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Due to the existence of tumor molecular heterogeneity, even patients having similar clinicopathological features could have vastly different survival rates. Hence, we aimed to explore novel metabolism‐associated genes (MAGs) related molecular subtypes for clear cell renal cell carcinoma (ccRCC) and their immune landscapes for predicting prognosis and immune responses. Gene matrices and clinical information were downloaded from TCGA and ICGC datasets. Consensus clustering was conducted by the R "ConsensusClusterPlus" package. ccRCC patients were successfully divided into three clusters (MC1, MC2, and MC3) based on MAGs in both TCGA and ICGC datasets. Our established three MAGs were significantly associated with chemokine/chemokine receptor, IFN, CYT, angiogenesis, immune checkpoint molecules, tumor‐infiltrating immune cells, oncogenic pathways, pan‐cancer immune subtypes, and tumor microenvironment (TME) scores or expressions. Moreover, these three metabolic ccRCC subtypes could predict immunotherapeutic responses. We further constructed a characteristic index (LDAscore) in three metabolic ccRCC subtypes and identified LDAscore‐related modules by WGCNA. After deep data mining, 10 hub genes were obtained and seven genes (ATRX, BPTF, DHX9, EP300, POLR2B, SIN3A, UBE3A) were finally validated by qRT‐PCR. Our results successfully established a novel ccRCC subtype based on MAGs, providing novel insights into metabolism‐related ccRCC tumor heterogeneity and facilitating individualized therapy for future work. [ABSTRACT FROM AUTHOR]

Presents information on a study which determined the nonlinear properties of epitaxial lithium tantalate thin films. Experimental procedure; Results and discussion; Conclusion.

Purpose: DNA repair genes are potential biomarkers for chemotherapy in muscle-invasive bladder cancer (MIBC). O-methylguanine methyltransferase (MGMT) is involved in DNA repair and is found to affect the efficacy of platinum-based chemotherapy. However, the prognostic or predictive value of MGMT expression in chemotherapy for MIBC is unknown. Materials and Methods: Immunohistochemical staining for MGMT was performed in paraffin-embedded tumor tissue of high-grade MIBC patients who underwent cystectomy in two independent cohorts [ n = 74 for Fudan University Shanghai Cancer Center (FUSCC) cohort and n = 115 for Zhongshan Hospital (ZS) cohort]. MGMT messenger RNA (mRNA) analysis was conducted using patients' clinical and fragments per kilobase of exon model per million mapped fragments mRNA data from The Cancer Genome Atlas (TCGA) database ( n = 245). Results: In our cohorts, high MGMT expression was significantly correlated with shorter overall survival (OS) in patients with platinum-based adjuvant chemotherapy [hazard ratio (HR) 2.386, p = 0.048; HR 2.920, p = 0.007; HR 2.324, p = 0.004, respectively, in FUSCC, ZS, and combination sets], but not in patients without chemotherapy. These findings were corroborated by the TCGA set (HR 1.952 and 0.697 for patients with and without chemotherapy, respectively). The chemotherapy-MGMT interaction for OS was significant in both the surgery set ( p = 0.045) and TCGA set ( p = 0.034). Conclusions: We demonstrated that high MGMT expression is an independent poor prognostic factor in MIBC patients with platinum-based adjuvant chemotherapy, but not in patients without chemotherapy. MGMT expression may be a potential predictor for administration of adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

On the basis of aberrant interleukin-8 (IL-8) expression, a crucial angiogenesis factor and potential therapeutic target, in clear-cell renal cell carcinoma (ccRCC), this study aims to assess the prognostic significance of IL-8 in ccRCC. This retrospective study enrolled 271 patients who underwent nephrectomy for ccRCC in a single institution. The associations of IL-8 expression with clinical and pathological features were assessed using chi-squared tests. The impact on cancer-specific survival (CSS) and relapse-free survival (RFS) was analyzed using univariable and multivariable Cox regression models. The area under the receiver operating characteristic (ROC) curve (AUC) was used as an index of prognostic performance. Intratumoral IL-8 was found to be significantly elevated in ccRCC tissues compared with peritumor tissue and be predominately localized in the cytoplasm. Moreover, high IL-8 expression was positively correlated with Fuhrman grade ( P < 0.001). Multivariate Cox regression analysis identified IL-8 as an independent adverse prognostic factor of CSS ( P < 0.001) and RFS ( P < 0.001), which could be incorporated into the traditional TNM staging system to improve the prognostic value for CSS and RFS in ccRCC patients. The predictive accuracy of traditional TNM stage model was significantly improved when IL-8 expression was added. Increased expression of IL-8 is a potential independent adverse prognostic biomarker for CSS and RFS in patients with ccRCC after nephrectomy. [ABSTRACT FROM AUTHOR]

Purpose: DNA repair genes are potential biomarkers for chemotherapy in muscle-invasive bladder cancer (MIBC). O 6 -methylguanine methyltransferase (MGMT) is involved in DNA repair and is found to affect the efficacy of platinum-based chemotherapy. However, the prognostic or predictive value of MGMT expression in chemotherapy for MIBC is unknown., Materials and Methods: Immunohistochemical staining for MGMT was performed in paraffin-embedded tumor tissue of high-grade MIBC patients who underwent cystectomy in two independent cohorts [n = 74 for Fudan University Shanghai Cancer Center (FUSCC) cohort and n = 115 for Zhongshan Hospital (ZS) cohort]. MGMT messenger RNA (mRNA) analysis was conducted using patients' clinical and fragments per kilobase of exon model per million mapped fragments mRNA data from The Cancer Genome Atlas (TCGA) database (n = 245)., Results: In our cohorts, high MGMT expression was significantly correlated with shorter overall survival (OS) in patients with platinum-based adjuvant chemotherapy [hazard ratio (HR) 2.386, p = 0.048; HR 2.920, p = 0.007; HR 2.324, p = 0.004, respectively, in FUSCC, ZS, and combination sets], but not in patients without chemotherapy. These findings were corroborated by the TCGA set (HR 1.952 and 0.697 for patients with and without chemotherapy, respectively). The chemotherapy-MGMT interaction for OS was significant in both the surgery set (p = 0.045) and TCGA set (p = 0.034)., Conclusions: We demonstrated that high MGMT expression is an independent poor prognostic factor in MIBC patients with platinum-based adjuvant chemotherapy, but not in patients without chemotherapy. MGMT expression may be a potential predictor for administration of adjuvant chemotherapy.

Background: This study aimed to investigate the prognostic significance of NUCB2 in clear cell renal cell carcinoma., Patients and Methods: The study retrospectively enrolled a training set (182 patients) and a validation set (434 patients) with non-metastasis (pT1-3N0M0) ccRCC from two institutional medical centers of China. NUCB2 protein expression was evaluated by immunohistochemical staining of NUCB2 antibody, and its association with clinicopathological characteristics and clinical outcomes were evaluated. The NUCB2 mRNA transcription level was evaluated through TCGA KIRC cohort (190 patients). Prognostic accuracies were evaluated by C index and Akaike information criterion., Results: In ccRCC tissues, NUCB2 protein expression level was positively correlated with Fuhrman grade (P = 0.002 and P < 0.001, respectively). Patients with high NUCB2 mRNA transcription level (P = 0.005) and protein expression level (P = 0.024 and P < 0.001, respectively) had shorter cancer-specific survival in Kaplan-Meier survival curve. Moreover, multivariate analysis identified NUCB2 expression level as an independent prognostic factor for cancer-specific survival. Subgroup analysis suggested that NUCB2 expression significantly stratified pT1 stage patients (P < 0.001) rather than higher pT stage patients. Therefore, a new NNF prognosis model was developed to predict the cancer-specific survival in patients with pT1N0M0 stage (C-index = 0.743)., Conclusion: NUCB2 expression level is a powerful independent prognostic factor for CSS in patients with non-metastasis (pT1-3N0M0) ccRCC.

On the basis of aberrant interleukin-8 (IL-8) expression, a crucial angiogenesis factor and potential therapeutic target, in clear-cell renal cell carcinoma (ccRCC), this study aims to assess the prognostic significance of IL-8 in ccRCC. This retrospective study enrolled 271 patients who underwent nephrectomy for ccRCC in a single institution. The associations of IL-8 expression with clinical and pathological features were assessed using chi-squared tests. The impact on cancer-specific survival (CSS) and relapse-free survival (RFS) was analyzed using univariable and multivariable Cox regression models. The area under the receiver operating characteristic (ROC) curve (AUC) was used as an index of prognostic performance. Intratumoral IL-8 was found to be significantly elevated in ccRCC tissues compared with peritumor tissue and be predominately localized in the cytoplasm. Moreover, high IL-8 expression was positively correlated with Fuhrman grade (P < 0.001). Multivariate Cox regression analysis identified IL-8 as an independent adverse prognostic factor of CSS (P < 0.001) and RFS (P < 0.001), which could be incorporated into the traditional TNM staging system to improve the prognostic value for CSS and RFS in ccRCC patients. The predictive accuracy of traditional TNM stage model was significantly improved when IL-8 expression was added. Increased expression of IL-8 is a potential independent adverse prognostic biomarker for CSS and RFS in patients with ccRCC after nephrectomy.