A urine extracellular vesicle lncRNA classifier for high-grade prostate cancer and increased risk of progression: A multi-center study.

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n = 350), two independent cohorts (n = 232; n = 251), and TCGA cohort (n = 499). In the prospective active surveillance cohort (n = 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

Targeting extracellular matrix through phytochemicals: a promising approach of multi-step actions on the treatment and prevention of cancer.

Extracellular matrix (ECM) plays a pivotal and dynamic role in the construction of tumor microenvironment (TME), becoming the focus in cancer research and treatment. Multiple cell signaling in ECM remodeling contribute to uncontrolled proliferation, metastasis, immune evasion and drug resistance of cancer. Targeting trilogy of ECM remodeling could be a new strategy during the early-, middle-, advanced-stages of cancer and overcoming drug resistance. Currently nearly 60% of the alternative anticancer drugs are derived from natural products or active ingredients or structural analogs isolated from plants. According to the characteristics of ECM, this manuscript proposes three phases of whole-process management of cancer, including prevention of cancer development in the early stage of cancer (Phase I); prevent the metastasis of tumor in the middle stage of cancer (Phase II); provide a novel method in the use of immunotherapy for advanced cancer (Phase III), and present novel insights on the contribution of natural products use as innovative strategies to exert anticancer effects by targeting components in ECM. Herein, we focus on trilogy of ECM remodeling and the interaction among ECM, cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), and sort out the intervention effects of natural products on the ECM and related targets in the tumor progression, provide a reference for the development of new drugs against tumor metastasis and recurrence.

Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer.

BACKGROUND: We aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: In total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort (n = 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I, n = 183; Cohort II, n = 166). RESULTS: We developed a five-circRNA signature, based on circCEP112, circFAM13A, circBRWD1, circVPS13C and circMACROD2, which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts (P < 0.0001, P < 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores. CONCLUSION: This five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone.

Influence of beamlet width on dynamic IMRT plan quality in nasopharyngeal carcinoma.

Objective: This study aimed to identify the effects of beamlet width on dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) and determine the optimal parameters for the most effective radiotherapy plan. Methods: This study evaluated 20 patients with NPC were selected for dynamic IMRT. Only the beamlet width in the optimization parameters was changed (set to 2, 4, 6, 8, and 10 mm that were named BL02, BL04, BL06, BL08, and BL10, respectively) to optimize the results of the five groups of plans. Using the plan quality scoring system, the dose results of the planning target volumes (PTVs) and organs at risks (OARs) were analyzed objectively and comprehensively. The lower the quality score, the better the quality of the plan. The efficiency and accuracy of plan execution were evaluated using monitor units (MUs) and plan delivery time (PDT). Results: The BL04 mm group had the lowest quality score for the targets and OARs (0.087), while the BL10 mm group had the highest total score (1.249). The BL04 mm group had the highest MUs (837 MUs) and longest PDT (358 s). However, the MUs range of each group plan was below 100 MUs, and the PDT range was within 30 s. In the BL02, BL04, BL06, BL08, and BL10 plans, <5 MUs segments accounted for 33%, 16%, 24%, 33%, and 40% of total segments, respectively, with which the lowest was in the BL04 mm group. Conclusion: Smaller beamlet widths have not only reduced OARs dose while maintaining high dose coverage to the PTVs, but also lead to more MUs that would produce greater PDT. Considering the quality and efficiency of dynamic IMRT, the beamlet width value of the Monaco treatment planning system set to 4 mm would be optimal for NPC.

CircSCAF8 promotes growth and metastasis of prostate cancer through the circSCAF8-miR-140-3p/miR-335-LIF pathway.

Circular RNAs (circRNAs) have been increasingly linked to cancer progression. However, the detailed biological functions of circRNAs in prostate cancer (PCa) remain unclear. Using high-throughput circRNA sequencing, we previously identified 18 urine extracellular vesicle circRNAs that were increased in patients with PCa compared with those with benign prostatic hyperplasia. Spearman correlation analysis of the expression levels of the 18 circRNAs between the tumor tissue and matched urine extracellular vesicles in 30 PCa patients showed that circSCAF8 had the highest R2 (R2 = 0.635, P < 0.001). The Cox proportional hazards regression model was used to estimate the effect of circSCAF8 on progression-free survival. The in vitro and in vivo functional experiments were implemented to investigate the effects of circSCAF8 on the phenotype of PCa. We found that the knockdown of circSCAF8 in PCa cells suppressed the proliferation, migration, and invasion ability, while overexpression of circSCAF8 had the opposite effects. Similar results were observed in vivo. In a cohort of 85 patients who had undergone radical prostatectomy, circSCAF8 expression in PCa tissues was a powerful predictor of progression-free survival (HR = 2.14, P = 0.022). Mechanistically, circSCAF8 can function by binding to both miR-140-3p and miR-335 to regulate LIF expression and activate the LIF-STAT3 pathway that leads to the growth and metastasis of PCa. Collectively, our findings demonstrate that circSCAF8 contributes to PCa progression through the circSCAF8-miR-140-3p/miR-335-LIF pathway.

Acupuncture and moxibustion for cancer-related psychological disorders: A protocol for systematic review and meta-analysis.

INTRODUCTION: Cancer-related psychological disorders (CRPD) with high incidence are often underdiagnosed and undertreated. Although, some studies suggested that acupuncture and moxibustion (AM) are effective and safe for CRPD, lacking strong evidence, for instance, the relevant systematic review, meta-analysis, and randomized control trial (RCT) of a large sample, multicenter, makes the effects and safety remain uncertain. The aim of protocol is to evaluating the RCTs of AM for CRPD to verify the association of AM with the improvement of CRPD. METHODS AND ANALYSIS: Eight electric databases (4 English databases and 4 Chinese databases) will be searched from inception to Mar. 2022. There will be no restrictions on the category of the language. The RCTs of AM for CRPD unlimited to any type of cancer will be included. Depression and anxiety scores will be the primary outcome indicators. Two researchers will independently complete study selection, evaluate the risk of bias, and extract the data. The RevMan 5.2 software will be used to conduct data synthesis using the random-effects model. The weighted mean differences or standardized mean differences with 95% CIs will be used to present the results of measurement data, and the risk ratios with 95% CIs will be used to express the counting data. Additionally, we will use the Grading of Recommendations Assessment, Development, and Evaluation to assess evidence quality. MAIN RESULTS: The results of the meta-analysis will be presented with tables and figures. ETHICS AND DISSEMINATION: The results of this meta-analysis and meta-regression will be disseminated via publication in peer-reviewed journals and will be published at relevant conferences. The data to be used will not contain individual patient data; therefore, there is no need to worry about patient privacy. PROSPERO REGISTRATION NUMBER: CRD42020177219.

Promoter variation in a homeobox gene, CpDll, is associated with deeply lobed leaf in Cucurbita pepo L.

KEY MESSAGE: CpDll, encoding an HD-Zip I transcription factor, positively regulates formation of deeply lobed leaf shape in zucchini, Cucurbita pepo, which is associated with sequence variation in its promoter region. Leaf shape is an important horticultural trait in zucchini (Cucurbita pepo L.). Deeply lobed leaves have potential advantages for high-density planting and hybrid production. However, little is known about the molecular basis of deeply lobed leaf formation in this important vegetable crop. Here, we conducted QTL analysis and fine mapping of the deeply lobed leaf (CpDll) locus using recombinant inbred lines and large F2 populations developed from crosses between the deeply lobed leaf HM-S2, and entire leaf Jin-GL parental lines. We show that CpDll exhibited incomplete dominance for the deeply lobed leaf shape in HM-S2. Map-based cloning provided evidence that CpCll encodes a type I homeodomain (HD)- and Leu zipper (Zip) element-containing transcription factor. Sequence analysis between HM-S2 and Jin-GL revealed no sequence variations in the coding sequences, whereas a number of variations were identified in the promoter region between them. DUAL-LUC assays revealed significantly stronger promoter activity in HM-S2 than that in Jin-GL. There was also significantly higher expression of CpDll in the leaf base of deeply lobed leaves of HM-S2 compared with entire leaf Jin-GL. Comparative analysis of CpDll gene homologs in nine cucurbit crop species (family Cucurbitaceae) revealed conservation in both structure and function of this gene in regulation of deeply lobed leaf formation. Our work provides new insights into the molecular basis of leaf lobe formation in pumpkin/squash and other cucurbit crops. This work also facilitates marker-assisted selection for leaf shape in zucchini breeding.

A urine extracellular vesicle circRNA classifier for detection of high-grade prostate cancer in patients with prostate-specific antigen 2-10 ng/mL at initial biopsy.

The aim of this study was to identify a urine extracellular vesicle circular RNA (circRNA) classifier that could detect high-grade prostate cancer (PCa) of Grade Group (GG) 2 or greater. For this purpose, we used RNA sequencing to identify candidate circRNAs from urinary extracellular vesicles from 11 patients with high-grade PCa and 11 case-matched patients with benign prostatic hyperplasia. Using ddPCR in a training cohort (n = 263), we built a urine extracellular vesicle circRNA classifier (Ccirc, containing circPDLIM5, circSCAF8, circPLXDC2, circSCAMP1, and circCCNT2), which was evaluated in two independent cohorts (n = 497, n = 505). Ccirc showed higher accuracy than two standard of care risk calculators (RCs) (PCPT-RC 2.0 and ERSPC-RC) in both the training cohort and the validation cohorts. In all three cohorts, this novel urine extracellular vesicle circRNA classifier plus RCs was statistically more predictive than RCs alone for predicting ≥ GG2 PCa. This assay, which does not require precollection digital rectal examination nor special handling, is repeatable, noninvasive, and can be easily implemented as part of the basic clinical workflow.

Prospective validation of DACH2 as a novel biomarker for prediction of metastasis and prognosis in muscle-invasive urothelial carcinoma of the bladder.

Metastasis is the main cause of death from muscle-invasive urothelial carcinoma of the bladder (UCB), and the metastatic potential of tumors is often unpredictable. The role of Dachshund homolog 2 gene (DACH2) in tumorigenesis remains unexplored. We aimed to investigate whether DACH2 can be used as a biomarker to predict metastasis and prognosis of muscle-invasive UCB in a sequential training and validation fashion. For the training set (n = 40), compared with UCB patients without lymph node (LN) metastasis, both DACH2 protein and mRNA expression were greatly increased in case-matched patients with LN metastasis. For the independent validation set (n = 243), patients with primary UCB that did not express DACH2 had a longer metastasis-free survival (MFS) and overall survival (OS) than did those with tumors expressing DACH2 (5-year MFS: 88% [95% CI 80-96] versus 19% [95% CI 7-31], p < 0.001; 5-year OS: 93% [95% CI 87-99] versus 37% [95% CI 23-51], p < 0.001). Multivariable analysis of DACH2 status showed hazard ratios of 7.34 (95% CI 3.15-11.87, p < 0.001) for MFS and 3.96 (95% CI 2.04-7.16, p < 0.001) for OS which were much higher than hazard ratios associated with other independent risk factors. Collectively, DACH2 is an independent prognostic marker that can be used at initial diagnosis of UCB to identify patients who have a high potential to develop metastasis.