Circular RNA circATP9A promotes non-small cell lung cancer progression by interacting with HuR and by promoting extracellular vesicles-mediated macrophage M2 polarization.

BACKGROUND: CircRNA is recognized for its significant regulatory function across various cancers. However, its regulatory role in non-small cell lung cancer (NSCLC) is still largely uncharted. METHODS: Analysis based on public databases is completed using R software. circATP9A was identified by two circRNA datasets of NSCLC from the Gene Expression Omnibus database. To examine the impact of circATP9A on the phenotype of NSCLC, we conducted both in vitro and in vivo functional experiments. The mRNA and protein levels of specific molecules were determined through quantitative real-time PCR and western blot assays. RNA pulldown and RNA immunoprecipitation assays were performed to verify the interaction between RNA and protein. The functional role of extracellular vesicles (EVs)-circATP9A on tumor-associated macrophage (TAM) polarization was assessed using co-culture system and cell flow cytometry. RESULTS: Here, we elucidates the functional role of circATP9A in NSCLC. We demonstrated that circATP9A can foster the progression of NSCLC through in vivo and in vitro experiments. From a mechanistic standpoint, circATP9A can interact with the HuR protein to form an RNA-protein complex, subsequently amplifying the mRNA and protein levels of the target gene NUCKS1. Further, the PI3K/AKT/mTOR signaling was identified as the downstream pathways of circATP9A/HuR/NUCKS1 axis. More notably, hnRNPA2B1 can mediate the incorporation of circATP9A into EVs. Subsequently, these EVs containing circATP9A induce the M2 phenotype of TAMs, thereby facilitating NSCLC development. CONCLUSIONS: Our discoveries indicate that circATP9A could serve as a promising diagnostic indicator and a therapeutic target for NSCLC.

Prognostic value of E­26 transformation­specific­related gene in prostate cancer based on immunohistochemistry analysis.

E-26 transformation-specific-related gene (ERG) has been implicated in prostate cancer; however, its prognostic role remains unclear. Therefore, the present study aimed to investigate the association of ERG with the prognosis after radical prostatectomy in patients with prostate cancer. Patient data were collected at the Huadong Hospital, affiliated with Fudan University, between January 2016 and March 2020. ERG protein expression was detected using immunohistochemistry. Independent-sample t-tests and χ2 tests were used to evaluate prostate cancer prognosis depending on ERG levels. The Kaplan-Meier method was used to estimate biochemical failure-free survival (BFFS) and the log-rank test was used to test the distribution. Prognostic factors were determined using Cox regression analysis. The median patient age was 69 years (range, 47-82 years). The median prostate-specific antigen (PSA) and free-PSA levels before treatment were 9.58 ng/ml (range, 0.003-187.400 ng/ml) and 1.13 ng/ml (range, 0.0059-30.6100 ng/ml), respectively. ERG protein expression was positive in 43 (16.6%) and negative in 216 (83.4%) cases. The median follow-up period and BFFS were 30 and 28 months, respectively. There was a significant difference in biochemical recurrence (P=0.017) between patients with positive and negative ERG expression. Patients with positive ERG expression had significantly worse BFFS curves compared with those with negative ERG expression (P=0.0038). In the multivariate Cox regression analysis, positive ERG expression was found to be an independent prognostic factor in patients with prostate cancer who underwent radical prostatectomy (hazard ratio, 4.08; 95% confidence interval, 2.03-8.17; P=0.000074). In conclusion, positive ERG expression is an independent prognostic risk factor for prostate cancer. These findings may be valuable for improvements in the clinical application of ERG immunohistochemistry.

Integrative analysis of tertiary lymphoid structures and immune microenvironment in patients with esophageal carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common upper gastrointestinal malignancies worldwide. Tertiary lymphoid structures (TLS) are tumor-infiltrating immune cells aggregates coupled with stromal cells which are similar to secondary lymphoid organs. The objective of this study is to explore the predictive effects of two common genes associated with TLS models on prognosis and immunotherapy effects in ESCC patients. METHODS: Clinical information for ESCC patients in the TCGA(The Cancer Genome Altas) cohort and GSE 53625 were collected. All of the samples were classified as either high score group or low score group based on two TLS signatures, and the association between TLS signatures and survival, clinical indicators, genomic burden, stemness indices analysis, tumor microenvironment and immunotherapy response were performed. Furthermore, the mature TLS was also assessed in ESCC tissue microarray. RESULTS: In our study, we quantified the score of TLS_9 and TLS_12, respectively, reflecting the different statuses of TLS (TLS_9 = B and T cells in TLSs; TLS_12 = neogenesis of TLSs). Subsequently, we explored the effect of TLS score on ESCC tumor microenvironment quantified by multiple algorithms. We found that a correlation analysis indicated that TLS_9 and TLS_12 were all positively correlated with CD8+ T cell, NK cells, CD4+ T cells, M1 macrophages and so on. Meanwhile, some cells present a different correlation pattern of TLS_9 and TLS_12, including activated CD4+ memory T cells and Tgd cells. Immune-related analysis revealed that the TLS_12 and TLS_9 scores were all positively correlated with immune dysfunction, yet negatively correlated with immune exclusion. Following this, the biological roles of TLS_9 and TLS_12 scores were investigated. Also, we noticed that the TLS score could significantly affect the CAFs infiltration and be associated with the genomic burden and tumor stemness. In addition, we explored the prognostic value of mature TLS through tissue microarray (TMA). Our result displayed ESCC patients with the presence of mature TLS had a better prognosis than ESCC patients without it. CONCLUSIONS: Our study indicated that ESCC patients with the presence of TLS had better outcomes and an inflamed immune microenvironment. In addition, both TLS-9 and TLS-12 gene signatures could be used as potential biomarkers for the immunotherapy of ESCC patients.

Long-term prognosis and prognostic factors of brachytherapy and propensity score matched comparisons of the outcomes between brachytherapy and radical prostatectomy: a retrospective cohort study.

Background: To report outcomes of patients undergoing brachytherapy (BT), investigate factors associated with biochemical progression-free survival (bPFS) and to compare its long-term prognosis with that of radical prostatectomy (RP) in localized prostate cancer. Methods: The clinical data of 87 elderly patients with localized prostate cancer who underwent BT at Huadong Hospital affiliated to Fudan University from January 2009 to December 2016 were retrospectively analyzed. Patient prognoses and associated factors were investigated using univariate and multivariate Cox regression models. The clinical data of the 142 patients with localized prostate cancer who underwent RP during the same period were also collected. By using propensity score matching (PSM), the 42 patients who underwent BT were matched to 42 patients who underwent RP, and the differences in the survival curves were investigated using the Kaplan-Meier method. Results: The median follow-up period of the patients who underwent BT was 101 months. The 5- and 10-year overall survival (OS) rates of the patients who underwent BT were 82.8% and 64.0%, respectively, while the 5- and 10-year bPFS rates were 97.2% and 87.5%, respectively. The preoperative clinical Tumor (T) stage was identified as a prognostic factor of bPFS, as patients who underwent BT whose clinical stage was T3 had a worse prognosis than those whose clinical stage was T1-T2 (HR =0.097, P=0.049). After PSM, the average follow-up time of the BT group was 90 months and that of the RP group was 94 months. No significant differences in bPFS or cause-specific survival were observed between the 2 groups. The OS of the RP group was significantly higher than that of the BP group (P=0.030). Among the patients with a prostate volume >35 mL, those who underwent BT had significantly higher pPFS than those who underwent RP (P=0.041). Conclusions: In the localized prostate cancer, BT and RP offered similar oncological control in the localized prostate cancer. Stage T3 prostate cancer who undergo BT was associated with worse biochemical failure and was the only variable significantly predictive of biochemical recurrence.