Jie Dong’s research while affiliated with Nanjing University and other places

Background: Evidence from observational studies suggests an association between mental disorders and cancers. However, the causality of this association remains unclear. Methods: We collected genome-wide association study (GWAS) summary statistics of five mental disorders from the Psychiatric Genomics Consortium (PGC, 72,517 to 500,199 participants), paired with GWAS summary statistics of the risks of 18 cancer types from the UK Biobank (167,020 to 361,194 participants) and FinnGen database (110,521 to 264,701 participants). We conducted univariable and multivariable Mendelian randomization (MR) analyses to explore the causal relationships. Results: We identified ten causal associations between mental disorders and cancer risks. Notably, anorexia nervosa (AN) exhibits a causal association with a decreased risk of prostate cancer (β = -0.30, p = 1.61 × 10-6) and an elevated risk for stomach cancer (β = 0.47, p = 5.3 × 10-3). Bipolar disorder (BD) is causally linked to a reduced risk of pancreatic cancer (β = -5.13 × 10-4, p = 3.2 × 10-3). Major depression disorder (MDD) is causally associated with an elevated risk of bladder cancer (β = 1.84 × 10-3, p = 5.0 × 10-4) and kidney cancer (β = 1.40 × 10-3, p = 4.9 × 10-3). Additionally, we found the causal effect of skin melanoma on BD (β = -10.39, p = 2.1 × 10-4) and Schizophrenia (SCZ, β = -7.42, p = 3.3 × 10-4) with a bi-directional MR analysis. Moreover, we identified leukocyte count as a causal mediator of a causal association between AN and stomach cancer with a two-step MR analysis. Conclusions: In summary, our MR analysis reveals that mental disorders were causally associated with cancer risks.

Background The CD105+ cell clones isolated from renal cell carcinoma (RCC)were characterized as cancer stem cells. This study aimed to explore the antitumor mechanism of the transform growth factor-β(TGF-β) insensitive CD8+ T cells against CD105+ cells in vitro and vivo. Methods The CD105+ cell clones were isolated from primary RCC cell lines and characterized by the immunofluorescence, qRT-PCR and western-blotting analysis. The expression levels of TGF-β1 were examined in 105 RCC tissues and correlation regression analysis were performed. The tumor specific TGF-beta insensitive CD8+ T cells were expanded ex vivo as previously described. The naïve CD8+ T cells and PBS as control. The humanized SCID mice were challenged with injection of CD105+ cells before adoptive transfer. The antitumor appraisal including survival analysis, tumor burden and bioluminescent imaging examination. The presence of pulmonary metastases was evaluated pathologically and epithelial-mesenchymal transition related molecular were analyzed. Results The CD105+ cells were characterized with renal cancer stem cell for the high expression of Nanog, Oct4, Vimentin, Pax2 and high tumorigenicity. The TGF-beta-insensitive CD8+T cells showed the specific antitumor effect against CD105+ in vitro, were associated with suppressed pulmonary metastasis, and prolonged survival times, inhibited the epithelial-mesenchymal transition in tumor microenvironment. Conclusion Our results demonstrate that the TGF-beta insensitive CD8+T cells show the tumor-specific antitumor effect including reduce tumor burden, inhibit pulmonary metastasis by blockade the EMT mechanism existed in CD105+CSCs. This study may provide a new perspective and method for the immunotherapy in RCC.

Introduction Metastatic renal cell carcinoma (mRCC) with sarcomatoid features has a poor prognosis. Cytoreductive radical nephrectomy (CRN) can improve prognosis, but patient selection is unclear. This study aimed to develop a prediction model for selecting patients suitable for CRN. Materials and methods Patients with a diagnosis of mRCC with sarcomatoid features in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively reviewed. CRN benefit was defined as a survival time longer than the median overall survival (OS) in patients who did not receive CRN. A prediction nomogram was established and validated using the SEER cohort (training and internal validation) and an external validation cohort. Results Of 900 patients with sarcomatoid mRCC, 608 (67.6%) underwent CRN. OS was longer in the CRN group than in the non-CRN group (8 vs. 6 months, hazard ratio (HR) = 0.767, p = 0.0085). In the matched CRN group, 124 (57.7%) patients survived >6 months after the surgery and were considered to benefit from CRN. Age, T-stage, systematic therapy, metastatic site, and lymph nodes were identified as independent factors influencing OS after CRN, which were included in the prediction nomogram. The monogram performed well on the training set (area under the receiver operating characteristic (AUC) curve = 0.766, 95% confidence interval (CI): 0.687–0.845), internal validation set (AUC = 0.796, 95% CI: 0.684–0.908), and external validation set (AUC = 0.911, 95% CI: 0.831–0.991). Conclusions A nomogram was constructed and validated with good accuracy for selecting patients with sarcomatoid mRCC suitable for CRN.

Purpose This study presents a novel approach to predict postoperative biochemical recurrence (BCR) in prostate cancer (PCa) patients which involves constructing a signature based on anoikis-related genes (ARGs). Methods In this study, we utilised data from TCGA-PARD and GEO databases to identify specific ARGs in prostate cancer. We established a signature of these ARGs using Cox regression analysis and evaluated their clinical predictive efficacy and immune-related status through various methods such as Kaplan-Meier survival analysis, subject work characteristics analysis, and CIBERSORT method. Our findings suggest that these ARGs may have potential as biomarkers for prostate cancer prognosis and treatment. To investigate the biological pathways of genes associated with anoikis, we utilised GSVA, GO, and KEGG. The expression of ARGs was confirmed by the HPA database. Furthermore, we conducted PPI analysis to identify the core network of ARGs in PCa. Results Based on analysis of the TCGA database, a set of eight ARGs were identified as prognostic signature genes for prostate cancer. The reliability and validity of this signature were well verified in both the TCGA and GEO codifications. Using this signature, patients were classified into two groups based on their risk for developing BCR. There was a significant difference in BCR-free time between the high and low risk groups (P < 0.05).This signature serves as a dependable and unbiased prognostic factor for predicting biochemical recurrence (BCR) in prostate cancer (PCa) patients. It outperforms clinicopathological characteristics in terms of accuracy and reliability. PLK1 may play a potential regulatory role as a core gene in the development of prostate cancer. Conclusion This signature suggests the potential role of ARGs in the development and progression of PCa and can effectively predict the risk of BCR in PCa patients after surgery. It also provides a basis for further research into the mechanism of ARGs in PCa and for the clinical management of patients with PCa.

Objective: To explore the clinical, imaging, pathologic features, treatment, and prognostic outcomes in 23 cases of collecting duct carcinoma (CDC) from a single center. Methods: The clinical and imaging findings, pathological features, treatment methods, and outcomes of the 23 patients with CDC confirmed by microscopic examination between 2003 and 2020 at our institution were retrospectively reviewed. Descriptive statistics of demographic and clinical variables were applied. Kaplan-Meier method was used to analyze survival data and log-rank test statistic survival differences between groups. Cox regression analysis was employed to identify variables independently related to overall survival (OS). Results: A total of 23 patients with CDC were identified. The mean age was 50.8 years. Stage III or IV tumors were diagnosed in 82.6% of the patients at diagnosis. The average size of the tumor was 6.58 cm, and the left kidney was more involved than the right. The median OS was 12 months. The OS rates at 1 and 2 years were 43.5% and 26.1%, respectively. Twenty patients underwent nephrectomy, 3 underwent nephroureterectomy, and 9 (39.1%) patients received subsequent therapeutic interventions following surgery. Distant metastasis and no symptoms at initial diagnosis proved to be an independent factor of unfavorable survival in Cox regression analysis. Conclusions: CDC is a rare and highly aggressive malignant renal tumor, and most patients present at an advanced stage at initial diagnosis. More than half of the patients died within 1 year after surgery. Distant metastasis and no clinical symptoms at initial diagnosis were independent risk prognostic factors for patients with CDC.