To construct an immune-related gene prognostic index (IRGPI) for head and neck squamous cell carcinoma (HNSCC) and clarify the molecular and immune characteristics and the benefit of immune ...checkpoint inhibitor (ICI) therapy in IRGPI-defined subgroups of HNSCC.
On the basis of The Cancer Genome Atlas HNSCC immune dataset (
= 546), 22 immune-related hub genes were identified by weighted gene coexpression network analysis. Three genes were identified to construct an IRGPI by using the Cox regression method and validated with the Gene Expression Omnibus (GEO) dataset (
= 270). Afterward, the molecular and immune characteristics and the benefit of ICI therapy in IRGPI-defined subgroups were analyzed.
The IRGPI was constructed on the basis of
,
, and
genes. IRGPI-high patients had a better overall survival than IRGPI-low patients, consistent with the results in the GEO cohort. The comprehensive results showed that a high IRGPI score was correlated with DNA repair-related pathways; low
mutation rate; high infiltration of CD8 T cells, CD4 T cells, and M1 macrophages; active immunity and less aggressive phenotypes; and more benefit from ICI therapy. In contrast, a low IRGPI score was associated with cancer and metastasis-related pathways; high
and
mutation rate; high infiltration of B cells, M0 macrophages, and M2 macrophages; suppressive immunity and more aggressive phenotypes; and less benefit from ICI therapy.
IRGPI is a promising biomarker to distinguish the prognosis, the molecular and immune characteristics, and the immune benefit from ICI therapy in HNSCC.
Long noncoding RNAs (lncRNA) play important roles in the tumorigenesis and progression of cancers. However, the clinical significance of lncRNAs and their regulatory mechanisms in nasopharyngeal ...carcinogenesis (NPC) are largely unknown. Here, based on a microarray analysis, we identified 384 dysregulated lncRNAs, of which,
was one of the most upregulated lncRNAs in NPC.
significantly associated with poor survival in NPC. N(6)-Methyladenosine (m6A) was highly enriched within
and enhanced its RNA stability.
functioned as an oncogenic lncRNA that promoted NPC cell proliferation, migration, invasion, tumor growth, and metastasis. Mechanistically,
functioned as a competing endogenous RNA (ceRNA) for sponging miR-590-3p and miR-1275, leading to the upregulation of their target
(
), and the activation of FAK/PI3K/Akt signaling to promote NPC cell proliferation and invasion. In summary, our study reveals a potential ceRNA regulatory pathway in which
modulates
expression by binding to miR-590-3p and miR-1275, ultimately promoting tumorigenesis and metastasis in NPC. SIGNIFICANCE: These findings demonstrate the clinical significance of the lncRNA
in nasopharyngeal carcinoma (NPC) and the regulatory mechanism involved in NPC development and progression, providing a novel prognostic indicator and promising therapeutic target.
Quality control can decrease variations in the performance of colonoscopists and improve the effectiveness of colonoscopy to prevent colorectal cancers. Unfortunately, routine quality control is ...difficult to carry out because a practical method is lacking. The aim of this study was to develop an automatic quality control system (AQCS) and assess whether it could improve polyp and adenoma detection in clinical practice.
First, we developed AQCS based on deep convolutional neural network models for timing of the withdrawal phase, supervising withdrawal stability, evaluating bowel preparation, and detecting colorectal polyps. Next, consecutive patients were prospectively randomized to undergo routine colonoscopies with or without the assistance of AQCS. The primary outcome of the study was the adenoma detection rate (ADR) in the AQCS and control groups.
A total of 659 patients were enrolled and randomized. A total of 308 and 315 patients were analyzed in the AQCS and control groups, respectively. AQCS significantly increased the ADR (0.289 vs 0.165, P < .001) and the mean number of adenomas per procedure (0.367 vs 0.178, P < .001) compared with the control group. A significant increase was also observed in the polyp detection rate (0.383 vs 0.254, P = .001) and the mean number of polyps detected per procedure (0.575 vs 0.305, P < .001). In addition, the withdrawal time (7.03 minutes vs 5.68 minutes, P < .001) and adequate bowel preparation rate (87.34% vs 80.63%, P = .023) were superior for the AQCS group.
AQCS could effectively improve the performance of colonoscopists during the withdrawal phase and significantly increase polyp and adenoma detection. (Clinical trial registration number: NCT03622281.)
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To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer.
Systematic review and network meta-analysis.
...Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched to include relevant studies published in English between January 2007 and February 2018.
Only head-to-head phase II and III randomised controlled trials comparing any two or three of the following treatments or different doses of the same ICI drug were included: nivolumab, pembrolizumab, ipilimumab, tremelimumab, atezolizumab, conventional therapy (chemotherapy, targeted therapy, and their combinations), two ICI drugs, or one ICI drug with conventional therapy. Eligible studies must have reported site, organ, or system level data on treatment related adverse events. High quality, single arm trials and placebo controlled trials on ICI drugs were selected to establish a validation group.
36 head-to-head phase II and III randomised trials (n=15 370) were included. The general safety of ICI drugs ranked from high to low for all adverse events was as follows: atezolizumab (probability 76%, pooled incidence 66.4%), nivolumab (56%, 71.8%), pembrolizumab (55%, 75.1%), ipilimumab (55%, 86.8%), and tremelimumab (54%, not applicable). The general safety of ICI drugs ranked from high to low for severe or life threatening adverse events was as follows: atezolizumab (49%, 15.1%), nivolumab (46%, 14.1%), pembrolizumab (72%, 19.8%), ipilimumab (51%, 28.6%), and tremelimumab (28%, not applicable). Compared with conventional therapy, treatment-related adverse events for ICI drugs occurred mainly in the skin, endocrine, hepatic, and pulmonary systems. Taking one ICI drug was generally safer than taking two ICI drugs or one ICI drug with conventional therapy. Among the five ICI drugs, atezolizumab had the highest risk of hypothyroidism, nausea, and vomiting. The predominant treatment-related adverse events for pembrolizumab were arthralgia, pneumonitis, and hepatic toxicities. The main treatment-related adverse events for ipilimumab were skin, gastrointestinal, and renal toxicities. Nivolumab had a narrow and mild toxicity spectrum, mainly causing endocrine toxicities. Integrated evidence from the pooled incidences, subgroup, and sensitivity analyses implied that nivolumab is the best option in terms of safety, especially for the treatment of lung cancer.
Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung cancer when taking an integrated approach. The safety ranking of treatments based on ICI drugs is modulated by specific treatment-related adverse events.
PROSPERO CRD42017082553.
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.
Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) ...represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A
dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell-cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A
DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.
Background
The current study was performed to investigate whether circulating cell‐free Epstein‐Barr virus DNA (cfEBV DNA) would be useful for posttreatment surveillance in patients with ...nasopharyngeal carcinoma (NPC).
Methods
The authors identified a total of 1984 nondisseminated NPC patients from an institutional big‐data research platform. Blood samples were collected within 3 months of the completion of radiotherapy and every 3 to 12 months thereafter for cfEBV DNA analysis. Patients were followed until disease recurrence was detected or for a median of 60 months. Diagnostic performance was assessed by calculating the sensitivity, specificity, and accuracy based on the clinical detection of disease recurrence by conventional surveillance modalities (imaging scans and pathological examination).
Results
During follow‐up, a total of 767 patients (38.7%) had detectable cfEBV DNA. The recurrence rate among these patients was 63.8% (489 of 767 patients), which was significantly higher than that in patients with undetectable cfEBV DNA (8.6%; 105 of 1217 patients). cfEBV DNA sensitivity, specificity, and accuracy were 68.8%, 80.0%, and 78.2%, respectively, for local recurrence; 80.2%, 80.0%, and 85.9%, respectively, for regional recurrence; and 91.1%, 80.0%, and 92.8%, respectively, for distant metastasis. cfEBV DNA was found to have higher sensitivity for the detection of extrapulmonary metastases (94.9%‐96.5%) compared with pulmonary metastases (78.4%). It is interesting to note that among the patients with disease recurrence with detectable cfEBV DNA, positive cfEBV DNA results preceded radiological and/or clinical evidence of disease recurrence by a median of 2.3 months (interquartile range, 0.1‐9.5 months). In addition, of the 278 cfEBV DNA‐positive patients who did not develop disease recurrence, 227 (81.7%) had transiently positive cfEBV DNA that fell to undetectable levels during long‐term monitoring.
Conclusions
Plasma cfEBV DNA in patients with NPC appears to be an early sign of tumor recurrence, especially extrapulmonary metastases.
Circulating cell‐free Epstein‐Barr virus (EBV) DNA levels in the plasma can be useful for detecting tumor recurrence early after treatment in patients with nasopharyngeal carcinoma, particularly those with extrapulmonary metastases. Positive circulating cell‐free EBV DNA can be detected at a median of 2.3 months before radiological or clinical evidence of disease recurrence is noted.
To clarify the optimal cumulative cisplatin dose (CCD) in locoregionally‐advanced nasopharyngel carcinoma (NPC) patients receiving induction chemotherapy (IC) plus concurrent chemoradiotherapy ...(CCRT). Using the NPC‐specific database from the established big‐data intelligence platform at Sun Yat‐Sen University Cancer Center, 583 non‐disseminated, locoregionally‐advanced NPC patients receiving IC plus CCRT were enrolled. Propensity score matching (PSM) analysis was conducted to control for confounding factors. The median CCD was 160 mg/m2 after IC (range, 40‐300 mg/m2); only 74 patients (12.7%) achieved CCD >200 mg/m2. Patients receiving >200 mg/m2 CCD did not show significantly improved 5‐year overall survival (OS) (HR = 1.19; 95% confidence intervals CI 0.69‐2.06, P = .53) and progression‐free survival (PFS) (HR = 1.03; 95% CI: 0.63‐1.68, P = .92) compared with patients receiving <200 mg/m2 CCD. Further investigations of the potential of median CCD (160 mg/m2) to yield survival benefits revealed that there were no significant differences in survival endpoints between patients receiving CCD >160 mg/m2 and CCD < 160 mg/m2 in both the original and PSM cohorts. In addition, subgroup analysis indicated a favorable PFS, but not OS, with higher cisplatin administration in patients with pretreatment Epstein–Barr virus deoxyribonucleic acid (EBV DNA) <1000 copies/mL (HR = 0.26, 95% CI: 0.07‐0.93, P = .03) and receiving <3 IC cycles (HR = 0.59, 95% CI 0.33‐1.07, P = .08). Our analysis of real world data provided references for the optimal CCD in locoregionally‐advanced NPC receiving additional IC. The causal relationship between 200 mg/m2 CCD and improved survival was not defined; 160 mg/m2 CCD might be enough. However, for patients with EBV DNA <1000 copy/mL and receiving <3 IC cycles, a higher dose might be necessary.
Our analysis of real world data provided references for the optimal CCD in locoregionally‐advanced NPC receiving IC plus CCRT. The causal relationship between 200 mg/m2 CCD and improved survival was not defined; 160 mg/m2 CCD might be enough. However, for patients with EBV DNA < 1000 copy/mL, and receiving<3 IC cycles, higher dose might be necessary.
As newly emerged crystalline porous materials, covalent organic frameworks (COFs) possess fascinating structures and some specific features such as modularity, crystallinity, porosity, stability, ...versatility, and biocompatibility. Besides adsorption/separation, sensing, catalysis, and energy applications, COFs have recently shown a promise in biomedical applications. This contribution provides an overview of the recent developments of COF‐based medicines in cancer therapeutics, including drug delivery, photodynamic therapy (PDT), photothermal therapy (PTT), and combined therapy. Furthermore, the major challenges and developing trends in this field are also discussed. These recent developments are summarized and discussed to help encourage further contributions in this emerging and promising field.
Magic bullet: In this minireview, recent advances in the field of covalent organic frameworks (COFs) for cancer therapeutic applications are highlighted, including those for drug delivery, phototherapy, and combined therapy.
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