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Jie Wu,1,2,* Yu-Chen Wang,1,2,* Wen-Hao Xu,1,2,* Wen-Jie Luo,1,2 Fang-Ning Wan,1,2 Hai-Liang Zhang,1,2 Ding-Wei Ye,1,2 Yuan-Yuan Qu,1,2 Yi-Ping Zhu1,2 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ding-Wei Ye; Yi-Ping ZhuDepartment of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong an Road, Shanghai 200032, People’s Republic of ChinaTel +86– 21– 64175590Fax +86– 21– 64438640Email fudanzhuyiping@163.com; dwyeli@yahoo.com.cnIntroduction: The cell-surface ectonucleotidase CD39 is a key molecule of the immunosuppressive adenosine pathway within the tumor microenvironment. However, the relationship between CD39 and clear cell renal cell carcinoma (ccRCC) is rarely reported and still remains unclear.Methods: CD39 expression was first analyzed using the Oncomine and the Tumor IMmune Estimation Resource (TIMER) databases, and then examined in ccRCC patients (n=367) who had undergone radical nephrectomy using immunohistochemistry (IHC) and real-time quantitative PCR analysis (qPCR). The prognosis value of CD39 in ccRCC was evaluated by Cox proportional hazards analysis. Functional and gene set enrichment analysis (GSEA) was performed using transcriptomic data of ccRCC from TCGA. Correlation analysis between CD39 and tumor-infiltrating lymphocytes (TILs) was performed using the TISIDB database. The impact of CD39 on immune checkpoint therapy (ICT) was evaluated by two public cohorts.Results: CD39 mRNA and protein expression was upregulated in tumor tissues from ccRCC patients and aberrant expression of CD39 was associated with advanced tumor stage and poor prognosis in ccRCC patients. EMT, IL-2/STAT5, inflammatory response, interferon gamma and KRAS hallmark gene sets were identified as CD39-related signaling pathway. The expression level of CD39 was significantly and positively correlated with high abundance of the regulatory TILs including NK cells, macrophages, Th cells and Treg cells. CD39 was correlated with expression of several immune checkpoints and higher CD39 expression was associated with better OS of ccRCC patients who received ICT.Conclusion: CD39 is a powerful prognostic marker of ccRCC patients. Increased tumor expression of CD39 mRNA is significantly correlated with infiltrating levels of TILs, and better efficacy of ICT to ccRCC. CD39 could be a novel therapeutic target for ccRCC.Keywords: renal cell carcinoma, CD39, prognosis, TCGA, infiltrating immune cells, immune checkpoint therapy

Additional file 2. Supplementary Table 1. Distribution of prognostic risk factors in 57 renal eAML patient. Risk factors included: pT3 and pT4, presence of necrosis, mitotic count≥2; the presence of atypical mitoses; severe nuclear atypia, SMA negative, Ki-67≥10%. Low-risk group: including 0-1 risk factor, Intermediate-risk group: including 2-3 risk factors, High-risk group: including 4-7 risk factors. *p value less than 0.05 was considered as statistically significant and marked in bold.

Additional file 1. Supplementary Figure 1. Correlation between clinical parameters and prognosis. Survival curves indicated the PFS (A) and OS (B) of total cohort. Patients with tumour size>7cm were significantly correlated with PFS (C) (HR=4.47, p=0.0061), but not significant in OS (D) (HR=4.61, p=0.053). Patients with pT3-pT4 stage were correlated with both shorter PFS (E) (HR=3.74, p=0.0044) and OS (F) (HR=10.27, p=0.0022). Patients with presence of atypical mitosis (G, H), presence of necrosis (I, J), severe nuclear atypia (K, L), and mitotic count >=2 (M, N) were significantly correlated with poor PFS (presence of atypical mitoses: HR=5.41, p=2: HR=7.56, p

Patients with clear cell renal cell carcinoma (ccRCC) typically face aggressive disease progression when metastasis occurs. Here, we screened and identified differentially expressed genes in three microarray datasets from the Gene Expression Omnibus database. We identified 112 differentially expressed genes with functional enrichment as candidate prognostic biomarkers. Lasso Cox regression suggested 10 significant oncogenic hub genes involved in earlier recurrence and poor prognosis of ccRCC. Receiver operating characteristic curves validated the specificity and sensitivity of the Cox regression penalty used to predict prognosis. The area under the curve indexes of the integrated genes scores were 0.758 and 0.772 for overall and disease-free survival, respectively. The prognostic values of ADAMTS9, C1S, DPYSL3, H2AFX, MINA, PLOD2, RUNX1, SLC19A1, TPX2, and TRIB3 were validated through an analysis of 10 hub genes in 380 patients with ccRCC from a real-world cohort. The expression levels of were of high prognostic value for predicting metastatic potential. These findings will likely significantly contribute to our understanding of the underlying mechanisms of ccRCC, which will enhance efforts to optimize therapy.

Additional file 3: Table S1. Clinicopathological characteristics baseline in relation to AQP9 expression status in TCGA cohort. Table S2. Univariate Cox logistic regression analysis of PFS in TCGA and FUSCC cohort (PFS: progression-free survival; TCGA: the Cancer Genome Atlas; FUSCC: Fudan university shanghai cancer center). Table S3. Univariate Cox logistic regression analysis of OS in TCGA and FUSCC cohort (OS: overall survival; TCGA: the Cancer Genome Atlas; FUSCC: Fudan university shanghai cancer center). Table S4. Correlation analysis between AQP9 and immune cell infiltrations in ccRCC samples using TIMER.

The goal of the present work is to reduce the number of the training samples used in our color prediction model based on CIEXYZ using an Effective Coverage Map while keeping satisfying prediction. A general approach is proposed in this paper to choose the best reference combination for the training samples. The approach is based on the dot gain behavior of each primary ink, which is characterized by three curves using CIEXYZ tri-stimulus values. The proposed approach is built in our model to predict the color values for the color prints using two different devices, i.e. a laser printer and an inkjet printer. For the laser printer the number of the training samples is reduced from 125 to 64 while still giving quite good result. The approach also shows that for the test laser printer it is possible to further cut this number to 53 with a satisfying result. For the inkjet printer the number of training samples for our model is reduced from 125 to 79 or 64, both giving satisfying results.

This paper describes a method for 3-D surface estimation based on reflection measurements in different orientationsof the light source and the paper. To facilitate the estimation, surface facets that probably support specular reflection weremarked and isolated, so as to enable the application of sample Lambertian reflectance model over those non-specular reflectionpoints. A computer controlled imaging device was used to capture images in a large number of orientations. The image capturewas performed using several different exposures in order to present larger dynamic irradiance range. Images together with theircounterpoints under antithetical illuminations were used to deal with the possible situation that light failed illumination arrivalson some points locate behind bulges.Iteration using difference approximation as well as enforcing integrability algorithm wereused to calculate the surface height based on Shaping from Shading algorithm.