[Prognostic value of a predictive model comprising preoperative inflammatory response and nutritional indexes in patients with gastric cancer].

Objective: To investigate the prognostic value of preoperative inflammatory and nutritional condition detection in the postoperative survival, and establish a prognostic model for predicting the survival of patients with gastric cancer. Methods: The clinicopathological data of 1123 patients with gastric cancer who had undergone radical gastrectomy in Tianjin Medical University Cancer Institute & Hospital from January 2005 to December 2014 were retrospectively analyzed. Patients with history of other malignancy, with history of gastrectomy, who had received preoperative treatment, who died during the initial hospital stay or first postoperative month, and missing clinical and pathological information were excluded. Cox univariate and multivariate analyses were used to identify independent clinicopathological factors associated with the survival of these gastric cancer patients. Cox univariate analysis was used to identify preoperative inflammatory and nutritional indexes related to the survival of patients with gastric cancer after radical gastrectomy. Moreover, the Cox proportional regression model for multivariate survival analysis (forward stepwise regression method based on maximum likelihood estimation) was used. The independent clinicopathological factors that affect survival were incorporated into the following three new prognostic models: (1) an inflammatory model: significant preoperative inflammatory indexes identified through clinical and univariate analysis; (2) a nutritional model: significant preoperative nutritional indexes identified through clinical and univariate analysis; and (3) combined inflammatory/nutritional model: significant preoperative inflammatory and nutritional indexes identified through clinical and univariate analysis. A model that comprised only pT and pN stages in tumor TNM staging was used as a control model. The integrated area under the receiver operating characteristic curve (iAUC) and C-index were used to evaluate the discrimination of the model. Model fitting was evaluated by Akaike information criterion analysis. Calibration curves were used to assess agreement between the predicted probabilities and actual probabilities at 3-year or 5-year overall survival (OS). Results: The study cohort comprised 1 123 patients with gastric cancer. The mean age was 58.9±11.6 years, and 783 were males. According to univariate analysis, age, surgical procedure, extent of lymph node dissection, tumor location, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and nerve invasion were associated with 5-year OS after radical gastrectomy for gastric cancer (all P<0.050). Multivariate analysis further identified age (HR: 1.18, 95%CI: 1.03-1.36, P=0.019), maximum tumor size (HR: 1.19, 95%CI: 1.03-1.38, P=0.022), number of examined lymph nodes (HR: 0.79, 95%CI: 0.68-0.92, P=0.003), pT stage (HR: 1.40, 95%CI: 1.26-1.55, P<0.001) and pN stage (HR: 1.28, 95%CI: 1.21-1.35, P<0.001) as independent prognostic factors for OS of gastric cancer patients. Additionally, according to univariate survival analysis, the preoperative inflammatory markers of neutrophil count, percentage of neutrophils, neutrophil/lymphocyte ratio, platelet/neutrophil ratio and preoperative nutritional indicators of serum albumin and body mass index were potential prognostic factors for gastric cancer (all P<0.05). On the basis of the above results, three models for prediction of prognosis were constructed. Variables included in the three models are as follows. (1) Inflammatory model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, and neutrophil-lymphocyte ratio; (2) nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, and serum albumin; and (3) combined inflammatory/nutritional model: age, maximum tumor size, number of examined lymph nodes, pT stage, pN stage, percentage of neutrophils, neutrophil-lymphocyte ratio, and serum albumin. We found that the predictive accuracy of the combined inflammatory/nutritional model, which incorporates both inflammatory indicators and nutrition indicators (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.698),was superior to that of the inflammation model (iAUC: 0.662, 95% CI: 0.673-0.706;C-index: 0.675), nutritional model (iAUC: 0.666, 95% CI: 0.642-0.698, C-index: 0.672), and TNM staging control model (iAUC: 0.676, 95% CI: 0.650-0.719, C-index: 0.658). Furthermore, the combined inflammatory/nutritional model had better fitting performance (AIC: 10 762) than the inflammatory model (AIC: 10 834), nutritional model (AIC: 10 810), and TNM staging control model (AIC: 10 974). Conclusions: Preoperative percentage of neutrophils, NLR, and BMI have predictive value for the prognosis of gastric cancer patients. The inflammatory / nutritional model can be used to predict the survival and prognosis of gastric cancer patients on an individualized basis.

ETV4 promotes the progression of gastric cancer through regulating KDM5D.

OBJECTIVE: This study was aimed to investigate the expression characteristics of ETS variant 4 (ETV4) in gastric cancer (GCa), and to further explore whether it promotes the development of GCa by regulating KDM5D. PATIENTS AND METHODS: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of ETV4 in 35 pairs of tumor tissue and paracancerous tissue specimens collected from GCa patients, and the interplay between ETV4 expression and clinical indexes, as well as the prognosis of GCa patients, were analyzed. Meanwhile, the expression of ETV4 in GCa cell lines was verified using qRT-PCR assay. Furthermore, ETV4 knockdown model was constructed using lentivirus in GCa cell lines including AGS and BGC-823, and then, the transwell invasion and cell wound healing assays were applied to analyze the effect of ETV4 on the biological function of GCa cells. In addition, an in-depth study of the relationship between ETV4 and KDM5D was conducted. RESULTS: The results of qRT-PCR showed that the expression level of ETV4 in GCa tissue samples was remarkably higher than that in adjacent tissues, and the difference was statistically significant. Compared with patients with low expression of ETV4, the patients with high ETV4 expression had a higher occurrence rate of lymph node or distant metastasis and a lower overall survival rate. Similarly, the metastasis ability of GCa cells in the ETV4 expression knockdown group (sh-ETV4) was remarkably decreased when compared with the sh-NC group. In addition, qRT-PCR results indicated that the protein expression of KDM5D was significantly increased after the knockdown of ETV4. Therefore, it was demonstrated that ETV4 might be able to regulate the malignant progression of GCa via modulating KDM5D expression. Finally, the results of the cell reverse experiment confirmed that the silence of ETV4 could reverse the malignant progression of GCa induced by the downregulation of KDM5D. CONCLUSIONS: ETV4 expression was found remarkably elevated in GCa tissues and was significantly associated with the occurrence of lymph node or distant metastasis and poor prognosis. In addition, ETV4 might promote GCa cell metastasis by modulating KDM5D.

Resonance Raman detection of a carotenoid in the lens of the deep-sea hatchetfish.

A laser scanning micro-probe has been used to elicit resonance Raman signals from frozen sections of the lens of the deep-sea hatchetfish, Argyropelecus affinis. The signals demonstrate with certainty the presence of a carotenoid and its distribution in the lens. The carotenoid exhibits characteristic resonance Raman vibrational modes at 1551 cm-1 (C = C stretch, v1), 1147 cm-1 (C-C stretch with C-H bend, v2), 2285 cm-1 (2v2) and 2681 cm-1 (v1 + v2), upon excitation at 441.6 nm. Unlike glycogen in the nucleus of dove lens, the carotenoid in the lens of A. affinis occurs at a higher concentration in the cortex, although its presence in the nucleus is established. A study of lenses of varying age showed that carotenoid incorporation is accelerated as the fish grows older and hence its concentration is highest in the cortex. Because of the extremely low concentration of the carotenoid in the nucleus, it was detectable only by the very sensitive resonance Raman technique.

Galactose-induced cataract in rat: Raman detection of sulfhydryl decrease and water increase along an equatorial diameter.

Raman spectroscopy shows that maturation of galactose cataract greatly increases the water signal (at 3417 cm-1) which is correlated with the inbibition of water in the lens. The maximum water: protein ratio (expressed as Raman intensity ratio I3417:I2936) occurs at the peripheral cortex (i.e. approximately 4.7), which is much higher than the ratios found in Emory cataract (approximately 0.3) and in cac-strain mouse cataract (approximately 0.5). It is demonstrated that Raman measurement of the intensity ratio I3417:I2936 is a more sensitive way to reflect increase of water in cataract, compared to water concentration (percentage of wet weight of the lens). The small decrease in the sulfhydryl profile along an equatorial diameter is attributed to the concentration decrease in glutathione. There is no spectroscopic evidence for extensive disulfide bond formation associated with galactosemic cataractogenesis in rat. There is an increase in the tyrosine I832:I858 ratio (normal 1.74; cataract 3.43), indicating a strengthening of the phenolic hydrogen bond, a change which has been found in Raman spectra of all cataracts studied. A comparison of the Raman spectra of normal lenses and mature cataracts reveals no change in conformation of the protein backbone.

Automated laser-scanning-microbeam fluorescence/Raman image analysis of human lens with multichannel detection: evidence for metabolic production of a green fluorophor.

A laser-microprobe fluorescence/Raman spectrometer with a 700-channel detector has been constructed and applied to the collection of data on the distribution of a green fluorophor throughout the exposed area of a human lens sectioned along the visual axis. The area (approximately 6.5 X 9.5 mm) covering the lens section was scanned automatically by the microprobe programmed to measure the fluorescence intensity at 1200 data points. The spectrometer output was accumulated in a microcomputer and displayed as a three-dimensional perspective view showing the fluorescence intensity at each point on the grid. The method permits the precise and detailed mapping at high resolution of the spatial distribution of a fluorophor or Raman-emissive constituent in a plane of the frozen lens to give results not obtainable by any other feasible procedure. The green fluorophor (441.6 nm, excitation wavelength; 520 nm, peak emission wavelength) has a distribution indicating a metabolic rather than a photochemical mode of production. Moreover, the lower level of fluorophor in the anterior segment suggests the existence of mechanisms in the anterior cortex (including the epithelium) that reduce significantly the accumulation of fluorophor. Such distribution studies are invaluable in clarifying metabolic interrelationships among the different zones of the lens, including especially photochemical reactions postulated to involve the effect of daylight on the lens in human subjects.