Background: Targeted programmed cell death protein 1 (PD-1) therapy could effectively improve the long-term prognosis of patients with non-small cell lung cancer (NSCLC). The role of PD-1 targets in the progression of NSCLC has not been fully revealed. Methods:The differentially expressed genes (DEGs) in patients' blood after NSCLC treatment with PD-1 blocker nivolumab in the GSE141479 dataset were analyzed by GEO2R and identified in the TCGA database. The mechanism of action involved in the PD-1 target molecules via the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction (PPI) network shows the relationship between PD-1 target molecules. The factors affecting the prognosis of NSCLC patients were identified via the COX regression analysis and survival analysis to build the risk model and nomogram. Results: There were 64 DEGs in patients' blood after nivolumab treatment and 48 DEGs in NSCLC tissues. The PD-1 target molecules involved cell proliferation, DNA replication, cell cycle, lung cancer, and other cellular processes. The prognostic factors CCNA2, CHEK1, DLGAP5, E2F8, FOXM1, HIST1H2BH, HJURP, MKI67, PLK1, TPX2, and TYMS, and the independent factors HIST1H2BH and PLK1, influenced the prognosis of NSCLC patients. HIST1H2BH and PLK1 were overexpressed in LUAD and LUSC tissues. The elevated expression levels of HIST1H2BH and PLK1 were related to the overall survival (OS) and the progression-free survival of NSCLC patients. High-risk NSCLC patients had a poor prognosis and were an independent factor influencing the poor prognosis of NSCLC patients. The high-risk model group was enriched with signaling mechanisms such as cell cycle, DNA replication, and homologous recombination.Conclusions: The risk model based on PD-1 target molecules was helpful to assess the prognosis of NSCLC patients. HIST1H2BH and PLK1 might become prognostic biomarkers of NSCLC patients.

The present study used an in vitro model of cold cardioplegia in isolated working rat hearts to evaluate the possible role of ethyl pyruvate (EP) in promoting cardiac function and preventing apoptosis. Two groups of rats were evaluated; the EP (2 mM EP; n=8) and control (n=8) groups. Isolated rat hearts were perfused with Krebs-Henseleit buffer (KHB) for 30 min, arrested with cardioplegic solution and stored for 4 h in B21 solution at 4°C. The hearts were reperfused with KHB for 45 min. EP was added to the cardioplegic and storage solutions and also to KHB for reperfusion. Cardiac parameters of the heart rate, including left ventricular systolic pressure, left ventricular end-diastolic pressure, left ventricular developed pressure and maximal rise rate of the left ventricular pressure, were monitored. In addition, coronary flow, adenosine triphosphate (ATP) levels and malondialdehyde (MDA) content were recorded and apoptotic cell determination was detected. The functional parameters in the EP group were significantly higher compared with those in the control group during the reperfusion period (P<0.05). In addition, ATP levels were higher in the EP group than in the control group and the content of MDA was lower in the EP group than in the control group. A concentration of 2 mM EP significantly reduced the number of apoptotic cells in the EP group compared with that of the control group (P<0.05). Therefore, EP significantly preserved cardiac function, enhanced tissue ATP levels, attenuated myocardial oxidative injury and markedly reduced apoptosis following myocardial ischemia in an in vitro model of 4 h of cold cardioplegia and reperfusion.

Background/Aim: A great proportion of patients with rectal cancer initially present with locally advanced disease and can potentially benefit from neoadjuvant concurrent chemoradiotherapy (CCRT) for downstaging before surgery. However, risk and clinical outcome stratification remain a great challenge. We aimed to find the potential biomarker to predict the effect of neoadjuvant CCRT on rectal cancer. Methods: We identified epiregulin (EREG) as the most significant predictive marker for neoadjuvant CCRT response from the published rectal cancer transcriptome data set GSE35452. We collected 172 biopsy specimens from rectal cancer patients who received neoadjuvant CCRT followed by radical proctectomy, performed EREG immunohistochemistry, and analyzed the H-scores. We further examined the correlations between the expression level of EREG and clinicopathological features, tumor regression grade, and survival, including disease-specific survival (DSS), locoregional recurrence-free survival (LRFS), and metastasis-free survival (MeFS). Results: High EREG expression was significantly related to early pretreatment (pre-Tx) and posttreatment (post-Tx) tumor status (T1, T2, p = 0.047 and p < 0.001), pre-Tx and post-Tx negative nodal status (N0, p < 0.001 and p = 0.004), less vascular and perineurial invasion (p = 0.015 and p = 0.023), and higher tumor regression grade (p < 0.001). In the survival analysis, high EREG expression was significantly associated with better DSS (p < 0.0001), LRFS (p = 0.0004), and MeFS (p < 0.0001). In the multivariate analysis, high EREG expression remained prognostically significant for better DSS (p = 0.003; hazard ratio: 5.599). Conclusion: These data suggest that EREG is a potential predictive marker and therapeutic target in rectal cancer patients receiving neoadjuvant CCRT.

Background: In a data mining search for potential therapeutic targets to improve the outcome of rectal cancer, we identified PCSK1 as the cell-cell signaling gene most significantly associated with poor response to concurrent chemoradiotherapy (CCRT). This study aims to investigate the prognostic value of PCSK1 expression in rectal cancer patients who underwent neoadjuvant CCRT. Methods: Endoscopic biopsy specimens from 172 rectal cancer patients receiving neoadjuvant CCRT followed by curative surgery were assessed immunohistochemically for PCSK1 expression, and H-scores were determined. Expression levels of PCSK1 were further analyzed for correlations with clinicopathologic features, tumor regression grade, metastasis-free survival, disease-specific survival, and recurrence-free survival. Results: PCKS1 overexpression was significantly associated with pretreatment tumor status (T3-4; p = 0.009), pretreatment nodal status (N1-2; p < 0.001), posttreatment tumor status (T3-4; p < 0.001), posttreatment nodal status (N1-2; p < 0.001), vascular invasion (p = 0.003), and perineurial invasion (p = 0.023). PCKS1 overexpression was also found to be significantly associated with a lower degree of tumor regression (p < 0.001). In the univariate analysis, PCSK1 overexpression was significantly associated with lower disease-specific survival, metastasis-free survival, and recurrence-free survival (p < 0.005). PCSK1 overexpression remained an independent prognostic factor of lower disease-specific survival (p = 0.003; hazard ratio, 5.478) in the multivariate analysis. Conclusion: Determination of PCSK1 overexpression may be useful for identifying rectal cancer patients at risk for a poor response and worse survival after CCRT.