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Tumor-associated macrophages (TAMs) regulate tumor immunity. Previous studies have shown that the programmed cell death protein 1 (PD-1)-positive TAMs have an M2 macrophage phenotype. CD68 is a biomarker of TAMs and is considered to be a poor prognostic marker of several malignancies. Our results show that PD-1-positive TAMs can be a negative survival indicator in patients with muscle-invasive bladder cancer (MIBC), and that the mechanistic effects could result due to a combination of PD-1 and CD68 activity. We analyzed 22 immune cell types using data from 402 patients with MIBC from the TCGA database, and found that a high immune score and M2 TAMs were strongly associated with poor clinical outcomes in patients with MIBC. Further, we analyzed resected samples from 120 patients with MIBC and found that individuals with PD-1-positive TAMs showed a reduction in 5-year overall survival and disease-free survival. Additionally, PD-1-positive TAMs showed a significant association with higher programmed death-ligand 1 (PD-L1) expression, the Ki67 index, the pT stage and fewer CD8-positive T cells. Through the co-immunoprecipitation (co-IP) assay of THP-1 derived macrophages, we found that CD68 can bind to PD-1. The binding of CD68 and PD-1 can induce M2 polarization of THP-1 derived macrophages and promote cancer growth. The anti-CD68 treatment combined with peripheral blood mononuclear cells (PBMC) showed obvious synergy effects on inhibiting the proliferation of T24 cells. Together, these results indicate for the first time that CD68/PD-1 may be a novel target for the prognosis of patients with MIBC.

Colorectal cancer (CRC) is one of the most malignant cancers, and its incidence is still steadily increasing. The DDX RNA helicase family members have been found to play a role in various cancers; however, the role of DDX54 in colorectal cancer is still unclear and needed to be defined. Here, we found DDX54 was overexpressed in CRC tissues by the label-free mass spectrum, which was also verified in tissue microarray of colon cancer, as well as the CRC cell lines and TCGA database. High DDX54 level was correlated with tumor stage and distant metastasis, which always indicated a poor prognosis to the CRC patients. DDX54 could promote the proliferation and mobility of CRC cells through increasing the phosphorylation level p65 and AKT leading to the tumorigenesis. Here, we have preliminarily studied the function of DDX54 in CRC, which would improve our understanding of the underlying biology of CRC and provide the new insight that could be translated into novel therapeutic approaches.

Summary The KIT11 mutation is the most frequent mutation pattern in gastrointestinal stromal tumors (GISTs). However, few studies have investigated the correlation between the KIT11-mutated grading system and imatinib mesylate (IM) sensitivity (the first choice for adjuvant treatment of GISTs). Here, we elucidated the clinical value of the KIT11-mutated grading system for prognostic prediction in patients with GISTs treated with IM. A total of 106 patients with GIST were treated with IM (8: intermediate-risk, 98: high-risk; 10: KIT9-mutated, 86: KIT11-mutated, 5: wild-type, and 5: other mutations). KIT11-mutated patients were divided into 3 grades based on the KIT11-mutated site and type. Clinical backgrounds and prognostic outcomes were retrospectively compared between the 3 groups. Of 86 KIT11-mutated patients treated with IM, 32 (37.21%) had grade 1 tumors, 37 (43.02%) had grade 2 tumors, and 17 (19.77%) had grade 3 tumors. The 5-year disease-free survival (DFS) was significantly worse in patients with grade 3 KIT11-mutated GISTs (41.96%, p = 0.001) than in those with grade 1 (93%) and grade 2 (70.64%) cases. The multivariable analysis suggested that the KIT11-mutated grading system was an independent risk factor for DFS in patients treated with IM (hazard risk, 2.512; 95% confidence interval, 1.370–4.607; p = 0.003). In conclusion, the KIT11-mutated grading system provides good prognostic stratification for DFS in patients treated with IM. Grade 1 tumors predict a favorable response to IM.

Background L. decemlineata is an exotic invasive insect pest, and invaded in Xinjiang Uygur autonomous region in China in the 1990s from Kazakhstan. It is a notorious defoliator of potato throughout most of the northern Xinjiang in current, and often causes extremely large yield losses of potato. Results The expression stability of nine L. decemlineata house-keeping genes (Actin, ACT1 and ACT2; ADP-ribosylation factor, ARF1 and ARF4; TATA box binding protein, TBP1 and TBP2; ribosomal protein RP4 and RP18; translation elongation factor 1α EF1α) was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in seven developmental stages, three larval tissues and two insecticide treatments. The results were analyzed using three software programs: geNorm, NormFinder and BestKeeper. Although there was no consistent ranking observed among the house-keeping genes across the samples, the overall analysis revealed that RP18, RP4, ARF1, and ARF4 were the four most stable house-keeping genes. In contrast, ACT1 and ACT2, two of the most widely used reference genes, had the least stability. Our results suggest that the combined use of the four most stably expressed genes may produce optimal normalization for qRT-PCR. Conclusions The expression stability of the house-keeping genes varies among different developing stages, in different tissues and under different experimental conditions. Our results will enable a more accurate and reliable normalization of qRT-PCR data in L. decemlineata.

Dystrophin and its associated proteins form a scaffold underneath the cardiomyocyte membrane and connect the intracellular cytoskeleton to the extracellular matrix. Dystrophin localizes at the X chromosome, whose mutations might result in Duchenne muscular dystrophy, Becker muscular dystrophy and X-linked dilated cardiomyopathy. In addition to these genetic dilated cardiomyopathies, some acquired dilated cardiomyopathy like viral dilated cardiomyopathy is also related to dystrophin disruption or aberrant cleavage. In this review, we summarize the structure and distribution of dystrophin and researches of dystrophin in genetic and viral dilated cardiomyopathy. Moreover, we hypothesize that dystrophin play a critical role in ventricular remodeling in ischemic myocardium and treatment targeting restoration of dystrophin onto membrane could benefit for ischemic cardiomyopathy.