Kidney cancer ranks as one of the top 10 causes of cancer death; this cancer is difficult to detect, difficult to treat, and poorly understood. The most common subtype of kidney cancer is clear cell renal cell carcinoma (ccRCC) and its progression is influenced by complex gene interactions. Few clinical studies have investigated the molecular markers associated with the progression of ccRCC. In this study, we collected microarray profiles of 72 ccRCCs and matched normal samples to identify differentially expressed genes (DEGs). Then a weighted gene co-expression network analysis (WGCNA) was conducted to identify co-expressed gene modules. By relating all co-expressed modules to clinical features, we found that the brown module and Fuhrman grade had the highest correlation (r = −0.8, p = 1e-09). Thus, the brown module was regarded as a clinically significant module and subsequently analyzed. Functional annotation showed that the brown module focused on metabolism-related biological processes and pathways, such as fatty acid oxidation and amino acid metabolism. We then performed a protein-protein interaction (PPI) network to identify the hub nodes in the brown module. It is worth noting that only one candidate, acetyl-CoA acetyltransferase (ACAT1), was considered to be the final target most relevant to the Fuhrman grade of ccRCC, by applying the intersection of hub genes in the co-expressed network and the PPI network. ACAT1 was subsequently validated using another two external microarray datasets and the TCGA dataset. Intriguingly, validation results indicated that ACAT1 was negatively correlated with four grades of ccRCC, which was also consistent with our results from qRT-PCR analysis and immunohistochemistry staining of clinical samples. Overexpression of ACAT1 inhibited the proliferation and migration of human ccRCC cells in vitro. In addition, the Kaplan-Meier survival curve showed that patients with a lower expression of ACAT1 showed a significantly lower overall survival rate and disease-free survival rate, indicating that ACAT1 could act as a prognostic and recurrence/progression biomarker of ccRCC. In summary, we found and confirmed that ACAT1 might help to identify the progression of ccRCC, which might have important clinical implications for enhancing risk stratification, therapeutic decision, and prognosis prediction in ccRCC patients.

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WAP four-disulfide core domain 2 (WFDC2) is a small secretory protein that has been widely studied in ovarian cancer. It has been proven that WFDC2 promotes proliferation and metastasis in ovarian cancer, and serves as a diagnostic biomarker. However, the specific function of WFDC2 in prostate cancer has not been reported. Here, we first screened the diagnostic marker and favorable prognostic factor WFDC2 in prostate cancer by bioinformatics. WFDC2 expression was negatively correlated with Gleason score and metastasis in prostate cancer. Then, we revealed that overexpression of WFDC2, and addition of recombinant protein HE4 can significantly inhibit prostate cancer metastasis in vivo and in vitro. By co-immunoprecipitation and co-localization assays, we proved that WFDC2 binds to the extracellular domain of epidermal growth factor receptor (EGFR). Immunoblot showed that WFDC2 overexpression and recombinant protein HE4 addition inactivated the EGFR/AKT/GSK3B/Snail signaling pathway, and then restrained the progression of epithelial-mesenchymal transition. In conclusion, our study identified that the tumor suppressor WFDC2 can suppress prostate cancer metastasis by inactivating EGFR signaling.

Based on accumulating evidence, transient receptor potential (TRP) ion channels may play important roles in the occurrence and the progression of cancer. TRP melastatin 8 (TRPM8), a member of the TRP family, functions as a Ca 2+-permeable channel and regulates various physiological and pathological processes. However, the effects of TRPM8 on bladder cancer (BCa) and its underlying mechanisms have not been elucidated. Methods: BCa tissues and matched noncancerous tissues were collected to examine the expression of the TRPM8 mRNA and protein using qRT-PCR, Western blotting and immunofluorescence staining. Meanwhile, the effect of knockdown or inhibition of the activity of the TRPM8 protein on the proliferation, migration and ROS metabolism of bladder cancer cells was detected using the MTT assay, clonogenic survival assay, Transwell chamber migration assay, and reactive oxygen species (ROS) detection, respectively. Furthermore, a mouse model transplanted with BCa cells was established to assess tumor growth after TRPM8 expression was inhibited in vivo. Results: Compared with the noncancerous tissues, the levels of TRPM8 in BCa tissues were significantly increased. Knockdown or inhibition of the activity of the TRPM8 protein in BCa cells reduced cell proliferation and migration. Moreover, the production of ROS was increased in cells treated with siTRPM8, which was accompanied by increased levels of Catalase, HO-1 and SOD2. Furthermore, a mouse model transplanted with the stable TRPM8-deficient T24 cell line was established, demonstrating that knockdown of TRPM8 delayed tumor growth in vivo. Discussion: TRPM8 might play an essential for BCa tumor progression and metastasis by interfering with BCa cell proliferation, motility, ROS metabolism and migration.

The aim of this study was to determine clinical recrudescent risk factors of 477 patients with newly discovered nonmuscle-invasive bladder cancer (NMIBC) (Ta-T1) in our hospital, and based on these factors, to establish a recurrence risk prediction model of each NMIBC patient. This study included 477 patients with newly discovered NMIBC (Ta-T1) from January 2012 to December 2016; all patients were treated surgically by transurethral resection of bladder tumor (TURBT). The outcomes of patients were with or without recurrence within 2 years. The nomograms were based on Cox regression analyses, and the calibration curves were founded to evaluate the agreements of the predicted probability with the actual observed probability. Of the 477 patients with NMIBC, 392 were males (82.2%) and 85 were females (17.8%), with median age 64 years. Recurrence was identified in 327 cases (68.6%). The results showed that old age, female sex, smoking history, large size of tumor, multifocal tumors, high grade, and high stage are risk factors for NMIBC recurrence, whereas no significant association was seen between tumor location and recurrence in our study. Based on the results of Cox regression analyses, several independent risk factors, including smoking history, tumor size, multifocal, immediate infusion therapy, T stage, and tumor grade, were used to establish a nomogram to calculate the recurrence probability of each NMIBC patient, and the calibration curve displayed that this nomogram had a great value of prediction. Old age, female sex, smoking history, large size of tumor, multifocal tumors, high grade, and high stage are risk factors for NMIBC recurrence, whereas immediate infusion therapy is a protective factor. And a nomogram was established as a prediction model to calculate the recurrence probability of NMIBC patients.