Background: DNA‐Dependent Protein Kinase Catalytic Subunit (PRKDC), a key component of the DNA damage repair pathway, is associated with chemotherapy resistance and tumor progression.Methods: Here we analyzed transcriptome data of ~2,000 breast cancer patients and performed functional studies in vitro to investigate the function of PRKDC in breast cancer.Results: Our results revealed overexpression of PRKDC in multiple breast cancer subtypes. Consistent with patients’ data, overexpression of PRKDC was also observed in breast cancer cell lines compared to normal breast epithelial cells. Knockdown of PRKDC in MCF‐7 and T47D breast cancer cell lines resulted in proliferation inhibition, reduced colony formation and G2/M cell cycle arrest. Furthermore, we showed that PRKDC knockdown induced proliferation inhibition through activation of p38 MAPK, but not ERK MAPK, signaling pathway in breast cancer cells. Blockage of p38 MAPK signaling could largely rescue proliferation inhibition and cell cycle arrest induced by PRKDC knockdown. Moreover, we analyzed gene expression and clinical data from six independent breast cancer cohorts containing ~1,000 patients. In all cohorts, our results consistently showed that high expression of PRKDC was significantly associated with poor survival in both treated and untreated breast cancer patients.Conclusion: Together, our results suggest that high expression of PRKDC facilitates breast cancer cell growth via regulation of p38 MAPK signaling, and is a prognostic marker for poor survival in breast cancer patients.

Telepathology (TP) provides remote pathology services for primary diagnosis practices, including intraoperative consultation of surgical pathology; it has not been widely implemented in China. In this study, the results of an implementation were reported, which lasted for two and a half years, and demonstrated the experience of the diagnosis of the intraoperative frozen sections by using TP consultation platform of Southern Medical University and Guangzhou Huayin Medical Laboratory Center (SMU-HUAYIN TP) in China. The SMU-HUAYIN TP consultation platform connects 71 participating basic hospitals and 11 senior pathologists. Nanfang Hospital is a high-level hospital located in a large city in China. This retrospective study summarizes the experience and results of TP for frozen section diagnosis by comparing the data of the platform and Nanfang Hospital over a period of 2.5 years from January 2015 to June 2017. A total of 5233 cases were submitted to the platform, including 1019 cases in 2015, 2320 cases in 2016, and 1894 cases in 2017. The most common cases were breast (30.42%), followed by thyroid (29.05%) and gynecological (24.86%). Average turn-around time (TAT) of the cases from the platform in 2015 and 2016 was controlled within 30 min. In most TP cases (90.31%) and cases from Nanfang Hospital (86.14%), a definitive diagnosis was provided. The coincidence rate was 99.77% in the TP cases and 99.35% in the cases from Nanfang Hospital. The false positive and false negative rates of TP cases were 0.04 and 0.19%, respectively and no significant difference was found among different senior pathologists (P = 0.974, P = 0.989, P > 0.05). Similarly, there was no significant difference between TP cases and cases from Nanfang Hospital that were diagnosed by the same senior pathologist (P > 0.05). Our results indicate that TP in frozen section diagnosis could improve patient care and solve the problem of unevenly distributed pathology resources in China. We believe that in the near future, TP in frozen section diagnosis will become an important component of telemedicine and will play a significant role in health care reform in China.

Purpose: Oncology studies employing digital dissection methodologies have provided some insight on the biological features of tumor microenvironment of Triple-negative breast cancer (TNBC), but molecular diagnostics rarely have therapeutic impact. We aimed to identify a novel prognostic biomarker to investigate immune characteristics of TNBC using transcriptomic features. Patients and Methods: We extracted whole transcriptome from breast cancer tissue of 30 TNBC patients and then used bioinformatics approaches to characterize the different immune cell contents in tumor tissue and para-cancerous tissue. We extract 2 indicators to describe the major differences in immune infiltration in the microenvironment between tumor tissue and para-cancerous tissue. We then combined the 2 indicators that represent the levels of increased and decreased infiltration in each sample to obtain the Immune Infiltration Score (IIS). Then we compared the tumor-infiltrating immune cell contents and immune infiltrating status in TNBC samples with CIBERSORT and ESTIMATE score to validate the IIS. Finally, 132 TNBC patients from the Cancer Genome Atlas program (TCGA) dataset was used to validate the predictive power of IIS. Results: 4 types of upregulated and 4 types of downregulated immune cells were identified in the tumor tissue samples of the TNBC patients. Then we developed a novel biomarker, IIS. Results showed that IIS score can clearly separate cancer and para-cancerous tissue. Using the same cutoff value of 0 in the TNBC-TCGA cohort, we show that those patients with a higher IIS had significantly higher PD-L1 expression and shorter progression-free survival time than those with a lower IIS value, indicating IIS score can be generalized to other TNBC datasets. Conclusion: we explored the immune infiltration landscape in 30 TNBC patients and provided IIS as a novel and reliable biomarker to evaluate the progression-free survival and prognosis of the TNBC patients.

Purpose: Our aim was to construct a signature that accurately predicted the prognostic and immune response of melanoma.Methods: First, the weighted co-expression network analysis (WGCNA) algorithm was used to identify the hub genes related to clinical phenotypes of melanoma in the cancer genome atlas (TCGA) database. Nest, the least absolute shrinkage and selection operator (LASSO) analysis was used to dimensionality reduction of these hub genes and constructed a prognostic signature to predict the prognosis and immunosuppressive response of melanoma.Result: Through in-depth analysis, we constructed a 5-mRNA prognostic signature and verified its prognostic value in internal (TCGA-SKCM, n = 452) and external independent datasets (GSE53118, n = 79). Based on this signature, the tumor immune microenvironment (TME) of melanoma was characterized, and the result was found that patients in the high-risk group had lower CD8 T cell infiltration and immune checkpoint expression (PD-1, PD-L1, CTLA4), as well as higher M0/M2 macrophage infiltration. Our results also found the risk score based on a 5-mRNA signature was significantly associated with tumor mutational burden (TMB) and tumor stem cell markers (CD20, CD38, ABCB5, CD44, etc.). Lastly, we built a nomogram for clinician prediction for the prognosis of patients with melanoma.Conclusion: Our findings indicated that the 5-mRNA signature has an important predictive value for the overall survival of melanoma. By analyzing the tumor immune microenvironment and tumor stem cell marker between different groups, a new method is provided for the stratified diagnosis and treatment of melanoma.

Introduction: In December 2019, a novel epidemic of coronavirus pneumonia (COVID-19) was reported，and population-based studies had shown that cancer was a risk factor for death from COVID-19 infection. However, the molecular mechanism between COVID-19 and cancer remains indistinct. In this paper, we analyzed the nucleic acid sensor (DDX58) of SARS-CoV-2 virus, which is a significant gene related to virus infection. For purpose of clarifying the characteristics of DDX58 expression in malignant tumors, this study began to systematically analyze the DDX58 expression profile in the entire cancer type spectrum.Methods: Using TCGA pan-cancer database and related data resources, we analyzed the expression, survival analysis, methylation expression, mutation status, microsatellite instability (MSI), immune related microenvironment, gene related network, function and drug sensitivity of DDX58.Results: The expression level of DDX58 mRNA in most cancers was higher than the expression level in normal tissues. Through TIMER algorithm mining, we found that DDX58 expression was closely related to various levels of immune infiltration in pan-cancer. The promoter methylation level of DDX58 was significantly increased in multiple cancers. In addition, abnormal expression of DDX58 was related to MSI and TMB in multiple cancers, and the most common type of genomic mutation was “mutation.” In the protein–protein interaction (PPI) network, we found that type I interferon, phagocytosis, ubiquitinase, and tumor pathways were significantly enriched. Finally, according to the expression of DDX58 indicated potential sensitive drugs such as Cediranib, VE−821, Itraconazole, JNJ−42756493, IWR−1, and Linsitinib.Discussion: In conclusion, we had gained new insights into how DDX58 might contribute to tumor development, and DDX58 could be used as an immune-related biomarker and as a potential immunotherapeutic target for COVID-19 infected cancer patients.