BACKGROUND: Owing to the heterogeneity of prostate cancer (PCa), the clinical indicators traditionally fall short of meeting the requirements for personalized medicine. The realm of RNA modification has emerged as an increasingly relevant domain, shedding light on its pivotal role in tumor heterogeneity. However, the specific contributions of RNA modification regulators within the context of PCa remain largely unexplored.
METHODS: In this study, we undertook a literature review to summarize the common 8 types of RNA modifications (ac4c, AI, APA, m1A, m5c, m6A, m7G, Ψ) encompassing a total of 84 regulators. Moreover, we integrated multi-center cohorts with Ridge regression to develop the Regulators\' Co-Expression Score (RMRCoeS). Then we assessed the role of RMRCoeS in several clinical aspects such as biochemical recurrence (BCR), responses to chemotherapy, androgen receptor signaling inhibitor (ARSI) therapy and immunotherapy in PCa. Finally, we validated the cancer-promoting performance of five hub genes through immunohistochemistry and in vitro assays.
RESULTS: Within the mutation landscape of RNA modification regulators, we observed a relatively low overall mutation rate. Remarkably, RMRCoeS, comprising 81 RNA modification regulators, exhibited a notable capability for accurately predicting the prognosis and therapeutic responses in PCa patients subjected to BCR, chemotherapy, ARSI therapy, and immunotherapy. A high RMRCoeS was indicative of a poor prognosis and unfavorable therapy responses. Functional enrichment analysis unveiled that RMRCoeS may exert its influence on PCa progression through various metabolic pathways. Furthermore, a higher RMRCoeS showed a positive correlation with elevated CNV mutations. Lastly, we validated the oncogene effects of CPSF4, WBSCR22, RPUSD3, TRMT61A, and NSUN5-five hub regulators-within the context of PCa.
CONCLUSIONS: The function of different RNA modifications is interconnected. Comprising eight distinct RNA modifications\' regulators, RMRCoeS exhibits multifaceted roles in various aspects of PCa, including disease progression, prognosis, and responses to multiple therapies. Furthermore, we provide the initial validation of the oncogene effect associated with WBSCR22, RPUSD3, TRMT61A and NSUN5 in PCa. Our findings offer novel insights into the significance of RNA modifications in PCa personalized medicine.

OBJECTIVE: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa).
METHODS: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model\'s validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells.
RESULTS: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs\' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 μM showed increased proliferation and invasion capabilities.
CONCLUSIONS: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression.

OBJECTIVE: This study aimed to analyse the characteristics of biochemical recurrence after radical prostatectomy via bi-parametric magnetic resonance imaging.
METHODS: A total of 200 patients with radical prostatectomy admitted to our hospital from January 2016 to January 2021 were retrospectively enrolled as observation objects. According to whether there was biochemical recurrence after surgery, the patients were divided into the abnormal group (n = 62) and normal group (n = 138). Clinical data, encapsulation infiltration, seminal vesicle infiltration and prostate imaging report and data system (PI-RADS) were collected and compared between the two groups. Propensity score matching (PSM) was used to balance the baseline data of the two groups. Student\'s t-test and Chi-square test were used to analyse the data.
RESULTS: PSM was performed in a 1:1 ratio, and a total of 72 patients were included in the abnormal and normal groups. The baseline data of the patients in each group were not statistically significant. The incidence of extraperitoneal invasion and seminal vesicle invasion was higher in the abnormal group than in the normal group, and we observed a significant difference in PI-RADS scores between the two groups (p < 0.05). Extracapsular invasion, seminal vesicle invasion, PI-RADS score and biochemical recurrence were significantly correlated (p < 0.05). The PI-RADS score has a high value for predicting biochemical recurrence, with an area under the curve value of 0.824, sensitivity of 0.667, specificity of 0.861 and Youden index of 0.528.
CONCLUSIONS: Bi-parametric magnetic resonance imaging has a high predictive value in biochemical recurrence after radical prostatectomy, which can provide reference for early intervention measures.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been reported to be helpful to identify high-risk individuals of developing prostate cancer. Our aim is to investigate the relationship between NAFLD and biochemical recurrence in metastatic prostate cancer patients.
METHODS: We retrospectively investigated 602 patients with metastatic prostate cancer receiving the androgen deprivation therapy. Liver fat was estimated with liver-to-spleen ratio by computed tomography (CT) scans. The relationship between NAFLD and biochemical recurrence was investigated with Cox models. The model for biochemical recurrence was adjusted for multiple variables.
RESULTS: NAFLD was significantly associated with biochemical recurrence in patients with Gleason score ≥4+3 when adjusting for each of body mass index (hazards ratio [HR] = 1.38; 95% confidence interval [CI] = 1.08-1.77; p = 0.01), visceral adipose tissue (HR = 1.36; 95% CI = 1.07-1.74; p = 0.01), hypertension (HR = 1.41; 95% CI = 1.10-1.80; p = 0.01), and diabetes mellitus (HR = 1.42; 95% CI = 1.11-1.82; p = 0.01), using age and prostate-specific antigen level as potential confounder. The 2-year biochemical recurrence rate in the Gleason score ≥4+3 patients with and without NAFLD was 84.0% (100/119) and 72.2% (130/180), respectively (p = 0.018). The median biochemical recurrence free survival of the Gleason score ≥4+3 patients with and without NAFLD were 17 and 21 months, respectively (p = 0.005).
CONCLUSIONS: NAFLD is an independent risk factor for biochemical recurrence in patients with high-grade metastatic prostate cancer. If validated in prospective studies, future research should test whether treatment of NAFLD can lead to better prognosis.

UNASSIGNED: One of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its distant metastasis. However, the role of anoikis in PCa biochemical recurrence has not been fully elucidated.
UNASSIGNED: Differential expression analysis was used to identify anoikis-related genes based on the TCGA and GeneCards databases. Prognostic models were constructed utilizing LASSO regression, univariate and multivariate Cox regression analyses. Moreover, Gene Expression Omnibus datasets (GSE70770 and GSE46602) were applied as validation cohorts. Gene Ontology, KEGG and GSVA were utilized to explore biological pathways and molecular mechanisms. Further, immune profiles were assessed using CIBERSORT, ssGSEA, and TIDE, while anti-cancer drugs sensitivity was analyzed by GDSC database. In addition, gene expressions in the model were examined using online databases (Human Protein Atlas and Tumor Immune Single-Cell Hub).
UNASSIGNED: 113 differentially expressed anoikis-related genes were found. Four genes (EEF1A2, RET, FOSL1, PCA3) were selected for constructing a prognostic model. Using the findings from the Cox regression analysis, we grouped patients into groups of high and low risk. The high-risk group exhibited a poorer prognosis, with a maximum AUC of 0.897. Moreover, larger percentage of immune infiltration of memory B cells, CD8 Tcells, neutrophils, and M1 macrophages were observed in the high-risk group than those in the low-risk group, whereas the percentage of activated mast cells and dendritic cells in the high-risk group were lower. An increased TIDE score was founded in the high-risk group, suggesting reduced effectiveness of ICI therapy. Additionally, the IC50 results for chemotherapy drugs indicated that the low-risk group was more sensitive to most of the drugs. Finally, the genes EEF1A2, RET, and FOSL1 were expressed in PCa cases based on HPA website. The TISCH database suggested that these four ARGs might contribute to the tumor microenvironment of PCa.
UNASSIGNED: We created a risk model utilizing four ARGs that effectively predicts the risk of BCR in PCa patients. This study lays the groundwork for risk stratification and predicting survival outcomes in PCa patients with BCR.

UNASSIGNED: Aurora kinase A (AURKA) and tumor-infiltrating lymphocytes (TILs) are both known to play an essential role in tumorigenesis. However, the expression and prognostic value of the AURKA and TILs in medullary thyroid carcinoma (MTC) have not yet been investigated.
UNASSIGNED: Surgical specimens and clinical data of 137 patients diagnosed with MTC were collected. AURKA expression and TILs infiltration were quantified by immunohistochemistry and hematoxylin-eosin staining. Subsequently, the prognostic value of AURKA expression and TIL infiltration in MTC was evaluated.
UNASSIGNED: AURKA was highly expressed in patients with multifocal tumor, cervical lymph node metastasis, and an advanced TNM stage, indicating a high probability of recurrence. AURKA further exhibited a positive correlation with TILs (R = 0.44, P < 0.001). High expression of AURKA combined with a low numbers of TILs (AURKAhigh/TILslow) was identified as an independent prognostic factor for biochemical recurrence (odds ratio: 4.57, 95% confidence interval: 1.54-14.66, P < 0.01) and recurrence-free survival (hazard ratio: 3.64, 95% confidence interval: 1.52-8.71, P < 0.001). The combination of AURKA and TILs apparently improves the prognostic value for biochemical recurrence (area under the curve: 0.751) and structural recurrence (area under the curve: 0.836) of MTC. Notably, AURKAhigh/TILslow demonstrated a high value for prediction of distant or unresectable locoregional recurrence, with an overall accuracy of 86.9%.
UNASSIGNED: AURKAhigh is associated with the MTC malignancy. The combination of AURKAhigh/TILslow was identified as novel independent prognostic marker in MTC, predicting incurable disease recurrence with high accuracy.

BACKGROUND: Considering the age relevance of prostate cancer (PCa) and the involvement of the cGAS-STING pathway in aging and cancer, we aim to classify PCa into distinct molecular subtypes and identify key genes from the novel perspective of the cGAS-STING pathway. It is of significance to guide personalized intervention of cancer-targeting therapy based on genetic evidence.
METHODS: The 430 patients with PCa from the TCGA database were included. We integrated 29 key genes involved in cGAS-STING pathway and analyzed differentially expressed genes and biochemical recurrence (BCR)-free survival-related genes. The assessments of tumor stemness and heterogeneity and tumor microenvironment (TME) were conducted to reveal potential mechanisms.
RESULTS: PCa patients were classified into two distinct subtypes using AURKB, TREX1, and STAT6, and subtype 1 had a worse prognosis than subtype 2 (HR: 21.19, p < 0.001). The findings were validated in the MSKCC2010 cohort. Among subtype 1 and subtype 2, the top ten mutation genes were MUC5B, DNAH9, SLC5A10, ZNF462, USP31, SIPA1L3, PLEC, HRAS, MYOM1, and ITGB6. Gene set variation analysis revealed a high enrichment of the E2F target in subtype 1, and gene set enrichment analysis showed significant enrichment of base excision repair, cell cycle, and DNA replication in subtype 1. TME evaluation indicated that subtype 1 had a significantly higher level of T cells follicular helper and a lower level of plasma cells than subtype 2.
CONCLUSIONS: The molecular subtypes mediated by the cGAS-STING pathway and the genetic risk score may aid in identifying potentially high-risk PCa patients who may benefit from pharmacologic therapies targeting the cGAS-STING pathway.

BACKGROUND: The 17-gene Genomic Prostate Score (GPS) test has been clinically employed to predict adverse prognosis in prostate cancer. In this meta-analysis, we aimed to evaluate the prognostic value of the 17-gene GPS in patients with prostate cancer.
METHODS: Potentially relevant studies were obtained by searching PubMed, Web of Science, Embase databases from their inception to December 1, 2023. Studies were considered eligible if they evaluated the association of the 17-gene GPS with distant metastases, biochemical recurrence, or prostate cancer-specific mortality (PCSM) in prostate cancer patients. To estimate the prognostic value, we pooled the adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the high versus low GPS group or per 20-unit increase in GPS.
RESULTS: Seven cohort studies that reported on 8 articles comprising 1,962 patients satisfied the eligibility criteria. Meta-analysis showed that per 20-unit increase in GPS was significantly associated with distant metastases (HR 2.99; 95% CI 1.97-4.53), biochemical recurrence (HR 2.18; 95% CI 1.64-2.89), and PCSM (HR 3.14; 95% CI 1.86-5.30). Moreover, patients with high GPS (> 40 points) had an increased risk of distant metastases (HR 5.22; 95% CI 3.72-7.31), biochemical recurrence (HR 4.41; 95% CI 2.29-8.49), and PCSM (HR 3.81; 95% CI 1.74-8.33) than those with low GPS (≤ 40 points).
CONCLUSIONS: A higher 17-gene GPS significantly predicts distant metastases, biochemical recurrence, and PCSM in men with clinically localized prostate cancer. However, large-scale multicenter prospective studies are necessary to further validate these findings.

Ovarian cancer is a prevalent malignant tumor of the female reproductive system, often remaining concealed until it reaches an advanced stage. The standard treatment protocol includes cytoreductive surgery for ovarian cancer plus postoperative consolidation chemotherapy and maintenance therapy, although it carries a high recurrence rate. During the treatment period, chemotherapy can lead to bone marrow suppression, a condition known as Chemotherapy-Induced Myelosuppression (CIM). This suppression may necessitate dose reduction or chemotherapy treatment cycle delay. In severe cases, CIM can result in infection, fever, and potential harm to the patient\'s life. Here, we report a case of a female patient with ovarian malignant tumor of biochemical recurrence who treated with chemotherapy combined with Trilaciclib, following previous perioperative chemotherapy with occurrence of severe CIM. It involves an intravenous injection of Trilaciclib before chemotherapy, which significantly abates the side effects of chemotherapy, reduces the occurrence of severe CIM, improves the patients\' quality of life, and decreases the economic burden of hospitalization. We hope that this retrospective analysis of the case may serve as a reference in preventing and treating severe CIM during chemotherapy in some patients with malignant tumors, ultimately benefiting more patients with tumors.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a malignant tumor with low incidence. Currently, most studies have focused on the prognostic risk factors of MTC, whatever, time kinetic and risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) are yet to be elucidated.
METHODS: A retrospective study was conducted for 190 MTC patients. Risk factors related to calcitonin normalization (CN) and biochemical persistence/recurrence (BP) were analyzed. The predictors of calcitonin normalization time (CNT) and biochemical persistent/recurrent time (BPT) were identified. Further, the prognostic roles of CNT and BPT were also demonstrated.
RESULTS: The 5- and 10-year DFS were 86.7% and 70.2%, respectively. The 5- and 10-year OS were 97.6% and 78.8%, respectively. CN was achieved in 120 (63.2%) patients, whereas BP was presented in 76 (40.0%) patients at the last follow up. After curative surgery, 39 (32.5%) and 106 (88.3%) patients achieved CN within 1 week and 1 month. All patients who failed to achieve CN turned to BP over time and 32/70 of them developed structural recurrence. The median time of CNT and BPT was 1 month (1 day to 84 months) and 6 month (3 day to 63months), respectively. LNR > 0.23 and male gender were independent predictors for CN and BP. LNR > 0.23 (Hazard ratio (HR), 0.24; 95% CI,0.13-0.46; P < 0.01) and male gender (HR, 0.65; 95% CI, 0.42-0.99; P = 0.045) were independent predictors for longer CNT. LNR > 0.23 (HR,5.10; 95% CI,2.15-12.11; P < 0.01) was still the strongest independent predictor followed by preoperative serum Ctn > 1400ng/L (HR,2.34; 95% CI,1.29-4.25; P = 0.005) for shorter BPT. In survival analysis, primary tumor size > 2 cm (HR, 5.81; 95% CI,2.20-15.38; P < 0.01), CNT > 1 month (HR, 5.69; 95% CI, 1.17-27.61; P = 0.031) and multifocality (HR, 3.10; 95% CI, 1.45-6.65; P = 0.004) were independent predictor of DFS.
CONCLUSIONS: Early changes of Ctn after curative surgery can predict the long-term risks of biochemical and structural recurrence, which provide a useful real-time prognostic information. LNR significantly affect the time kinetic of biochemical prognosis. Tumor burden and CNT play a crucial role in MTC survival, the intensity of follow-up must be tailored accordingly.