Despite evidence suggesting the utility of Epstein‐Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high‐risk regions, no validated NPC risk ...prediction model exists. We aimed to validate an EBV‐based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver‐operator‐characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross‐validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV‐based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93‐0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0‐92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9‐3.0%) to 12.5% (9.9‐15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255‐290) to 50 (41‐59). Combining the score with other risk factors (sex, first‐degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5‐year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high‐risk population. Adding nonviral risk factors did not improve NPC prediction.
What's new?
Evidence suggests that markers of Epstein‐Barr virus (EBV) infection are useful in screening for nasopharyngeal carcinoma (NPC). Few prospective studies, however, have validated the performance of EBV‐based risk scores for NPC. In this prospective validation study with data for more than 51 000 participants, EBV‐based risk score based on the combination of IgA antibodies against viral capsid antigen and EBV nuclear antigen 1 was found to be highly discriminating for NPC over follow‐up periods lasting five years. The findings indicate that EBV‐based scores could be valuable risk‐prediction tools for early NPC diagnosis, leading to improved clinical outcomes.
Metabolic reprogramming plays important roles in development and progression of nasopharyngeal carcinoma (NPC), but the underlying mechanism has not been completely defined. In this work, we found ...INSL5 was elevated in NPC tumor tissue and the plasma of NPC patients. Plasma INSL5 could serve as a novel diagnostic marker for NPC, especially for serum VCA‐IgA‐negative patients. Moreover, higher plasma INSL5 level was associated with poor disease outcome. Functionally, INSL5 overexpression increased, whereas knockdown of its receptor GPCR142 or inhibition of INSL5 reduced cell proliferation, colony formation, and cell invasion in vitro and tumorigenicity in vivo. Mechanistically, INSL5 enhanced phosphorylation and nuclear translocation of STAT5 and promoted glycolytic gene expression, leading to induced glycolysis in cancer cells. Pharmaceutical inhibition of glycolysis by 2‐DG or blockade of INSL5 by a neutralizing antibody reversed INSL5‐induced proliferation and invasion, indicating that INSL5 can be a potential therapeutic target in NPC. In conclusion, INSL5 enhances NPC progression by regulating cancer cell metabolic reprogramming and is a potential diagnostic and prognostic marker as well as a therapeutic target for NPC.
Synopsis
This study reveals that INSL5 promotes tumor progression by regulating cancer cell metabolic reprogramming. INSL5 is a potential diagnostic and prognostic marker as well as a therapeutic target for nasopharyngeal carcinoma (NPC).
INSL5 expression levels are elevated in NPC tumor tissue and in the plasma of NPC patients.
INSL5 plasma levels are associated with NPC patient outcome.
INSL5 promotes tumor progression through an autocrine mechanism involving binding to its receptor GPCR142.
INSL5 activates JAK1‐STAT5 signal pathway and promotes glycolytic gene expression, which in turn induces metabolic reprogramming in cancer cells.
INSL5‐GPCR142 axis can be a potential therapeutic target for NPC.
This study reveals that INSL5 promotes tumor progression by regulating cancer cell metabolic reprogramming. INSL5 is a potential diagnostic and prognostic marker as well as a therapeutic target for nasopharyngeal carcinoma (NPC).
A shaking table test of a steel frame with autoclaved lightweight concrete (ALC) external wall panels is described in this paper. The specimen is a two-story full-scale model filled with external ...vertical wall panels, external horizontal wall panels and internal vertical wall panels. The input wave of the shaking table was generated by the El-Centro 1940 earthquake spectrum. Based on the experimental results, the seismic behavior of ALC external walls and joints was analyzed, such as the failure modes of ALC external walls and joints and the effects of external walls on the dynamic response of steel frame. The test results show that there is no great crack or damage on the wall panels at the tenth seismic intensity because of the enough intensity. The comparison between the steel frame models with and without wall panels indicates that the contribution of external wall panels to the steel frame stiffness can reach up to 25% and the damping ratio can exceed 7%. The analysis results also show that the joints are stable enough to resist the seismic loads and can provide enough flexible deformation so that the wall panels can stand large structure deformation. The screws on band iron of openings are very easy to loosen. Therefore, the joints between the band iron and wall panels should be reinforced.
► Seismic behavior of autoclaved lightweight concrete (ALC) wall panels is discussed. ► Effect of ALC external wall panels on the steel frame dynamic behavior is analyzed. ► Properties of joints between walls and steel frame are discussed. ► Properties of different wall panel layout are compared and several suggestions for design are presented.
To investigate the relationship between the expressions of p53 pathway genes and EZH2 in nasopharyngeal carcinoma (NPC).
The expression levels of p53, mdm2, p63 and EZH2 proteins were detected by ...immunohistochemistry in 47 cases of undifferentiated NPC and 12 cases of chronic nasopharyngitis, and their correlation to the clinical parameters and prognosis were analyzed.
The protein expressions of p53, mdm2, p63 and EZH2 in NPC were 31.9%, 85.1%, and 95.7%, respectively. mdm2 and EZH2 was not correlated to p53 protein expression (P>0.05); positive correlations was found between EZH2 and p63 expressions and between p53 and p63. The high expression of EZH2 and p63 proteins was correlated to advanced T stage and clinical stage of NPC (P<0.05). The five-year disease-free survival rate in patients with high EZH2 protein expression was significantly lower than that in patients with low EZH2 expression.
mdm2 does not show an obvious correlation to p53 protein inactivation in NPC. p63 protein overexpression may be asso
A nasopharyngeal carcinoma (NPC) mass screening trial using a combination of immunoglobulin A antibodies to Epstein-Barr virus capsid antigen and nuclear antigen-1 by enzyme-linked immunosorbent ...assay in addition to indirect mirror examination in the nasopharynx and/or lymphatic palpation (IMLP) was conducted in southern China. Cantonese aged 30-59 years residing in 2 cities randomly selected by cluster sampling, Sihui and Zhongshan, were invited to participate in this screening from May 2008 through May 2010. Participants were offered fiberoptic endoscopy examination and/or pathologic biopsy if their serologic tests reached our predefined level of high risk or if results from the physical examination indicated possible cancer (i.e., were IMLP positive). A total of 28,688 individuals were voluntarily screened in the initial round. The overall NPC detection rate was 0.14% (41/28,688) with an early diagnosis rate of 68.3% (28/41) during the first year of follow-up. Thirty-eight of 41 cases (92.7%) were detected among the high-risk group, and 7 of 41 cases (17.1%) were detected among the IMLP-positive group. The 2 Epstein-Barr virus serologic tests by enzyme-linked immunosorbent assay could be a feasible alternative for NPC screening in endemic areas. Further follow-up is needed to examine whether screening has an effect on decreasing mortality from NPC in these areas.
Liver cancer is a common malignant tumor in China and a major health concern. We aimed to estimate the liver cancer incidence and mortality in China in 2010 using liver cancer data from some Chinese ...cancer registries and provide reference for liver cancer prevention and treatment. We collected and evaluated the incidence and mortality data of liver cancer in 2010 from 145 cancer registries, which were included in the 2013 Chinese Cancer Registry Annual Report, calculated crude, standardized, and truncated incidences and mortalities, and estimated new liver cancer cases and deaths from liver cancer throughout China and in different regions in 2010 from Chinese practical population. The estimates of new liver cancer cases and deaths were 358,840 and 312,432, respectively, in China in 2010. The crude incidence, age-standardized rate by Chinese standard population （ASR China）, and age-standardized rate by world standard population （ASR world） were 27.29/100,000, 21.35/100,000, and 20.87/100,000, respectively; the crude, ASR China, and ASR world mortalities were 23.76/100,000, 18.43/100,000, and 18.04/100,000, respectively. The incidence and mortality were the highest in western regions, higher in rural areas than in urban areas, and higher in males than in females. The age-specific incidence and mortality of liver cancer showed a rapid increase from age 30 and peaked at age 80-84 or 85＋. Our results indicated that the 2010 incidence and mortality of liver cancer in China, especially in undeveloped rural areas and western regions, were among high levels worldwide. The strategy for liver cancer prevention and treatment should be strengthened.
Metabolic reprogramming plays important roles in development and progression of nasopharyngeal carcinoma (NPC), but the underlying mechanism has not been completely defined. In this work, we found ...INSL5 was elevated in NPC tumor tissue and the plasma of NPC patients. Plasma INSL5 could serve as a novel diagnostic marker for NPC, especially for serum VCA‐IgA‐negative patients. Moreover, higher plasma INSL5 level was associated with poor disease outcome. Functionally, INSL5 overexpression increased, whereas knockdown of its receptor GPCR142 or inhibition of INSL5 reduced cell proliferation, colony formation, and cell invasion in vitro and tumorigenicity in vivo. Mechanistically, INSL5 enhanced phosphorylation and nuclear translocation of STAT5 and promoted glycolytic gene expression, leading to induced glycolysis in cancer cells. Pharmaceutical inhibition of glycolysis by 2‐DG or blockade of INSL5 by a neutralizing antibody reversed INSL5‐induced proliferation and invasion, indicating that INSL5 can be a potential therapeutic target in NPC. In conclusion, INSL5 enhances NPC progression by regulating cancer cell metabolic reprogramming and is a potential diagnostic and prognostic marker as well as a therapeutic target for NPC.
Research papers and data concerning NPC epidemiology in China available worldwide were reviewed. It was found that although the results of three national all death-causes sampling surveys in China ...showed mortality rates in most sampling areas and all as overall to be declining continuously and remarkably, figures for 1987-2000 in some selected areas of China released by the World Health Organization were relatively stable, and the NPC incidence and mortality rates reported by Zhongshan and Sihui cities of Guangdong Province in China had shown ascending or stable trends, respectively. Differences with regard to change in NPC incidence and mortality rates over time may be caused by variation in the data quality from divergent sources, but the exact reasons clearly warrant further analysis.
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