The complex interplay of tumor-infiltrating cells in driving therapeutic resistance pathways.

Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within the tumor microenvironment (TME) have deepened our understanding of the mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug resistance suggesting that targeting the TME could be a viable strategy to combat this issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, and angiogenesis, contribute to drug resistance could be a viable strategy to combat this issue. Overexpression of STAT3 is commonly associated with drug-resistant cancer cells or stromal cells. Current research often generalizes the impact of stromal cells on resistance, lacking specificity and statistical robustness. Thus, future research should take notice of this issue and aim to provide high-quality evidence. Despite the existing limitations, targeting the TME to overcome therapy resistance hold promising and valuable potential.

Relationship between clonal evolution and drug resistance in bladder cancer: A genomic research review.

Bladder cancer stands as a prevalent global malignancy, exhibiting notable sex-based variations in both incidence and prognosis. Despite substantial strides in therapeutic approaches, the formidable challenge of drug resistance persists. The genomic landscape of bladder cancer, characterized by intricate clonal heterogeneity, emerges as a pivotal determinant in fostering this resistance. Clonal evolution, encapsulating the dynamic transformations within subpopulations of tumor cells over time, is implicated in the emergence of drug-resistant traits. Within this review, we illuminate contemporary insights into the role of clonal evolution in bladder cancer, elucidating its influence as a driver in tumor initiation, disease progression, and the formidable obstacle of therapy resistance.

Unraveling links between aging, circadian rhythm and cancer: Insights from evidence-based analysis.

Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.

Cellular landscape of tumour microenvironment in prostate cancer.

Prostate cancer is still a public health priority in men and the impact of this disease will be more pronounced with the ageing of the world's population. Clinical heterogeneity of prostate cancer is reflected in spatial and clonal genomic diversity. Accumulating evidence demonstrates that the malignant behaviour of cancer is not only attributed to cancer cells but also fundamentally affected by stromal activity and controlled by various mechanisms of the tumour microenvironment. Data on prostate cancer in this study was derived from seven GEO datasets and the TCGA database. We analyzed the tumour microenvironment of prostate cancer in terms of clinical process, T stage and Gleason score using EPIC and xCell algorithms. We also analyzed the common immune checkpoints. In this study, we confirmed remarkable tumour tissue remodelling in the development of prostate cancer and further demonstrated the importance of cancer-related fibroblasts in the biochemical recurrence and metastasis for patients with prostate cancer undergoing radical radiotherapy or prostatectomy. In addition, we found that NRP1, CD200, TNFSF18 and CD80 might be the potential targets for prostate cancer.

Focal ablation therapy presents promising results for selectively localized prostate cancer patients.

Due to its lower risk of consequences when compared to a radical approach, focal treatment is a viable and minimally invasive option for treating specific localized prostate cancer. Although several recent good non-randomized trials have suggested that focused therapy may be an alternative choice for some patients, additional high-quality evidence is needed before it can be made widely available as a conventional treatment. As a result, we have summarized the most recent findings from the 38th Annual European Association of Urology Congress, one of the most renowned annual conferences in the area of urology, regarding focal ablation therapy for patients with localized prostate cancer. Additionally, we also provided clinical trials in progress for researchers to better understand the current research status of this field.

Unveiling clinical significance and tumor immune landscape of CXCL12 in bladder cancer: Insights from multiple omics analysis.

Objective: The interplay between chemokine C-X-C motif ligand 12 (CXCL12) and its specific receptors is known to trigger various signaling pathways, contributing to tumor proliferation and metastasis. Consequently, targeting this signaling axis has emerged as a potential strategy in cancer therapy. However, the precise role of CXCL12 in clinical therapy, especially in immunotherapy for bladder cancer (BCa), remains poorly elucidated. Methods: We gathered multiple omics data from public databases to unveil the clinical relevance and tumor immune landscape associated with CXCL12 in BCa patients. Univariate and multivariate Cox regression analyses were employed to assess the independent prognostic significance of CXCL12 expression and formulate a nomogram. The expression of CXCL12 in BCa cell lines and clinical tissue samples was validated using enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry (IHC). Results: While transcriptional expression of CXCL12 exhibited a decrease in nearly all tumor tissues, CXCL12 methylation expression was notably increased in BCa tissues. Single-cell RNA analysis highlighted tissue stem cells and endothelial cells as the primary sources expressing CXCL12. Abnormal CXCL12 expression, based on transcriptional and methylation levels, correlated with various clinical characteristics in BCa patients. Functional analysis indicated enrichment of CXCL12 and its co-expression genes in immune regulation and cell adhesion. The immune landscape analysis unveiled a significant association between CXCL12 expression and M2 macrophages (CD163+ cells) in BCa tissues. Notably, CXCL12 expression emerged as a potential predictor of immunotherapy response and chemotherapy drug sensitivity in BCa patients. Conclusions: Taken together, these findings suggest aberrant production of CXCL12 in BCa tissues, potentially influencing the treatment responses of affected individuals.

Developing an immune-related gene prognostic index associated with progression and providing new insights into the tumor immune microenvironment of prostate cancer.

We developed an immune-related gene prognostic index (IGPI) associated with progression and provided new insights into the tumour immune microenvironment (TIME) for prostate cancer (PCA) patients undergoing radical prostatectomy. All analyses were conducted with R software (version 3.6.3) and its suitable packages. Meta-analysis was performed with STATA 16.0. TUBB3, WDR62 and PPARGC1A were finally identified to establish the IGPI score. The IGPI score increased with the augment of the Gleason score and T stage, as well as biochemical recurrence (BCR) and prostate specific antigen (PSA). Patients with a higher IGPI score were at a higher risk of progress (HR: 2·88; 95%CI: 95%CI: 1·80-4·61). Gene set enrichment analysis indicated that patients in high-risk group were positively associated with mismatch repair, cell cycle, DNA replication, base excision repair, nucleotide excision repair, homologous recombination and pyrimidine metabolism. We observed that patients in the high-risk group had significantly higher tumour mutation burden score and microsatellite instability score than those in the low-risk group. For analysis of immune checkpoint, ADORA2A, CD80, TNFRSF4, TNFRSF18 and TNFRSF25 were differentially expressed between no progress and progress groups and were significantly associated with progress free survival. We observed positive correlations between the IGPI score and lymphoid immune cells, macrophages M2 and immune score, while negative association between the IGPI score and dendritic cells, fibroblasts, stromal score and microenvironment score. In conclusion, the IGPI score constructed in this study might serve as an independent risk factor associated with PCA progression. ADORA2A, CD80, TNFRSF4, TNFRSF18 and TNFRSF25 might be the potential targets in the treatment of PCA.

A gene prognostic index from cellular senescence predicting metastasis and radioresistance for prostate cancer.

BACKGROUND: Senescent cells have been identified in the aging prostate, and the senescence-associated secretory phenotype might be linked to prostate cancer (PCa). Thus, we established a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and radioresistance in PCa. METHODS: We used Lasso and Cox regression analysis to establish the CSGPI. Clinical correlation, external validation, functional enrichment analysis, drug and cell line analysis, and tumor immune environment analysis were conducted. All analyses were conducted with R version 3.6.3 and its suitable packages. RESULTS: We used ALCAM and ALDH2 to establish the CSGPI risk score. High-risk patients experienced a higher risk of metastasis than their counterparts (HR: 10.37, 95% CI 4.50-23.93, p < 0.001), consistent with the results in the TCGA database (HR: 1.60, 95% CI 1.03-2.47, p = 0.038). Furthermore, CSGPI had high diagnostic accuracy distinguishing radioresistance from no radioresistance (AUC: 0.938, 95% CI 0.834-1.000). GSEA showed that high-risk patients were highly associated with apoptosis, cell cycle, ribosome, base excision repair, aminoacyl-tRNA biosynthesis, and mismatch repair. For immune checkpoint analysis, we found that PDCD1LG2 and CD226 were expressed at significantly higher levels in patients with metastasis than in those without metastasis. In addition, higher expression of CD226 significantly increased the risk of metastasis (HR: 3.65, 95% CI 1.58-8.42, p = 0.006). We observed that AZD7762, PHA-793887, PI-103, and SNX-2112 might be sensitive to ALDH2 and ALCAM, and PC3 could be the potential cell line used to investigate the interaction among ALDH2, ALCAM, and the above drugs. CONCLUSIONS: We found that CSGPI might serve as an effective biomarker predicting metastasis probability and radioresistance for PCa and proposed that immune evasion was involved in the process of PCa metastasis.

Mitochondrial Aldehyde Dehydrogenase 2 Represents a Potential Biomarker of Biochemical Recurrence in Prostate Cancer Patients.

BACKGROUND: We aimed to explore the role of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in prostate cancer (PCa) patients and provide insights into the tumor immune microenvironment (TME) for those patients undergoing radical radiotherapy. METHODS: We performed all analyses using R version 3.6.3 and its suitable packages. Cytoscape 3.8.2 was used to establish network of competing endogenous RNAs (ceRNAs). RESULTS: Downregulation of ADLH2 was significantly associated with higher risk of BCR-free survival (HR: 0.40, 95%CI: 0.24-0.68, p = 0.001) and metastasis-free survival (HR: 0.21, 95%CI: 0.09-0.49, p = 0.002). Additionally, ALDH2 repression contributed to significantly shorter BCR-free survival in the TCGA database (HR: 0.55, 95%CI: 0.33-0.93, p = 0.027). For immune checkpoints, patients that expressed a higher level of CD96 had a higher risk of BCR than their counterparts (HR: 1.79, 95%CI: 1.06-3.03, p = 0.032), as well as NRP1 (HR: 2.18, 95%CI: 1.29-3.69, p = 0.005). In terms of the TME parameters, the spearman analysis showed that ALDH was positively associated with B cells (r: 0.13), CD8+ T cells (r: 0.19), neutrophils (r: 0.13), and macrophages (r: 0.17). Patients with higher score of neutrophils (HR: 1.75, 95%CI: 1.03-2.95, p = 0.038), immune score (HR: 1.92, 95%CI: 1.14-3.25, p = 0.017), stromal score (HR: 2.52, 95%CI: 1.49-4.26, p = 0.001), and estimate score (HR: 1.81, 95%CI: 1.07-3.06, p = 0.028) had higher risk of BCR than their counterparts. Our ceRNA network found that PART1 might regulate the expression of ALDH via has-miR-578 and has-miR-6833-3p. Besides, PHA-793887, PI-103, and piperlongumine had better correlations with ALDH2. CONCLUSIONS: We found that ALDH2 might serve as a potential biomarker predicting biochemical recurrence for PCa patients.

Assessment of the intrinsic radiosensitivity of glioma cells and monitoring of metabolite ratio changes after irradiation by 14.7-T high-resolution ¹H MRS.

Gliomas are the most common type of primary brain tumor. Radiation therapy (RT) is the primary adjuvant treatment to eliminate residual tumor tissue after surgery. However, the current RT guided by conventional imaging is unsatisfactory. A fundamental question is whether it is possible to further enhance the effectiveness and efficiency of RT based on individual radiosensitivity. In this research, to probe the correlation between radiosensitivity and the metabolite characteristics of glioma cells in vitro, a perchloric acid (PCA) extracting method was used to obtain water-soluble metabolites [such as N-acetylaspartate (NAA), choline (Cho), creatine (Cr) and succinate (Suc)]. Spectral patterns from these processed water-soluble metabolite samples were acquired by in vitro 14.7-T high-resolution ¹H MRS. Survival fraction analysis was performed to test the intrinsic radiosensitivity of glioma cell lines. Good ¹H MRS of PCA extracts from glioma cells was obtained. The radiosensitivity of glioma cells correlated positively with the Cho/Cr and Cho/NAA ratios, but negatively with the Suc/Cr ratio. Irradiation of the C6 cell line at different X-ray dosages led to changes in metabolite ratios and apoptotic rates. A plateau phase of metabolite ratio change and a decrease in apoptotic rate were found in the C6 cell line. We conclude that in vitro high-resolution ¹H MRS possesses the sensitivity required to detect subtle biochemical changes at the cellular level. ¹H MRS may aid in the assessment of the individual radiosensitivity of brain tumors, which is pivotal in the identification of the biological target volume.

Efficiency of transurethral en-bloc resection vs. conventional transurethral resection for non-muscle-invasive bladder cancer: An umbrella review.

BACKGROUND: En-Bloc transurethral resection of bladder tumor (ERBT) was clinically used to resect non-muscle-invasive bladder cancer (NMIBC). However, discrepancies persist regarding the comparisons between ERBT and conventional transurethral resection of bladder tumor (cTURBT). METHODS: We conducted a comprehensive search in PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and performed manual searches of reference lists to collect and extract data. Data evaluation was carried out using Review Manager 5.4.0, Rx64 4.1.3, and relevant packages. RESULTS: There were nine eligible meta-analyses and nine eligible RCTs in our study. NMIBC patients undergoing ERBT were significant associated with a lower rate of bladder perforation and obturator nerve reflex compared to those receiving cTURBT. Our pooled result indicated that ERBT and cTURBT required similar operation time. Regarding postoperative outcomes, ERBT demonstrated superior performance compared to cTURBT in terms of detrusor muscle presence, catheterization time, and residual tumor. ERBT exhibited a higher rate of three-month recurrence-free survival (RFS) compared to those receiving cTURBT (p < 0.05; I2 = 0%). In bipolar subgroup, ERBT had a significant better 12-month RFS than cTURBT (p < 0.05; I2 = 0%). Simultaneously, the exclusion of Hybrid Knife data revealed a significant improvement in 12-month RFS associated with ERBT (p < 0.05; I2 = 50%). CONCLUSION: Using a combination of umbrella review and meta-analysis, we demonstrated that ERBT had better or comparable perioperative outcome and improved 3 and 12 month RFS than cTURBT. We suggest that ERBT maybe a better surgical method for patients with NMIBC compared with cTURBT.

Efficiency of bladder-sparing strategies for bladder cancer: an umbrella review.

Bladder preservation (BP) has emerged as a clinical alternative to radical cystectomy (RC) for alleviating the substantial physical and psychological burden imposed on localized bladder cancer patients. Nevertheless, disparities persist in the comparative evaluations of BP and RC. We aimed to address the disparities between BP and RC. An umbrella review and meta-analysis were conducted to explore these disparities. We extracted data from meta-analyses and randomized controlled trials (RCTs) selected after searching PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Review Manager 5.4.0 and R x64 4.1.3 were used to evaluate the collected data. Our study included 11 meta-analyses and 3 RCTs. In terms of progression-free survival, all the meta-analyses reported that patients with localized bladder cancer who underwent BP exhibited outcomes comparable to those who underwent RC. Meta-analyses regarding the outcomes of cancer-specific survival (CSS) and overall survival (OS) are controversial. To solve these issues, we conducted a pooled analysis of CSS data, which supported the similarity of CSS between BP and RC with no significant heterogeneity [odds ratio (OR): 1.2; 95% confidence interval (CI): 0.71-2.02; I2 = 26%]. Similarly, the pooled OS results extracted from three RCTs indicated the comparability of OS between BP and RC with no significant heterogeneity (OR: 1.12; 95% CI: 0.41-3.07; I2 = 33%). A combination of umbrella review and meta-analysis results suggested that BP had survival rates comparable to those of RC. We suggest that BP may be a more eligible therapy than RC for patients with localized muscle-invasive bladder cancer. This conclusion warrants further validation through randomized controlled trials.

A Prognostic Index Derived From LASSO-Selected Preoperative Inflammation and Nutritional Markers for Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: There is an urgent need to identify a robust predictor for BCG response in patients with non-muscle-invasive bladder cancer (NMIBC). We aimed to employ the Lasso regression model for the selection and construction of an index (BCGI) utilizing inflammation and nutrition indicators to predict the response to BCG therapy. METHODS: After acquiring the ethics approval, we searched the electric medical records in our institution and performed data screening. Then, we developed the BCGI using a Lasso regression model and subsequently evaluated its performance in both the train and internal test datasets through Kaplan-Meier survival curves and Cox regression analysis. Then, we also evaluated the prognostic value of BCGI alongside the EAU2021 model. RESULTS: The training dataset and internal test dataset contained 295 and 196 patients, respectively. Referring to the Lasso results, BCGI consisted of hemoglobin, albumin, and platelet count, which could significantly predict the recurrence of NMIBC patients who accepted BCG in train (P = .012) and test (P = .004) datasets. The BCGI also exhibited statistically prognostic value in no smoking history, World Health Organization high grade, and T1 subgroups, both in train and test datasets. In multivariable analysis, BCGI exhibited independent prognostic value in train (P = .012) and test (P = .012) datasets. Finally, we constructed a nomogram that consisted of smoking history, T stage, World Health Organization grade, tumor size, and BCGI. Then, BCGI demonstrated significant independent prognostic value in NMIBC patients treated with BCG, a result not observed with the EAU2021 score or classification. CONCLUSION: Based on the results, we reasonably suggest that BCGI may be a useful predictor for NMIBC patients who accepted BCG. Furthermore, we have demonstrated the efficacy of constructing a prognostic index using clinical factors and a Lasso regression model, a versatile approach applicable to various medical conditions.

Natural products and derivatives in renal, urothelial and testicular cancers: Targeting signaling pathways and therapeutic potential.

BACKGROUND: Natural products have demonstrated significant potential in cancer drug discovery, particularly in renal cancer (RCa), urothelial carcinoma (UC), and testicular cancer (TC). PURPOSE: This review aims to examine the effects of natural products on RCa, UC and TC. STUDY DESIGN: systematic review METHODS: PubMed and Web of Science databases were retrieved to search studies about the effects of natural products and derivatives on these cancers. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: This review highlighted their diverse impacts on key aspects such as cell growth, apoptosis, metastasis, therapy response, and the immune microenvironment. Natural products not only hold promise for novel drug development but also enhance the efficacy of existing chemotherapy and immunotherapy. Importantly, we exert their effects through modulation of critical pathways and target genes, including the PI3K/AKT pathway, NF-κB pathway, STAT pathway and MAPK pathway, among others in RCa, UC, and TC. CONCLUSION: These mechanistic insights provide valuable guidance for researchers, facilitating the selection of promising natural products for cancer management and offering potential avenues for further gene regulation studies in the context of cancer treatment.

An endothelial-related prognostic index for bladder cancer patients.

BACKGROUND: Within the tumor microenvironment, endothelial cells hold substantial sway over bladder cancer (BC) prognosis. Herein, we aim to elucidate the impact of endothelial cells on BC patient outcomes by employing an integration of single-cell and bulk RNA sequencing data. METHODS: All data utilized in this study were procured from online databases. R version 3.6.3 and relevant packages were harnessed for the development and validation of an endothelial-associated prognostic index (EPI). RESULTS: EPI was formulated, incorporating six genes (CYTL1, FAM43A, GSN, HSPG2, RBP7, and SLC2A3). EPI demonstrated significant prognostic value in both The Cancer Genome Atlas (TCGA) and externally validated dataset. Functional results revealed a profound association between EPI and endothelial cell functionality, as well as immune-related processes. Our findings suggest that patients with low-risk EPI scores are more likely to respond positively to immunotherapy, as indicated by immune checkpoint activity, immune infiltration, tumor mutational burden, stemness index, TIDE, and IMvigor210 analyses. Conversely, individuals with high-risk EPI scores exhibited heightened sensitivity to cisplatin, docetaxel, and gemcitabine treatment regimens. CONCLUSION: We have effectively discerned pivotal genes from the endothelial cell perspective and constructed an EPI for BC patients, thereby offering promising prospects for precision medicine.

Biological clock regulation by the PER gene family: a new perspective on tumor development.

The Period (PER) gene family is one of the core components of the circadian clock, with substantial correlations between the PER genes and cancers identified in extensive researches. Abnormal mutations in PER genes can influence cell function, metabolic activity, immunity, and therapy responses, thereby promoting the initiation and development of cancers. This ultimately results in unequal cancers progression and prognosis in patients. This leads to variable cancer progression and prognosis among patients. In-depth studies on the interactions between the PER genes and cancers can reveal novel strategies for cancer detection and treatment. In this review, we aim to provide a comprehensive overview of the latest research on the role of the PER gene family in cancer.

Network Analysis of Osteoarthritis Progression Using a Steiner Minimal Tree Algorithm.

Purpose: To provide a comprehensive analysis of associated genes with osteoarthritis (OA). Here, we reported a network analysis of OA progression by using a Steiner minimal tree algorithm. Methods: We collected the OA-related genes through screening the publications in MEDLINE. We performed functional analysis to analyze the associated biochemical pathways of the OA-related genes. Pathway crosstalk analysis was constructed to explore interactions of the enriched pathways. Steiner minimal tree algorithm was used to analyze molecular pathway networks. The average clustering coefficient was compared with the corresponding values of the Osteoarthritis-specific network. The new finding RNA was compared with former single-cell RNA-seq analysis results. Results: A gene set with 177 members reported to be significantly associated with Osteoarthritis was collected from 187 studies. Functional enrichment analysis revealed a specific related-OA gene including skeletal system development, cytokine-mediated signaling pathway, inflammatory response, cartilage development, and extracellular matrix organization. We performed a pathway crosstalk analysis among the 72 significantly enriched pathways. A total of 151 of the 177 genes in the Osteoarthritis gene set were included in the human interactome network. There were 31 genes in the former single-cell RNA-seq analysis results. The CLU, ENO1, SRRM1, UBC, HMGB1, NR3C1, NOTCH2NL, and CBX5 have significantly increased expression in seven molecularly defined populations of OA cartilage. Conclusion: The Steiner tree-based approach finds new biological molecules associated with OA genes.

Identification of circadian clock-related immunological prognostic index and molecular subtypes in prostate cancer.

BACKGROUND: Evidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). METHODS: PCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis. RESULTS: TOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients. CONCLUSIONS: In this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice.