Ovarian cancer is the leading cause of death in gynecologic malignancies. Profiling of endogenous metabolites has potential to identify changes caused by cancer and provide inspiring insights into cancer metabolism. To systematically investigate ovarian cancer metabolism, we performed metabolic profiling of 448 plasma samples related to epithelial ovarian cancer (EOC) based on ultra-performance liquid chromatography mass spectrometry in both positive and negative modes. These unbiased metabolomic profiles could well distinguish EOC from benign ovarian tumor (BOT) and uterine fibroid (UF). Fifty-three metabolites were identified as specific biomarkers for EOC, and this is the first report of piperine, 3-indolepropionic acid, 5-hydroxyindoleacetaldehyde and hydroxyphenyllactate as metabolic biomarkers of EOC. The AUC values of these metabolites for discriminating EOC from BOT/UF and early-stage EOC from BOT/UF were 0.9100/0.9428 and 0.8385/0.8624, respectively. Meanwhile, our metabolites were able to distinguish early-stage EOC from late-stage EOC with an AUC of 0.8801. Importantly, analysis of dysregulated metabolic pathways extends our current understanding of EOC metabolism. Metabolic pathways in EOC patients are mainly characterized by abnormal phospholipid metabolism, altered L-tryptophan catabolism, aggressive fatty acid b-oxidation and aberrant metabolism of piperidine derivatives. Together, these metabolic pathways provide a foundation to support cancer development and progression. In conclusion, our large-scale plasma metabolomics study yielded fundamental insights into dysregulated metabolism in ovarian cancer, which could facilitate clinical diagnosis, therapy, prognosis and shed new lights on ovarian cancer pathogenesis.Epithelial ovarian cancer (EOC) remains one of the most common gynecologic malignancies, and has an alarming global fatality rate. Worldwide, about 204,000 new cases of ovarian cancer are diagnosed and 125,000 women succumb to ovarian cancer each year.1 The majority of patients tend to present with advanced disease, with 5-year survival rates below 20%. 2 The 5-year survival rate for localized ovarian cancer is greater than 90%, but only 15% of all patients are diagnosed when the disease is still localized.3 These unfavorable statistics highlight a lack of effective detection methods and essentially a poor understanding of the molecular pathogenesis of ovarian cancer. Altered metabolism is well-established as a hallmark of tumors, and could be used to distinguish cancer patients from their counterparts and potentially clarify disease pathogenesis. 4 Many studies have shown increased rates of glycolysis, glutaminolysis and lipid synthesis in cancers, suggesting that metabolic alterations provide a foundation to fuel tumor

The language history questionnaire (LHQ) is an important tool for assessing the linguistic background and language proficiency of multilinguals or second language learners. Previously we developed a generic LHQ based on the most commonly asked questions in published studies (Li, Sepanski & Zhao, 2006) and provided a web-based interface (LHQ 2.0) that has flexibility in functionality, accuracy in data recording, and privacy for users and data (Li, Zhang, Tsai & Puls, 2014). LHQ3 (version 3) introduces new functions, developed in response to many comments/requests from users. One important improvement is the addition of an automatic scoring system, in that the new interface automatically calculates aggregated scores for language proficiency, language dominance, and language immersion levels. Finally, LHQ3 allows researchers to assign different weights to the modules when calculating the aggregated scores, addressing the issue of different focuses that different researchers put on multilingual speakers’ language usage and background.

E2Fs are a family of pivotal transcription factors. Accumulative evidence indicates that aberrant expression or activation of E2Fs is a common phenomenon in malignances, and significant associations have been noted between E2Fs and tumorigenesis or progression in a wide range of cancers. However, the expression patterns and exact roles of each E2F contributing to tumorigenesis and progression of ovarian cancer (OC) have not yet been elucidated. In this study, we investigated the distinct expression and prognostic value of E2Fs in patients with OC by analyzing a series of databases, including ONCOMINE, GEPIA, cBioPortal, Metascape, and Kaplan–Meier plotter. The mRNA expression levels of E2F1/3/5/8 were found to be significantly upregulated in patients with OC and were obviously associated with tumor stage for OC. Aberrant expression of E2F2/5/7/8 was found to be associated with the clinical outcomes of patients with OC. These results suggest that E2F2/5/8 might serve as potential prognostic biomarkers and targets for OC. However, future studies are required to validate our findings and promote the clinical utility of E2Fs in OC.

BackgroundIn locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone.MethodsAll patients, including retrospective training (n = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959, n = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts.ResultsThree imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25–0.74, p = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups (p = 0.063), with a significant treatment interaction (pinteraction <  0.001). This trend was also found in the validation cohort with high (n = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06–0.51, p <  0.001) and low ICTOS (n = 175, p = 0.31), with a significant treatment interaction (pinteraction = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors.ConclusionAn imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment.Trial registrationClinicalTrials.gov, NCT01245959. Registered 23 November 2010.

The prognostic value of the tumour response to induction chemotherapy (IC) for long-term survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma (NPC) remains unknown. We retrospectively reviewed 1811 consecutive patients with newly diagnosed NPC treated using IMRT, and 399 eligible patients with pre- and post-induction chemotherapy magnetic resonance images were recruited. The clinicopathological features of patients with different tumour responses were compared using the Chi-square test or Fisher’s exact test. Prognostic value was assessed using a multivariate Cox proportional hazards model. After IC, 101/399 (25.3%) patients had a complete tumour response overall (CR), 262 (65.7%) had a partial response (PR) and 36 (9.0%) had stable disease (SD). The 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates for CR vs. PR vs. SD were 90.0% vs. 79.0% vs. 58.2% (CR vs. PR: P1 = 0.007; CR vs. SD: P2 < 0.001; PR vs. SD: P3 = 0.004), 95.7% vs. 88.7% vs. 70.2% (P1 = 0.017, P2 < 0.001, P3 = 0.005), 92.0% vs. 87.4% vs. 74.3% (P1 = 0.162, P2 = 0.005, P3 = 0.029) and 95.9% vs. 88.8% vs. 81.8% (P1 = 0.024, P2 = 0.006, P3 = 0.268), respectively. Multivariate analysis identified that the tumour response to IC was an independent prognostic factor for DFS, OS and LRRFS.

Conclusions:The dynamic change of CEA, CA125, CYFRA21-1, and SCC-Ag from baseline have prognostic value for late-stage NSCLC patients treated with PD-1/PD-L1 inhibitors. Decrease of associated biomarkers serum levels were associated with favorable clinical outcomes.

Purpose Nicotinamide n‐methyltransferase (NNMT) has good biochemical activity and epigenetic regulation, and has been reported as a major metabolic regulator of cancer. The goal of this study was to investigate the significance of stromal NNMT expression in colorectal cancer (CRC). Patients and methods Stromal expression of NNMT in primary CRC, metastasis CRC, and their non‐cancerous tissues from 1088 CRC patients was examined by immunohistochemistry. The associations between stromal NNMT expression and survival outcomes in 967 patients with stage I‐III CRC were further evaluated with Kaplan‐Meier curve and Cox model analyses. Results NNMT expression was mainly sourced from stromal compartments and also elevated in CRC. Patients with high stromal NNMT (IHC‐score ≥ 106) have a worse survival than those patients with low stromal NNMT. In multiple Cox analyses, high expression of stromal NNMT remained as an independent risk factor in CRC for disease‐free survival with a hazard ratio (HR) of 1.415 (95% confidence interval [CI], 1.015‐1.972) and disease‐specific survival with a HR of 5.004 (95% CI, 2.301‐10.883). In addition, high stromal NNMT expression in CRC also indicates the poor survival outcomes in patients with early stage CRC (stage I and II) and in patients who undergo chemotherapy. Conclusion NNMT is mainly located in CRC stromal compartment. High stromal NNMT expression predicts an unfavorable postoperative prognosis.

Preoperative serum albumin may be related to GC patient survival and may hold promise as a prognostic predictor for such survival.