prognostic value of TAMs density in pancreatic cancer. These studies were searched from inception to November 2018. Hazard ratios (HR) with their corresponding 95% confidence intervals (95% CIs) were assessed to explore the prognostic significance of TAMs in pancreatic cancer. Besides, we also conducted a subgroup analysis and sensitivity analysis. Two reviewers independently abstracted data. Results: A total of 13 studies with 1699 patients were pooled in the analysis to evaluate prognostic value of TAMs in pancreatic cancer. The pooled HRs demonstrated CD68+ TAMs correlated with worse overall survival (OS) in pancreatic cancer patients (HR =1.41, 95% CI =1.05–1.90, random effects model, I^2,=82.5%, P=0.021). And high generalized M2-TAMs density was significantly associated with poor OS (HR =1.95, 95% CI =1.63–2.33, random effects model, I^2,=59.2%, P=0.000) and disease-free survival (HR =1.83, 95% CI =1.43–2.36, fixed effects model, I^2,=0.00%, P=0.000). Pooled analysis showed no significant correlation between elevated TAMs infiltration and lymph node metastasis, tumor stage, histological grade, sex, or tumor location. Conclusion: The density of TAMs has an impact on the overall survival of pancreatic cancer patients. M2-TAMs can be recognized as a prognostic indicator in pancreatic cancer, which may serve as a potential therapeutic target in the treatment of pancreatic cancer.

Solute carrier family 25 (SLC25) encodes transport proteins at the inner mitochondrial membrane and functions as carriers for metabolites. Although SLC25 genetic variants correlate with human metabolic diseases, their roles in colon cancer remain unknown. Cases of colon cancer were retrieved from The Cancer Genome Atlas, and the transcriptionally differentially expressed members (DEMs) of SLC25 were identified. DNA level alterations, clinicopathological characteristics, and clinical survival were also investigated. A risk score model based on the DEMs was constructed to further evaluate their prognostic values in a clinical setting. The results were preliminarily validated using bioinformatic analysis of datasets from the Gene Expression Omnibus, immunohistochemical evaluations in clinical specimens, and functional experiments in colon cancer-derived cell lines. Thirty-seven DEMs were identified among 53 members of SLC25. Eight of 37 DEMs were introduced into a risk score model using integrated LASSO regression and multivariate Cox regression. Validated by GSE395282 and GSE175356, DEMs with high-risk scores were associated with the phenotypes of increasing tumor immune infiltration and decreasing glycolysis and apoptosis contents. SLC25A5 was downregulated in cancer, and its upregulation was related to better overall survival in patients from public datasets and in clinical cases. High SLC25A5 expression was an independent prognostic factor for 79 patients after surgical treatment. A negative correlation between CD8 and SLC25A5 was determined in specimens from 106 patients with advanced colon cancer. SLC25A5 attenuated cell proliferation, upregulated the expression of programmed cell death-related signatures, and exerted its biological function by inhibiting the MAPK signaling pathway. Our study reveals that mitochondrial SLC25 has prognostic value in patients with colon cancer. The bioinformatic analyses by following verification in situ and in vitro provide direction for further functional and mechanistic studies on the identified member of SLC25.

Many patients with hepatocellular carcinoma (HCC) respond poorly to radiotherapy despite remarkable advances in treatment. A deeper insight into the mechanism of sensitivity of HCC to this therapy is urgently required. It is demonstrated that RECQL4 is upregulated in the malignant cells of patients with HCC. Elevated RECQL4 levels reduce the sensitivity of HCC to radiotherapy by repairing radiation‐induced double‐stranded DNA (dsDNA) fragments. Mechanistically, the inhibitory effect of RECQL4 on radiotherapy is due to the reduced recruitment of dendritic cells and CD8⁺ T cells in the tumor microenvironment (TME). RECQL4 disrupts the radiation‐induced transformation of the TME into a tumoricidal niche by inhibiting the cGAS‐STING pathway in dendritic cells. Knocking out STING in dendritic cells can block the impact of RECQL4 on HCC radiosensitivity. Notably, high RECQL4 expressions in HCC is significantly associated with poor prognosis in multiple independent cohorts. In conclusion, this study highlights how HCC‐derived RECQL4 disrupts cGAS‐STING pathway activation in dendritic cells through DNA repair, thus reducing the radiosensitivity of HCC. These findings provide new perspectives on the clinical treatment of HCC.

Alternative splicing (AS) has a critical role in tumor progression and prognosis. Our study aimed to investigate pancreatic cancer-specific AS events using RNA-seq data, gaining systematic insights into potential prognostic predictors. We downloaded 10,623 genes with 45,313 pancreatic cancer-specific AS events from the Cancer Genome Atlas (TCGA) and SpliceSeq database. Cox univariate analyses of overall survival suggested there was a remarkable association between 6,711 AS events and overall survival in pancreatic cancer patients (P < 0.05). The area under the curves (AUC) of the receiver operator characteristic curves (ROC) of risk score was 0.89 for final prognostic predictor. Results indicated that AS events of DAZAP1, RBM4, ESRP1, QKI, and SF1 were significantly associated with overall survival. The results of FunRich showed that transcription factors KLF7, GABPA, and SP1 were the most highly related to survival-associated AS genes. Furthermore, using DriverDBv2, we identified 13 driver genes associated with survival-associated AS events, including TP53 and CDC27. Thus, we concluded that the aberrant AS patterns in pancreatic cancer patients might serve as prognostic predictors.