Dong Zhang's research while affiliated with First Affiliated Hospital of China Medical University and other places

Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent malignant tumors of the urinary system, with a high recurrence and metastasis rate. Telomeres and long non-coding RNAs (lncRNAs) have been documented playing critical roles in cancer progression. However, the prognostic significance of telomere-related lncRNA (TRLs) in KIRC is less well-defined. The Cancer Genome Atlas database was applied to retrieve the expression profiles and corresponding clinical information of KIRC patients. To create the TRLs prognostic signature, univariate Cox regression, least absolute shrinkage and selection operator analyses were performed. The prognostic signature, comprised of nine prognostic TRLs, was developed and demonstrated superior prognostic ability for KIRC patients. Additionally, the risk score acted as an independent prognostic indicator. A nomogram incorporating age, grade, stage, and signature-based risk scores was also developed and exhibited excellent predictive accuracy. Several immune activities were associated with the signature, as determined by gene function analysis. Further analysis revealed differences in the status of immunity and the tumor microenvironment between low- and high-risk groups. Notably, KIRC patients with high-risk scores were more responsive to immunotherapy and chemotherapy. To summarize, our study developed a new prognostic signature consisting of nine telomere-related lncRNA that can precisely predict the prognosis of KIRC patients. The signature was shown to be of substantial value for the tumor microenvironment and tumor mutation burden, thereby contributing to a framework for the individualized treatment of patients.

Background The association between clear cell renal cell carcinoma (ccRCC) and disulfidoptosis remains to be thoroughly investigated. Methods We conducted multiple bioinformatics analyses, including prognostic analysis and cluster analysis, using R software. Additionally, we utilized Quantitative Real-time PCR to measure RNA levels of specific genes. The proliferation of ccRCC was assessed through CCK8 and colony formation assays, while the invasion and migration of ccRCC cells were evaluated using the transwell assay. Results In this study, utilizing data from multiple ccRCC cohorts, we identified molecules that contribute to disulfidoptosis. We conducted a comprehensive investigation into the prognostic and immunological roles of these molecules. Among the disulfidoptosis-related metabolism genes (DMGs), LRPPRC, OXSM, GYS1, and SLC7A11 exhibited significant correlations with ccRCC patient prognosis. Based on our signature, patients in different groups displayed varying levels of immune infiltration and different mutation profiles. Furthermore, we classified patients into two clusters and identified multiple functional pathways that play important roles in the occurrence and development of ccRCC. Given its critical role in disulfidoptosis, we conducted further analysis on SLC7A11. Our results demonstrated that ccRCC cells with high expression of SLC7A11 exhibited a malignant phenotype. Conclusions These findings enhanced our understanding of the underlying function of DMGs in ccRCC.

Objective: The novel coronavirus (severe acute respiratory syndrome coronavirus 2) has been spreading worldwide since December 2019, posing a serious danger to human health and socioeconomic development. A large number of clinical trials have revealed that coronavirus disease 2019 (COVID-19) results in multi-organ damage including the urogenital system. This study aimed to explore the potential mechanisms of genitourinary damage associated with COVID-19 infection through bioinformatics and molecular simulation analysis. Methods: We used multiple publicly available databases to explore the expression patterns of ACE2, TMPRSS2, and CD147 (Basigin [BSG]) in major organs in the healthy and disease-specific populations, particularly the genitourinary organs. Single-cell RNA sequencing was used to analyze the cell-specific expression patterns of ACE2, TMPRSS2, CD147, cytokine receptors, and cytokine interacting proteins in genitourinary organs, such as the bladder, kidney, prostate, and testis. Additionally, gene set enrichment analysis was used to investigate the relationship between testosterone levels and COVID-19 vulnerability in patients with prostate cancer. Results: The results revealed that ACE2, TMPRSS2, and CD147 were highly expressed in normal urogenital organs. Then, they were also highly expressed in multiple tumors and chronic kidney diseases. Additionally, ACE2, TMPRSS2, and CD147 were significantly expressed in a range of cells in urogenital organs according to single-cell RNA sequencing. Cytokine receptors and cytokine interacting proteins, especially CCL2, JUN, and TIMP1, were commonly highly expressed in urogenital organs. Finally, gene set enrichment analysis results showed that high testosterone levels in prostate cancer patients were significantly related to the JAK/STAT signaling pathway and the Toll-like receptor signaling pathway which were associated with COVID-19. Conclusion: Our study provides new insights into the potential mechanisms of severe acute respiratory syndrome coronavirus 2 damage to urogenital organs from multiple perspectives, which may draw the attention of urologists to COVID-19 and contribute to the development of targeted drugs.

Objective Evidence shows that gene mutation is a significant proportion of genetic factors associated with prostate cancer. The DNA damage response (DDR) is a signal cascade network that aims to maintain genomic integrity in cells. This comprehensive study was performed to determine the link between different DNA damage response gene mutations and prostate cancer. Materials and methods A systematic literature search was performed using PubMed, Web of Science, and Embase. Papers published up to February 1, 2022 were retrieved. The DDR gene mutations associated with prostate cancer were identified by referring to relevant research and review articles. Data of prostate cancer patients from multiple PCa cohorts were obtained from cBioPortal. The OR or HR and 95% CIs were calculated using both fixed-effects models (FEMs) and random-effects models (REMs). Results Seventy-four studies were included in this research, and the frequency of 13 DDR genes was examined. Through the analysis of 33 articles that focused on the risk estimates of DDR genes between normal people and PCa patients, DDR genes were found to be more common in prostate cancer patients (OR = 3.6293 95% CI [2.4992; 5.2705]). Also, patients in the mutated group had a worse OS and DFS outcome than those in the unmutated group ( P < .05). Of the 13 DDR genes, the frequency of 9 DDR genes in prostate cancer was less than 1%, and despite differences in race, BRCA2 was the potential gene with the highest frequency (REM Frequency = .0400, 95% CI .0324 - .0541). The findings suggest that mutations in genes such as ATR, BLM, and MLH1 in PCa patients may increase the sensitivity of Olaparib, a PARP inhibitor. Conclusion These results demonstrate that mutation in any DDR pathway results in a poor prognosis for PCa patients. Furthermore, mutations in ATR, BLM, and MLH1 or the expression of POLR2L, PMS1, FANCE, and other genes significantly influence Olaparib sensitivity, which may be underlying therapeutic targets in the future.

Extensive research indicates that tumor stemness promotes tumor progression. Nonetheless, the underlying roles of stemness-related genes in renal clear cell carcinoma (ccRCC) are unclear. Data used in bioinformatics analysis were downloaded from The Cancer Genome Atlas (TCGA) database. Moreover, the R software, SPSS, and GraphPad Prism 8 were used for mapping and statistical analysis. First, the stemness index of each patient was quantified using a machine learning algorithm. Subsequently, the differentially expressed genes between high and low stemness index were identified as stemness-related genes. Based on these genes, a stable and effective prognostic model was identified to predict the overall survival of patients using a random forest algorithm (Training cohort; 1-year AUC: 0.67; 3-year AUC: 0.79; 5-year AUC: 0.73; Validation cohort; 1-year AUC: 0.66; 3-year AUC: 0.71; 5-year AUC: 0.7). The model genes comprised AC010973.2 , RNU6-125P , AP001209.2 , Z98885.1 , KDM5C-IT1, and AL021368.3 . Due to its highest importance evaluated by randomforst analysis, the AC010973.2 gene was selected for further research. In vitro experiments demonstrated that AC010973.2 is highly expressed in ccRCC tissue and cell lines. Meanwhile, its knockdown could significantly inhibit the proliferation of ccRCC cells based on colony formation and CCK8 assays. In summary, our findings reveal that the stemness-related gene AC01097.3 is closely associated with the survival of patients. Besides, it remarkably promotes cell proliferation in ccRCC, hence a novel potential therapeutic target.

This study aims to explore the factors influencing the success rate of the microdissection testicular sperm extraction (Micro-TESE) in patients with nonobstructive azoospermia (NOA) and cryptorchidism. Clinical data of 162 patients with cryptorchidism who underwent Micro-TESE due to infertility from December 2015 to May 2020 in the First Affiliated Hospital of Nanjing Medical University were analyzed retrospectively. In the univariate analysis, significant differences in the age of patient at the time of orchidopexy (median [interquartile range, IQR]: 7.0 [4.0-11.0] years vs 11.5 [9.0-14.5] years, P < 0.001), interval between orchidopexy and Micro-TESE (mean ± standard deviation: 17.5 ± 5.0 years vs 14.4 ± 4.4 years, P < 0.001), severity of cryptorchidism (unilateral [62.8%] vs bilateral [31.6%], P < 0.001; location of cryptorchidism, intra-abdominal [27.3%] vs inguinal [44.8%] vs suprascrotal [66.7%], P < 0.001), volume of the dominant testis (median [IQR]: 17.00 [15.00-19.00] ml vs 14.50 [11.75-16.25] ml, P < 0.001), and levels of follicle-stimulating hormone (FSH; P = 0.004) and testosterone (P = 0.006) were observed between the successful and failed sperm extraction groups. After conducting the multivariate analysis, four of these factors, including unilateral/bilateral cryptorchidism (P < 0.001), location of cryptorchidism (P = 0.032), age of orchidopexy (P < 0.001), and dominant testicular volume, were adopted in the clinical prediction model to evaluate preoperatively the success rate of Micro-TESE for patients with NOA and cryptorchidism. The likelihood of successful sperm retrieval by Micro-TESE in men with NOA and cryptorchidism increased in patients with mild forms of cryptorchidism.

Immune microenvironment of prostate cancer (PCa) is implicated in disease progression. However, previous studies have not fully explored PCa immune microenvironment. This study used ssGSEA algorithm to explore expression levels of 53 immune terms in a combined PCa cohort (eight cohorts; 1,597 samples). The top 10 immune terms were selected based on the random forest analysis and used for immune-related risk score (IRS) calculation. Furthermore, we explored differences in clinical and genomic features between high and low IRS groups. An IRS signature based on the 10 immune terms showed high prediction potential for PCa prognosis. Patients in the high IRS group showed significantly higher percentage of immunotherapy response factors, implying that IRS is effective in predicting immunotherapy response rate. Furthermore, consensus clustering was performed to separate the population into three IRSclusters with different clinical outcomes. Patients in IRScluster3 showed the worst prognosis and highest immunotherapy response rate. On the other hand, patients in IRScluster2 showed better prognosis and low immunotherapy response rate. In addition, VGLL3, ANPEP, CD38, CCK, DPYS, CST2, COMP, CRISP3, NKAIN1, and F5 genes were differentially expressed in the three IRSclusters. Furthermore, CMap analysis showed that five compounds targeted IRS signature, thioridazine, trifluoperazine, 0175029-0000, trichostatin A, and fluphenazine. In summary, immune characteristics of PCa tumor microenvironment was explored and an IRS signature was constructed based on 10 immune terms. Analysis showed that this signature is a useful tool for prognosis and prediction of immunotherapy response rate of PCa.

Drinking water is an important natural resource. For many people around the world, especially in developing countries, access to safe drinking water is still a distant dream. An increasing number of human activities and industrialization have caused various physical, chemical and biological pollutants to enter water bodies, affecting human health. Efforts to figure out an effective method to predict water pollution poisons and human diseases have increased worldwide. Water pollutants contain a vast number of additives such as perfluorinated chemicals, polybrominated diphenyl ethers, phthalate, nanomaterials, insecticides, microcystins, heavy metal and pharmacologies. Here, we explored an integrative approach to identify genes, biological processes, molecular functions, and diseases linked to exposure to these water pollutants. These processes and functions affected by water pollutants are related to the many diseases, including colonic neoplasms, breast neoplasms hepatitis B, bladder cancer and human cytomegalovirus infection. Therefore, conducting an integrative toxicogenomic analysis of water pollutants are more appropriate for evaluating the potential effects of plastics in human health.