Combining single-cell and bulk RNA sequencing, NK cell marker genes reveal a prognostic and immune status in pancreatic ductal adenocarcinoma.

The NK cell is an important component of the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC), also plays a significant role in PDAC development. This study aimed to explore the relationship between NK cell marker genes and prognosis, immune response of PDAC patients. By scRNA-seq data, we found the proportion of NK cells were significantly downregulated in PDAC and 373 NK cell marker genes were screened out. By TCGA database, we enrolled 7 NK cell marker genes to construct the signature for predicting prognosis in PDAC patients. Cox analysis identified the signature as an independent factor for pancreatic cancer. Subsequently, the predictive power of signature was validated by 6 GEO datasets and had an excellent evaluation. Our analysis of relationship between the signature and patients' immune status revealed that the signature has a strong correlation with immunocyte infiltration, inflammatory reaction, immune checkpoint inhibitors (ICIs) response. The NK cell marker genes are closely related to the prognosis and immune capacity of PDAC patients, and they have potential value as a therapeutic target.

CDC23 knockdown suppresses the proliferation, migration and invasion of liver cancer via the EMT process.

Liver cancer (LC) is a malignant tumour that is associated with high mortality rates worldwide. Cell division cycle 23 (CDC23) acts as an oncogene in papillary thyroid cancer. In addition, epithelial-mesenchymal transition (EMT) is frequently involved in the malignant metastasis of various cancer types. Therefore, we hypothesized that CDC23 may regulate the malignant biological behaviours of LC cells through EMT. Proliferation, colony formation and Transwell assays, western blotting and xenograft experiments were performed. The results of the present study showed that CDC23 was highly expressed in LC cell lines. In addition, it was found via multiple in vitro assays that CDC23 knockdown reduced the proliferation, migration and invasion of LC cell lines. Finally, an in vivo study confirmed that CDC23 knockdown inhibited the growth of xenograft LC in nude mice. More importantly, the changes in the levels of EMT-related marker proteins were analysed in the sh-CDC23 group compared with the sh-NC group of cells and xenografts. E-cadherin was upregulated, and N-cadherin and vimentin were significantly downregulated after CDC23 silencing. Taken together, these results revealed that the knockdown of CDC23 inhibits the progression of LC by regulating EMT and that CDC23 may be a novel therapeutic target for LC.

Comparison of oncologic outcomes between pancreaticoduodenectomy and total pancreatectomy for pancreatic adenocarcinoma.

BACKGROUND: Pancreatoduodenectomy (PD) and total pancreatectomy (TP) are two surgical methods to treat patients with pancreatic head adenocarcinoma (PHAC). However, the oncologic outcomes of TP for PHAC remain controversial. In this study, we compared early mortality and long-term survival patients undergoing TP and those with PD. METHODS: All patients diagnosed with non-metastatic PHAC who underwent PD or TP from 1988 to 2016 were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to balance the inter-group covariates. Cancer-specific survival (CSS) was the primary endpoint. RESULTS: A total of 4748 patients (743 TP and 4005 PD) were included in the study. Some 740 patients who underwent TP were matched with 1479 who had PD. After PSM, there was no difference between TP and PD groups regarding 30-day mortality (3.5% vs. 2.7%, p = 0.290) and 90-day mortality (9.9% vs. 8%, p = 0.135). More importantly, TP showed comparable survival in comparison to PD, prior or after excluding patients who died within 30 and 90 days. Besides, multivariate analysis revealed that tumor size, tumor stage, N stage, chemotherapy, and radiation were significant prognostic factors. CONCLUSION: PD and TP have similar early mortality and long-term survival for patients with PHAC. In selected patients, TP can be used when oncologically appropriate.

Curculigoside mitigates hepatic ischemia/reperfusion-induced oxidative stress, inflammation, and apoptosis via activation of the Nrf-2/HO-1 pathway.

Curculigoside has been shown to decrease oxidative stress and inflammatory reactions in many disorders, but its effects during hepatic ischemia-reperfusion injury (IRI) remain unknown. This research aims to determine the protective role and the potential mechanism of action of curculigoside in hepatic IRI. Here, a well-established rat model of partial warm IRI was constructed; serum ALT/AST and H&E staining were employed to assay the extent of liver injury; the superoxide dismutase, malondialdehyde, IL-6, and TNF-α contents were determined using the corresponding kits; the apoptosis index was evaluated by TUNEL staining; and the expression of Nrf-2, HO-1, and apoptosis-associated proteins was detected by qRT-PCR and Western blotting. The results showed that curculigoside pretreatment effectively mitigated hepatic IRI, as demonstrated by decreases in the levels of serum aminotransferases, hepatocellular necrosis and apoptosis, oxidative stress markers, infiltration of inflammatory cells, and secretion of proinflammatory cytokines. Mechanistically, the expression of Nrf-2 and HO-1 was greatly suppressed by hepatic IRI and reactivated by curculigoside. Furthermore, cotreatment with ML-385, an inhibitor of Nrf-2, counteracted the protective effect of curculigoside against hepatic IRI. The results of our study show that curculigoside plays a protective role in hepatic IRI by inhibiting oxidative stress, inflammation, and apoptosis and that its effects may be associated with activation of the Nrf-2/HO-1 pathway.

Observation Versus Resection for Small, Localized, and Nonfunctional Pancreatic Neuroendocrine Tumors: A Propensity Score Matching Study.

OBJECTIVES: The best treatment modalities for small (1-2 cm), localized, and nonfunctional pancreatic neuroendocrine tumors remain controversial. Therefore, we aimed to evaluate whether surgical resection provides survival benefit over observation in those patients. METHODS: From 1973 to 2015, all eligible patients were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching (1:2) method was performed. The primary endpoints evaluated were overall survival (OS) and cancer-specific survival (CSS). RESULTS: We identified 681 patients, of which 122 and 559 patients received observation and resection, respectively. Propensity score-matched patients who underwent surgery (n = 183) had significantly improved OS (P = 0.008) compared with matched patients who underwent observation (n = 106), but there was no difference in CSS (P = 0.310). On multivariate analysis, resection could improve OS but not CSS. Besides, poorly differentiated/undifferentiated tumor had a worse OS and CSS. Subgroup analysis showed that patients 60 years and older who underwent resection could achieve a longer OS and CSS. CONCLUSIONS: This disease exhibits a very good prognosis. Patients undergoing resection were associated with comparable 5-year CSS but longer 5-year OS compared with those receiving observation. Elderly patients (≥60) may obtain benefit from surgery, whereas the treatment of younger patients should be individualized.