Background： The prognostic values of staging parameters require continual re-assessment amid changes in diag-nostic and therapeutic methods. This study aimed to identify the prognostic factors and ...failure patterns of non-meta-static nasopharyngeal carcinoma（NPC） in the intensity-modulated radiotherapy（IMRT） era.Methods： We reviewed the data from 749 patients with newly diagnosed, biopsy-proven, non-metastatic NPC in our cancer center（South China, an NPC endemic area） between January 2003 and December 2007. All patients under-went magnetic resonance imaging（MRI） before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log-rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results： The 5-year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5-year survival rates were as follows： local relapse-free survival, 94.6%; nodal relapse-free survival, 97.0%; distant metastasis-free survival, 82.6%; disease-free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac-tor for local failure（P = 0.011）. Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho＇s location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure（all P 〈 0.05）. Intracranial extension had signiicant prognostic value for distant failure（P = 0.040）.Conclusions： The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.
MicroRNAs (miRNAs) regulate gene expression by binding to target sites and initiating translational repression and/or mRNA degradation. In our previous study, we have shown that expression of serum ...microRNA (miR)-21 is correlated with TNM stage and lymph node metastasis and might be an independent prognostic factor for NSCLC patients. However, the roles of miR-21 overexpression in NSCLC development are still unclear. The purpose of this study is to investigate the effect of miR-21 and determine whether miR-21 can be a therapeutic target for human NSCLC.
Taq
man real-time quantitative RT-PCR assay was performed to detect miR-21 expression in NSCLC cell lines and tissues. Next, the effects of miR-21 expression on NSCLC cell characteristics including growth, invasion, and chemo- or radioresistance were also determined. Results showed that miR-21 is commonly upregulated in NSCLC cell lines and tissues with important functional consequences. In addition, we found that anti-miR-21 could significantly inhibit growth, migration and invasion, and reverse chemo- or radioresistance of NSCLC cells, while miR-21 mimics could increase growth, promote migration and invasion, and enhance chemo- or radioresistance of NSCLC cells. Meanwhile, miR-21 mimics could inhibit expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3′-untranslated region (UTR)-based reporter construct in A549 cells, while anti-miR-21 could increase expression of PTEN mRNA and protein and the luciferase activity of a PTEN 3′-UTR-based reporter construct in A549 cells. Furthermore, overexpression of PTEN could mimic the same effects of anti-miR-21 in NSCLC cells, and siRNA-mediated downregulation of PTEN could rescue the effects on NSCLC cells induced by anti-miR-21. Taken together, these results provide evidence to show the promotion role of miR-21 in NSCLC development through modulation of the PTEN signaling pathway.
The identification of cancer-associated long non-coding RNAs and the investigation of their molecular and biological functions are important for understanding the molecular biology and progression of ...cancer. HOTAIR (HOX transcript antisense intergenic RNA) has been implicated in several cancers; however, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of HOTAIR in NSCLC and to evaluate its biological role and clinical significance in tumor progression.
Expression of HOTAIR was analyzed in 42 NSCLC tissues and four NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of HOTAIR. The effect of HOTAIR on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Tail vein injection of cells was used to study metastasis in nude mice. Protein levels of HOTAIR targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed).
HOTAIR was highly expressed both in NSCLC samples and cell lines compared with corresponding normal counterparts. HOTAIR upregulation was correlated with NSCLC advanced pathological stage and lymph-node metastasis. Moreover, patients with high levels of HOTAIR expression had a relatively poor prognosis. Inhibition of HOTAIR by RNAi decreased the migration and invasion of NSCLC cells in vitro and impeded cell metastasis in vivo. HOXA5 levels were affected by HOTAIR knockdown or over-expression in vitro.
Our findings indicate that HOTAIR is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell invasion and metastasis, partially via the down-regulation of HOXA5. Thus, HOTAIR may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention.
Background
The prognosis of patients who have Epstein‐Barr virus (EBV)‐related nasopharyngeal carcinoma (NPC) in which the tumor tissues harbor EBV have a better prognosis than those without ...EBV‐related NPC. Therefore, the eighth edition of the TNM staging system could be modified for EBV‐related NPC by incorporating the measurement of plasma EBV DNA.
Methods
In total, 979 patients with NPC who received intensity‐modulated radiotherapy (IMRT) were retrospectively reviewed. Recursive partitioning analysis was conducted based on tumor (T) classification, lymph node (N) classification, and EBV DNA measurement to derive objectively the proposed stage groupings. The validity of the proposed stage groupings was confirmed in a prospective cohort of 550 consecutive patients who also received with IMRT.
Results
The pretreatment plasma EBV DNA level was identified as a significant, negative prognostic factor for progression‐free survival and overall survival in univariate analysis (all P < .001) and multivariate analysis (all P < .05). Recursive partitioning analysis of the primary cohort to incorporate EBV DNA generated the following proposed stage groupings: stage RI (T1N0), RIIA (T2‐T3N0 or T1‐T3N1, EBV DNA ≤2000 copies/mL), stage RIIB (T2‐T3N0 or T1‐T3N1, EBV DNA >2000 copies/mL; T1‐T3N2, EBV DNA ≤2000 copies/mL), stage RIII (T1‐T3N2, EBV DNA >2000 copies/mL; T4N0‐N2), and stage RIVA (any T and N3). In the validation cohort, the 5‐year progression‐free survival rate was 100%, 87.9%, 76.7%, 68.7%, and 50.4% for proposed stage RI, RIIA, RIIB, RIII, and RIV NPC, respectively (P < .001). Compared with the eighth edition TNM stage groupings, the proposed stage groupings incorporating EBV DNA provided better hazard consistency, hazard discrimination, outcome prediction, and sample size balance.
Conclusions
The proposed stage groupings have better prognostic performance than the eighth edition of the TNM staging system. EBV DNA titers should be included in the TNM staging system to assess patients who have EBV‐related NPC.
The proposed stage groupings incorporating Epstein‐Barr virus DNA by Recursive partitioning analysis have better prognostic performance than the eighth edition American Joint Committee on Cancer/Union for International Cancer Control TNM staging system. Compared with the eighth edition, the proposed stage groupings incorporating Epstein‐Barr virus DNA provide better hazard consistency, hazard discrimination, outcome prediction, and sample size balance
Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients ...with locoregionally advanced nasopharyngeal carcinoma.
In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival.
We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio HR 4·93, 95% CI 2·99–8·16; p<0·0001), disease-free survival (HR 3·51, 2·43–5·07; p<0·0001), and overall survival (HR 3·22, 2·18–4·76; p<0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19–0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71–1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein–Barr virus DNA status.
The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis.
The National Natural Science Foundation of China, the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the Health & Medical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities.
Abstract
This study uses synchrotron wide‐angle X‐ray diffraction (WAXD) and synchrotron small angle X‐ray scattering (SAXS) to carry out an in situ study of the pre‐oxidation process of ...polyacrylonitrile (PAN) fibers with two different preparation processes. Through analysis of 2D WAXD/SAXS data, this study divides the evolution of PAN fiber's crystal and microporous structures during pre‐oxidation into three and two stages, respectively. The evolution of PAN fiber's crystal structure during pre‐oxidation can be divided into three stages: 1) Initial stage: small‐sized crystals melt, crystal orientation decreases, and no cyclization reactions occur. 2) Intermediate stage: cyclization reactions happen in the amorphous region, leading to increased crystal size, crystal orientation, and crystallinity. 3) Final stage: cyclization reactions occur in the crystal region, resulting in reduced crystal size and orientation. The evolution of microporous structure can be divided into two stages: microporous shrinkage stage and microporous expansion stage. These features are analyzed using 2D WAXD/SAXS techniques. This study provides valuable references and guidance for the industrial production of PAN fibers by exploring the mechanism of the pre‐oxidation process in‐depth.
The antibacterial properties of nanosilver polyethylene packaging play a pivotal role in the fields of food packaging. The difference in the crystalline structure of the materials will affect the ...migration of nanosilver in polyethylene, thereby affecting the antibacterial rate. A series of nanosilver/polyolefin composite films were prepared by melt blending. The investigation included scanning electron microscope‐energy‐dispersed analysis of X‐ray, melt index, thermal properties, small‐angle laser scattering, small‐angle X‐ray scattering, and optical properties, as well as antimicrobial activity against Escherichia coli. The results indicate that the material with a higher melt index has better fluidity and the higher antibacterial rate. Moreover, nanosilver is uniformly dispersed in the substrate. Nanosilver can increase the long period without affecting the crystalline region. For these neat materials, HDPE has the thickest lamellae, which is easier to inhibit the migration of silver, and has the lowest antibacterial rate. Meanwhile, materials with low crystallinity exhibited high antibacterial properties. The crystallinity of the composites was slightly increased by the induction of silver nanoparticles. The optical properties show that nanosilver can reduce the size of spherulites and improve the optical properties of the composites. The research has guiding significance for the commercial production of polyethylene antibacterial packaging materials.
The difference in the crystalline structure of the materials will affect the migration of nanosilver in polyethylene, thereby affecting the antibacterial rate. Nanosilver exists in the amorphous region of materials, and nanosilver is easy to migrate from materials with small lamellar size (such as EVA‐Ag 5ppm) to the surface, and the materials have a higher antibacterial rate.
We aimed to evaluate the value of deep learning on positron emission tomography with computed tomography (PET/CT)-based radiomics for individual induction chemotherapy (IC) in advanced nasopharyngeal ...carcinoma (NPC).
We constructed radiomics signatures and nomogram for predicting disease-free survival (DFS) based on the extracted features from PET and CT images in a training set (
= 470), and then validated it on a test set (
= 237). Harrell's concordance indices (C-index) and time-independent receiver operating characteristic (ROC) analysis were applied to evaluate the discriminatory ability of radiomics nomogram, and compare radiomics signatures with plasma Epstein-Barr virus (EBV) DNA.
A total of 18 features were selected to construct CT-based and PET-based signatures, which were significantly associated with DFS (
< 0.001). Using these signatures, we proposed a radiomics nomogram with a C-index of 0.754 95% confidence interval (95% CI), 0.709-0.800 in the training set and 0.722 (95% CI, 0.652-0.792) in the test set. Consequently, 206 (29.1%) patients were stratified as high-risk group and the other 501 (70.9%) as low-risk group by the radiomics nomogram, and the corresponding 5-year DFS rates were 50.1% and 87.6%, respectively (
< 0.0001). High-risk patients could benefit from IC while the low-risk could not. Moreover, radiomics nomogram performed significantly better than the EBV DNA-based model (C-index: 0.754 vs. 0.675 in the training set and 0.722 vs. 0.671 in the test set) in risk stratification and guiding IC.
Deep learning PET/CT-based radiomics could serve as a reliable and powerful tool for prognosis prediction and may act as a potential indicator for individual IC in advanced NPC.
To compare the results of intensity-modulated radiotherapy (IMRT) with those of two-dimensional conventional radiotherapy (2D-CRT) in the treatment of patients with nasopharyngeal carcinoma (NPC).
A ...retrospective review of data from 1,276 patients with biopsy-proven, nonmetastatic NPC was performed. All patients had undergone magnetic resonance imaging and were staged according to the sixth edition of the American Joint Committee on Cancer staging criteria. Radiotherapy was the primary treatment for all patients.
Of the 1,276 patients, 512 were treated with IMRT and 764 with 2D-CRT. The 5-year actuarial local relapse-free survival (LRFS), the nodal relapse-free survival (NRFS), the distant metastasis-free survival (DMFS), and the disease-free survival (DFS) rates were 92.7%, 97.0%, 84.0%, and 75.9%, respectively, for the IMRT group, and 86.8%, 95.5%, 82.6%, and 71.4%, respectively, for the 2D-CRT group. In stage T1 patients, improvement of LRFS in the IMRT group was even significantly higher than in the 2D-CRT group (100% vs. 94.4%; p = 0.016). A trend of improvement of DFS was observed in the IMRT group compared with the 2D-CRT group but without reaching statistical significance. NRFS and DMFS rates were similar in the two groups.
A greater improvement of treatment results with IMRT than with 2D-CRT was demonstrated primarily by achieving a higher local tumor control rate in NPC patients, especially in the early T stage patients. The goal of better control of both local failure in advanced, nonmetastatic NPC patients and of distant failure should be addressed in future studies.
STUDY DESIGN.A retrospective study.
OBJECTIVE.The purpose of this study was to identify the independent risk factors for postoperative surgical site infection (SSI) after posterior lumbar spinal ...surgery based on the perioperative factors analysis.
SUMMARY OF BACKGROUND DATA.SSI is one of the most common complications after spinal surgery. Previous studies have identified different risk factors for postoperative SSI after lumbar spinal surgery. However, most of the studies were focused on the patient and procedure-related factors. Few studies reported the correlation between laboratory tests and postoperative SSI.
METHODS.A retrospective study was carried out in a single institution. Patients who underwent posterior lumbar spinal surgery between January 2010 and August 2016 were included in this study. All patients’ medical records were reviewed and patients with postoperative SSI were identified. Perioperative variables were included to determine the risk factors for SSI by univariate and multivariate regression analysis.
RESULTS.A total of 2715 patients undergoing posterior lumbar spinal surgery were included in this study. Of these patients, 64 (2.4%) were detected with postoperative SSI, including 46 men and 18 women. Diabetes mellitus (P = 0.026), low preoperative serum level of calcium (P = 0.009), low preoperative and postoperative albumin (P = 0.025 and 0.035), high preoperative serum glucose (P = 0.029), multiple fusion segments (P < 0.001), increased surgical time and estimated blood loss (P = 0.023 and 0.005), decreased postoperative hemoglobin (P = 0.008), and prolonged drainage duration (P = 0.016) were found to be the independent risk factors for SSI. Multilevel fusion and a history of diabetes mellitus were the two strongest risk factors (odds ratio = 2.329 and 2.227) for SSI.
CONCLUSION.Based on a large population analysis, previous reported risk factors for SSI were confirmed in this study while some new independent risk factors were identified significantly associated with SSI following lumbar spinal surgery, including preoperative low serum level of calcium, decreased preoperative and postoperative albumin, and decreased postoperative hemoglobin.Level of Evidence4
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