Genome-wide identification and analysis of epithelial-mesenchymal transition-related RNA-binding proteins and alternative splicing in a human breast cancer cell line.

Exploring the mechanism of breast cancer metastasis and searching for new drug therapeutic targets are still the focuses of current research. RNA-binding proteins (RBPs) may affect breast cancer metastasis by regulating alternative splicing (AS) during epithelial-mesenchymal transition (EMT). We hypothesised that during EMT development in breast cancer cells, the expression level of RBPs and the gene AS pattern in the cell were significantly changed on a genome-wide scale. Using GEO database, this study identified differentially expressed RBPs and differential AS events at different stages of EMT in breast cancer cells. By establishing the correlation network of differential RBPs and differential AS events, we found that RBM47, PCBP3, FRG1, SRP72, RBMS3 and other RBPs may regulate the AS of ITGA6, ADGRE5, TNC, COL6A3 and other cell adhesion genes. By further analysing above EMT-related RBPs and AS in breast cancer tissues in TCGA, it was found that the expression levels of ADAT2, C2orf15, SRP72, PAICS, RBMS3, APOBEC3G, NOA1, ACO1 and the AS of TNC and COL6A3 were significantly correlated with the prognosis of breast cancer patients. The expression levels of all 8 RBPs were significantly different in breast cancer tissues without metastasis compared with normal breast tissues. Conclusively, eight RBPs such as RBMS3 and AS of TNC and COL6A3 could be used as predictors of breast cancer prognosis. These findings need to be further explored as possible targets for breast cancer treatment.

ICBP90, an epigenetic regulator, induces DKK3 promoter methylation, promotes glioma progression, and reduces sensitivity to cis-platinum.

Glioma is the most common brain malignancy, characterized by high morbidity, high mortality, and treatment-resistance. Inverted CCAAT box Binding Protein of 90 kDa (ICBP90) has been reported to be involved in tumor progression and the maintenance of DNA methylation. Herein, we constructed ICBP90 over-expression and knockdown glioma cell lines, and found that ICBP90 knockdown inhibited glioma cell proliferation, migration, and invasion. ICBP90 silencing potentially enhanced cellular sensitivity to cis-platinum (DDP) and exacerbated DDP-induced pyroptosis, manifested by the elevated levels of gasdermin D-N-terminal and cleaved caspase 1; whereas, ICBP90 over-expression exhibited the opposite effects. Consistently, ICBP90 knockdown inhibited tumor growth in an in vivo mouse xenograft study using U251 cells stably expressing sh-ICBP90 and oe-ICBP90. Further experiments found that ICBP90 reduced the expression of Dickkopf 3 homolog (DKK3), a negative regulator of ß-catenin, by binding its promoter and inducing DNA methylation. ICBP90 knockdown prevented the nuclear translocation of ß-catenin and suppressed the expression of c-Myc and cyclin D1. Besides, DKK3 over-expression restored the effects of ICBP90 over-expression on cell proliferation, migration, invasion, and DDP sensitivity. Our findings suggest that ICBP90 inhibits the expression of DKK3 in glioma by maintaining DKK3 promoter methylation, thereby conducing to ICBP90-mediated carcinogenesis and drug insensitivity.

Prediction of Recurrent Cervical Cancer in 2-Year Follow-Up After Treatment Based on Quantitative and Qualitative Magnetic Resonance Imaging Parameters: A Preliminary Study.

PURPOSE: This study investigated predictors of cervical cancer (CC) recurrence from native T1 mapping, conventional imaging, and clinicopathologic metrics. PATIENTS AND METHODS: In total, 144 patients with histopathologically confirmed CC (90 with and 54 without surgical treatment) were enrolled in this prospective study. Native T1 relaxation time, conventional imaging, and clinicopathologic characteristics were acquired. The association of quantitative and qualitative parameters with post-treatment tumor recurrence was assessed using univariate and multivariate Cox proportional hazard regression analyses. Independent risk factors were combined into a model and individual prognostic index equation for predicting recurrence risk. The receiver operating characteristic (ROC) curve determined the optimal cutoff point. RESULTS: In total, 12 of 90 (13.3%) surgically treated patients experienced tumor recurrence. Native T1 values (X1) [hazard ratio (HR) 1.008; 95% confidence interval (CI) 1.001-1.016], maximum tumor diameter (X2) (HR 1.065; 95% CI 1.020-1.113), and parametrial invasion (X3) (HR 3.930; 95% CI 1.013-15.251) were independent tumor recurrence risk factors. The individual prognostic index (PI) of the established recurrence risk model was PI = 0.008X1 + 0.063X2 + 1.369X3. The area under the ROC curve (AUC) of the Cox regression model was 0.923. A total of 20 of 54 (37.0%) non-surgical patients experienced tumor recurrence. Native T1 values (X1) (HR 1.012; 95% CI 1.007-1.016) and lymph node metastasis (X2) (HR 4.064; 95% CI 1.378-11.990) were independent tumor recurrence risk factors. The corresponding PI was calculated as follows: PI = 0.011X1 + 1.402X2; the Cox regression model AUC was 0.921. CONCLUSIONS: Native T1 values combined with conventional imaging and clinicopathologic variables could facilitate the pretreatment prediction of CC recurrence.

Risk factors for the recurrence of cervical cancer using MR-based T1 mapping: A pilot study.

Objectives: This study aimed to identify risk factors for recurrence in patients with cervical cancer (CC) through quantitative T1 mapping. Methods: A cohort of 107 patients histopathologically diagnosed with CC at our institution between May 2018 and April 2021 was categorized into surgical and non-surgical groups. Patients in each group were further divided into recurrence and non-recurrence subgroups depending on whether they showed recurrence or metastasis within 3 years of treatment. The longitudinal relaxation time (native T1) and apparent diffusion coefficient (ADC) value of the tumor were calculated. The differences between native T1 and ADC values of the recurrence and non-recurrence subgroups were analyzed, and receiver operating characteristic (ROC) curves were drawn for parameters with statistical differences. Logistic regression was performed for analysis of significant factors affecting CC recurrence. Recurrence-free survival rates were estimated by Kaplan-Meier analysis and compared using the log-rank test. Results: Thirteen and 10 patients in the surgical and non-surgical groups, respectively, showed recurrence after treatment. There were significant differences in native T1 values between the recurrence and non-recurrence subgroups in the surgical and non-surgical groups (P<0.05); however, there was no difference in ADC values (P>0.05). The areas under the ROC curve of native T1 values for discriminating recurrence of CC after surgical and non-surgical treatment were 0.742 and 0.780, respectively. Logistic regression analysis indicated that native T1 values were risk factors for tumor recurrence in the surgical and non-surgical groups (P=0.004 and 0.040, respectively). Compared with cut-offs, recurrence-free survival curves of patients with higher native T1 values of the two groups were significantly different from those with lower ones (P=0.000 and 0.016, respectively). Conclusion: Quantitative T1 mapping could help identify CC patients with a high risk of recurrence, supplementing information on tumor prognosis other than clinicopathological features and providing the basis for individualized treatment and follow-up schemes.

Intraoperative radiotherapy versus no radiotherapy for early stage low-risk breast cancer patients undergoing breast-conserving surgery: a propensity score matching study based on the SEER database

Purpose To compare the effect of intraoperative radiotherapy (IORT) and no radiotherapy in early stage low-risk breast cancer patients undergoing breast-conserving surgery. Methods According to the criteria recommended by ASTRO for patients eligible for IORT, we retrospectively selected women with early stage low-risk breast cancer who underwent breast-conserving surgery from 2010 to 2019 from the SEER database. Propensity score matching was used to balance the differences in baseline characteristics. The Kaplan–Meier method was used to calculate the overall survival (OS) and breast cancer-specific survival (BCSS) of patients, and the log-rank test was used to compare the differences. Results A total of 20,245 patients were included in the analysis, including 1738 in the IORT group and 18,507 in the no radiotherapy group, with a median follow-up of 41 months. Before matching, the 5-year OS rates of the IORT group and the no radiotherapy group were 95.5% and 85.7% (p < 0.001), respectively, and the 5-year BCSS rates of the two groups were 99.6% and 98.3% (p < 0.001), respectively. After matching, the 5-year OS rates were 95.6% and 90.3% (p < 0.001) in the IORT group and the no radiotherapy group, respectively, and the 5-year BCSS rates were 99.5% and 99.1% (p = 0.028), respectively. Cox multivariate analysis of the original data showed that radiotherapy was an independent prognostic factor for both OS and BCSS (p < 0.05). Conclusions For patients aged 50 years or older with early stage low-risk breast cancer, IORT may be a better option, with improved BCSS compared to the elimination of radiotherapy. The study could not draw conclusions on OS, because underlying diseases may be unevenly distributed between the two groups (AU)

Intraoperative radiotherapy versus no radiotherapy for early stage low-risk breast cancer patients undergoing breast-conserving surgery: a propensity score matching study based on the SEER database.

PURPOSE: To compare the effect of intraoperative radiotherapy (IORT) and no radiotherapy in early stage low-risk breast cancer patients undergoing breast-conserving surgery. METHODS: According to the criteria recommended by ASTRO for patients eligible for IORT, we retrospectively selected women with early stage low-risk breast cancer who underwent breast-conserving surgery from 2010 to 2019 from the SEER database. Propensity score matching was used to balance the differences in baseline characteristics. The Kaplan-Meier method was used to calculate the overall survival (OS) and breast cancer-specific survival (BCSS) of patients, and the log-rank test was used to compare the differences. RESULTS: A total of 20,245 patients were included in the analysis, including 1738 in the IORT group and 18,507 in the no radiotherapy group, with a median follow-up of 41 months. Before matching, the 5-year OS rates of the IORT group and the no radiotherapy group were 95.5% and 85.7% (p < 0.001), respectively, and the 5-year BCSS rates of the two groups were 99.6% and 98.3% (p < 0.001), respectively. After matching, the 5-year OS rates were 95.6% and 90.3% (p < 0.001) in the IORT group and the no radiotherapy group, respectively, and the 5-year BCSS rates were 99.5% and 99.1% (p = 0.028), respectively. Cox multivariate analysis of the original data showed that radiotherapy was an independent prognostic factor for both OS and BCSS (p < 0.05). CONCLUSIONS: For patients aged 50 years or older with early stage low-risk breast cancer, IORT may be a better option, with improved BCSS compared to the elimination of radiotherapy. The study could not draw conclusions on OS, because underlying diseases may be unevenly distributed between the two groups.

MRI-visible enlarged perivascular spaces: imaging marker to predict cognitive impairment in older chronic insomnia patients.

OBJECTIVE: Perivascular spaces (PVS), components of the glymphatic system in the brain, have been known to be important conduits for clearing metabolic waste, and this process mainly increases during sleep. Sleep disruption might result in PVS dysfunction and cognitive impairment. In this study, we aim to explore whether MRI-visible enlarged perivascular spaces (EPVS) could be imaging markers to predict cognitive impairment in chronic insomnia patients. METHOD: We obtained data from 156 patients with chronic insomnia and 79 age-matched healthy individuals. Using T2-weighted MRI images, visible EPVS in various brain regions were measured and analyzed. The associations between EPVS numbers and cerebrospinal fluid (CSF) ß-amyloid 42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) level in chronic insomnia patients were evaluated. RESULT: Our results showed that MRI-visible EPVS in the frontal cortex, centrum semiovale, basal ganglia, and hippocampus of chronic insomnia patients with impaired cognition (ICG) significantly increased than that in normal cognition (NCG) patients. The increased MRI-visible EPVS in the frontal cortex, centrum semiovale, and basal ganglia were also associated with the increased CSF Aß42, t-tau, and p-tau level in ICG patients. MRI-visible EPVS in the basal ganglia and centrum semiovale had high sensitivity and specificity in distinguishing ICG chronic insomnia patients from those with NCG. CONCLUSION: Our study indicated that MRI-visible EPVS in the basal ganglia and centrum semiovale might be valuable imaging markers to predict cognitive impairment in chronic insomnia patients. It will be meaningful to discern those cognitive decline patients in preclinical stage and take some measures to prevent disease progression. KEY POINTS: • Increased MRI-visible EPVS were associated with the increased CSF Aß42, t-tau, and p-tau level in older chronic insomnia patients with impaired cognition.

Identification of low-dose radiation-induced exosomal circ-METRN and miR-4709-3p/GRB14/PDGFRα pathway as a key regulatory mechanism in Glioblastoma progression and radioresistance: Functional validation and clinical theranostic significance.

Glioblastoma is a central nervous malignancy with a very poor prognosis. This study attempted to explore the role of exosomes induced by low-dose radiation-induced (ldrEXOs) and ldrEXOs-derived circ-METRN in glioblastoma progression and radioresistance at the molecular, cellular, animal, and clinical levels. Results in the present study revealed that low-dose radiation stimulated the secretion of ldrEXOs which delivered high levels of circ-METRN. And circ-METRN-abundant ldrEXOs increased the expression of γ-H2AX, indicating an efficient DNA damage-repair process in glioblastoma cells. The ldrEXOs-derived circ-METRN enhanced the glioblastoma progression and radioresistance via miR-4709-3p/GRB14/PDGFRα pathway. Up-regulating PDGFRα can rescue the tumor-promoting function of ldrEXOs in groups previously treated with inhibition of GRB14. Additionally, in-vivo experiments revealed that treatments with ldrEXOs promoted the growth of xenografted tumors and shortened the survival period. Furthermore, clinical researches indicated that circ-METRN may be transported into the bloodstream by exosomes in the early stages of fractionated radiotherapy. It has important clinical values to detect the serum exosomal circ-METRN in the early stage of radiotherapy, which is not only conducive to predict radioresistance and prognosis but also to assist MRI diagnosis in detecting the very early recurrence of glioblastoma. In summary, this study reveals for the first time that low-dose radiation-induced exosomal circ-METRN plays an oncogenic role in glioblastoma progression and radioresistance through miR-4709-3p/GRB14/PDGFRα pathway, providing mechanistic insights into the roles of circRNAs and a valuable marker for therapeutic targets in glioblastoma.

Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson's disease.

Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease (PD). However, there is no direct evidence in humans to support this role1-5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD.

Targeted Intraoperative Radiotherapy Is Non-inferior to Conventional External Beam Radiotherapy in Chinese Patients With Breast Cancer: A Propensity Score Matching Study.

Purpose: To investigate the efficacy of targeted intraoperative radiotherapy (TARGIT) vs. conventional external beam radiotherapy (EBRT) in Chinese patients with breast cancer. Methods: We retrospectively analyzed breast cancer patients who underwent breast-conserving surgery (BCS) at our hospital between April 2009 and October 2017. Patients were divided into TARGIT group and EBRT group according to different radiotherapy methods. TARGIT was performed with low-energy X-rays emitted by the Intrabeam system to deliver a single dose of 20 Gy to the applicator surface. Propensity score matching was performed at 1:1. The Kaplan-Meier method was used to calculate the locoregional recurrence (LR), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) of the two groups, and the log-rank test was run to analyse between-group difference before and after matching. Results: A total of 281 patients were included, with a median follow-up of 43 months. Of them, 82 were included in the TARGIT group and 199 in the EBRT group. Using the risk-adapted approach, 6.1% of patients received supplemental EBRT in the TARGIT group. The 5-year LR rate was 3.2% in the TARGIT group and 3.1% in the EBRT group (P = 0.694), the 5-year DMFS rates were 100 and 96.7%, respectively (P = 0.157); the 5-year DFS rates were 96.8 and 94.2% (P = 0.604); and the 5-year OS rates were 97.6 and 97.8% (P = 0.862). After matching which eliminated interference from imbalanced baseline factors, 128 matched patients were analyzed by the Kaplan-Meier method. The 5-year LR rate was 2.3% in the TARGIT group and 1.6% in the EBRT group; the 5-year DMFS rates were 100 and 98.4%, respectively; the 5-year DFS rates were 97.7 and 98.4%; and the 5-year OS rates were 98.4 and 98.4% (P = 0.659, 0.313, 0.659, 0.987). There was no significant difference in efficacy between TARGIT group and EBRT group. Conclusion: TARGIT and EBRT have similar 5-year outcomes in selected Chinese breast cancer patients undergoing BCS, and it can be used as an effective alternative to standard therapy, with substantial benefits to patients. The results need to be further confirmed by extending the follow-up time.

Circular METRN RNA hsa_circ_0037251 Promotes Glioma Progression by Sponging miR-1229-3p and Regulating mTOR Expression.

Circular RNAs (circRNAs) are a newly identifed non-coding RNA in many cellular processes and tumours. This study aimed to investigate the role of hsa_circ_0037251, one circRNA generated from several exons of the gene termed METRN, in glioma progression. Through in vitro experiments, we discovered that high expression of hsa_circ_0037251 was related to low expression of the microRNA miR-1229-3p and high expression of mTOR. The over-expressed hsa_circ_0037251 promoted cell proliferation, invasion and migration in glioma, while knockdown of hsa_circ_00037251 promoted cell apoptosis and induced G1 phase arrest. Then, hsa_circ_0037251 was observed to directly sponge miR-1229-3p, and mTOR was identified as a direct target of miR-1229-3p. In addition, knockdown of hsa_circ_0037251 up-regulated the expression of miR-1229-3p and inhibited the expression of mTOR. And overexpression of miR-1229-3p or low-expressed mTOR inhibited the glioma cell progression. Furthermore, transfection with mTOR overexpression vectors can restore the abilities of glioma cell progression even if hsa_circ_00037251 was knocked down using siRNAs. In vivo experiments revealed that hsa_circ_00037251 promoted the growth of xenografted tumours and shortened the survival period. These results indicated that hsa_circ_0037251 may act as a tumour promoter by a hsa_circ_0037251/miR-1229-3p/mTOR axis, and these potential biomarkers may be therapeutic targets for glioma.

Efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy in breast-conserving surgery for early-stage breast cancer: a single-centre study in China.

OBJECTIVE: The purpose of this study was to evaluate the efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy for the treatment of Chinese patients with early-stage breast cancer. METHODS: Between September 2014 and May 2017, breast cancer patients undergoing targeted intraoperative radiotherapy at our facility were retrospectively recruited for this study. Intraoperative radiotherapy was performed with a 50-kV X-ray source in an Intrabeam system (Carl Zeiss Meditec, Oberkochen, Germany). The one-time prescribed irradiation dose to the tumour bed was 20 Gy. Recurrence, death, late complications, and cosmetic outcomes were recorded. Late radiotoxicity was assessed based on the grading criteria of the Radiation Therapy Oncology Group. RESULTS: A total of 77 patients who were treated with targeted intraoperative radiotherapy only were recruited. The cohort had a mean age of 58 years; patients with T1, N0, and invasive ductal carcinoma accounted for 75.3, 89.6, and 84.4%, respectively; the median follow-up duration was 40 months; there were 2 patients of recurrence and 2 patients of death. There were no patients of cardiac toxicity or skin or lung radiotoxicity of grade 2 or above. The main complications were breast oedema (18.2%), seroma (15.6%), chromatosis (9.1%), induration (7.8%), pain (5.2%), skin depression (2.6%), mild dry cough (2.6%), delayed wound healing (1.3%), and wound infection (1.3%). Seventy-three patients participated in the cosmetic outcome evaluation, which yielded an excellent or good rate of 95.9%. CONCLUSIONS: Due to its low recurrence rates, lack of high-grade late radiotoxicity, and excellent cosmetic outcomes, targeted intraoperative radiotherapy may be a suitable treatment for select early-stage breast cancer patients in China.

FOXC1 silencing inhibits the epithelial­to­mesenchymal transition of glioma cells: Involvement of ß­catenin signaling.

Glioma is a type of malignant brain tumor. Forkhead box C1 (FOXC1) is a conserved transcription factor that is involved in tumorigenesis; however, the function of FOXC1 in glioma remains unclear. The present study aimed to investigate the effects of FOXC1 silencing on the epithelial­to­mesenchymal transition (EMT) of glioma cells. FOXC1­specific small interfering RNAs were employed to downregulate the expression levels of FOXC1 in glioma cells. The proliferation, migration and invasion of glioma cells were assessed by MTT assay, wound healing assay and Transwell assay. Western blot analysis was performed to reveal the effects of FOXC1 on EMT­associated proteins and ß­catenin signaling. The results revealed that, following FOXC1 silencing, the proliferation, migration and invasion of glioma cells were decreased. The expression levels of EMT­associated proteins were also affected. Further examination demonstrated that ß­catenin signaling was involved in the effects of FOXC1 on glioma cells. Previous results suggested that overexpression of ß­catenin reversed the effects of FOXC1 silencing on glioma cells. The present study demonstrated that FOXC1 may regulate the EMT of glioma cells, potentially via ß­catenin signaling. Therefore, FOXC1 may be a potential therapeutic target for the treatment of glioma.

Comparisons of skin toxicity in patients with extranodal nasal-type natural killer/T-cell lymphoma after treatment with intensity-modulated radiotherapy and conventional radiotherapy.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) has been more widely used in extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) because it can maximally improve the local control rate of tumor and reduce the radiation dose received by surrounding normal tissues. However, there has been no consensus on whether IMRT can help to lower the toxic and adverse reactions caused by radiation therapy. The aim of this study is to compare skin toxicity caused by IMRT and conventional radiotherapy in Stage I-II NKTCL. METHODS: A total of 93 patients with Stage I-II NKTCL, nasal-type arising in the nasal cavity were consecutively treated using curative radiotherapy between April 2005 and August 2014. These patients received radiotherapy without chemotherapy. Definitive radiotherapy was conducted using conventional radiotherapy in 33 patients and IMRT in the other sixty patients with a regional field and a total dose of 50 Gy. Dosimetric parameters of radiation treatment plans and skin toxicity were analyzed and compared between conventional radiotherapy and IMRT. RESULTS: From the dosimetric analysis, IMRT demonstrated significantly improved dose coverage and homogeneity than conventional radiotherapy. Meanwhile, the Grade 1, 2, and 3 skin toxicity incidences in conventional radiotherapy group were 42.4%, 39.4%, and 18.2%, and in IMRT group were 25.0%, 31.7%, and 43.3%, respectively. Our data suggested that the severity of skin toxicity in IMRT group was statistically higher than that in conventional radiotherapy group. CONCLUSIONS: IMRT provided improved dose coverage than conventional radiotherapy. However, IMRT failed to lower patients' risks for skin toxicity and may have the potential to increase skin toxicity.

Protein N-arginine methyltransferase 5 promotes the tumor progression and radioresistance of nasopharyngeal carcinoma.

Radiotherapy resistance is the main cause of the the poor prognosis of some nasopharyngeal carcinoma (NPC) patients. Yet, the exact mechanism is still elusive. In the present study, we explored the clinical and biological role of protein arginine methyltransferase 5 (PRMT5) in NPC. Our results revealed that PRMT5 was overexpressed in NPC tissues when compared with that in adjacent non-tumor tissues by quantitative RT-PCR and immunoblotting. High expression of PRMT5 was correlated with adverse outcomes of NPC patients as determined by the scoring of a tissue microarray. Silencing of PRMT5 promoted the radiosensitivity of 5-8F and CNE2 cells as determined by cell proliferation and colony formation assays. Furthermore, fibroblast growth factor receptor 3 (FGFR3) was identified as one of the downstream targets of PRMT5, and the silencing of PRMT5 decreased the mRNA and protein levels of FGFR3 in the 5-8F and CNE2 cells. Silencing of FGFR3 induced similar phenotypes as the inhibition of PRMT5, and re-expression of FGFR3 in 5-8F/shPRMT5 and CNE2/shPRMT5 cells restored the proliferation and colony formation ability induced by irradiation exposure. Our results indicate that PRMT5 is a marker of poor prognosis in NPC patients. PRMT5 promoted the radioresistance of NPC cells via targeting FGFR3, at least partly if not totally. PRMT5 and its downstream effector FGFR3 may be potential targets for anticancer strategy.

[Prognostic value of combined expression of Aurora A, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer].

OBJECTIVE: The aim of this study was to investigate the prognostic value of combined expression of Aurora A, Ki-67, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer (NSCLC). METHODS: Expressions of Aurora A, Ki-67, p53 and p21 WAF1 in 58 tumor samples from resected primary NSCLCs were detected by immunohistochemistry. The correlation of proteins, survival and clinicopathological characteristics was analyzed. RESULTS: The positive rates of Aurora A, Ki-67, p53 and p21 WAF1 expression were 89.7% (52/58), 53.4% (31/58), 46.6% (27/58) and 34.5% (20/58), respectively. Aurora A expression was positively correlated with nodal metastasis (69.2% vs. 37.8%, P = 0.045). The univariable analysis showed that the overall survival (OS) was 75.0%in patients with low Aurora A expression and 46.0% in patients with high Aurora A expression (P = 0.039). The 3-year survival rate was 40.0% in patients with positive expression of Aurora A and p53, 65.0% in the patients with positive expression of Aurora A or p53, and 82.1% in the patients with negative expression of Aurora A and p53 (P = 0.039). The Cox regression model showed that combined expression of Aurora and p53 is an independent factor affecting the prognosis of NSCLC patients (P = 0.015). CONCLUSIONS: Our findings suggest that the positive expression of Aurora A, Ki-67 and p53 proteins is an unfavorable factor affecting the prognosis for NSCLC patients, and the overexpression of Aurora A is an independent unfavorable factor association with shorter OS in NSCLC patients. Detection of positive Aurora A and p53 expression may be a useful predictive prognostic indicator for NSCLC patients.

Reappraisal of the role of postoperative radiation therapy in patients with pIIIa-N2 non-small cell lung cancer: A propensity score matching analysis.

BACKGROUND: Reappraisal of the role of postoperative radiotherapy in pN2 non-small cell lung cancer (NSCLC) patients according to N1 lymph node involvement. METHODS: A total of 218 pIIIa-N2 NSCLC patients who underwent complete surgical resection with systematic nodal dissections were enrolled. Propensity scores were used for matching N1 involvement. Overall survival (OS) and disease-free survival (DFS) were analyzed retrospectively. RESULTS: After matching, pN2b patients without N1 involvement (pN0N2b) exhibited better prognoses than those with N1 involvement (pN1N2b) (5-year OS: 37.5% vs. 7.1%, P = 0.008; 5-year DFS: 31.8% vs. 4.6%, P = 0.004). Similar results were not detected in pN2a disease (5-year OS: 37.8% vs. 31.0%, P = 0.517; 5-year DFS: 27.1% vs. 20.2%, P = 0.788). The five-year OS of patients who received no adjuvant therapy (22 pN2a cases, 7 pN0N2b, 5 pN1N2b), adjuvant chemotherapy alone (74 pN2a cases, 11 pN0N2b, 17 pN1N2b) or chemoradiotherapy (25 pN2a cases, 7 pN0N2b, 6 pN1N2b) were compared (pN2a: 31.3%, 37.0%, and 32.0%, P = 0.808; pN0N2b: 0.0%, 18.2%, and 71.4%, P = 0.108; pN1N2b: 0.0%, 0.0%, and 33.3%, P < 0.0001). The five-year DFS was also analyzed (pN2a: 31.6%, 24.0%, and 18.3%, P = 0.410; pN0N2b: 0.0%, 11.1%, and 57.1%, P = 0.192; pN1N2b: 0.0%, 0.0%, and 16.7%, P < 0.0001). Multivariate analysis revealed that the novel classification based on N1 involvement and pN2a/pN2b staging was an independent prognostic factor of OS and DFS. CONCLUSION: N1 involvement significantly impacted the prognosis of pN2b NSCLC patients. The benefit of adjuvant therapy in pN2a and pN0N2b patients requires confirmation by further study.

The impact of positive nodal chain ratio on individualized multimodality therapy in non-small-cell lung cancer.

This study aimed to analyze the prognostic significance of the positive nodal chain ratio (NCR) in non-small-cell lung cancer (NSCLC). A total of 208 pIIIa-N2 NSCLC patients who underwent complete surgical resections with a systematic nodal dissection were enrolled. The median values of NCR and the positive lymph node ratio (LNR) were used to grouping patients. The differences of overall survival (OS) and disease-free survival (DFS) between the different groups were compared. The median values of NCR and LNR were 0.31 and 0.45, respectively. The patients were separated into group A (NCR ≤0.45 and LNR ≤0.31; 91 cases), group B (NCR ≤0.45 and LNR >0.31 or NCR >0.45 and LNR ≤0.31; 51 cases), and group C (NCR >0.45 and LNR >0.31; 66 cases) according to their combined LCR and LNR values. Groups A, B, and C exhibited significantly different prognoses (5-year OS: 43.7, 25.2, and 12.3 %, respectively, p < 0.0001; 5-year DFS: 30.4, 23.3, and 8.6 %, respectively, p < 0.0001). Multivariate analyses revealed that this novel grouping method based on the combination of NCR and LNR was an independent prognostic factor for 5-year OS and 5-year DFS in pIIIa-N2 NSCLC. In group C, patients who received no postoperative treatment, adjuvant chemotherapy alone, or chemoradiotherapy exhibited different 5-year OS rates (0.0, 11.6, and 37.5 %, respectively, p = 0.003) and 5-year DFS rates (0.0, 7.5, and 25.0 %, respectively, p = 0.009). Therefore, postoperative chemoradiotherapy may significantly improve the prognosis of patients displaying NCR >0.45 and LNR >0.31. NCR combined with LNR may be more effective to guide individualized multimodality therapy including postoperative chemoradiotherapy for pIIIa-N2 NSCLC.

[Advances in the molecular mechanisms and prognostic significance of EMT in non-small cell lung cancer].

Epithelial to mesenchymal transition (EMT) has an important role in the development of embryo, as well as that in the metastasis of non-small cell lung cancer (NSCLC). Recent researches have demonstrated that both morphological and phenotypic conversions emerge in cells undergoing EMT. As most of relevant studies were on other cancers, it is essential to uncover whether it is the similar mechanisms accounting for EMT in NSCLC. With the progress of the studies, EMT-related basic researches are gradually applied to predicting the prognosis of NSCLC. The aim of this article was to discuss the mechanisms related to EMT emerging in NSCLC.