ABSTRACT
Objective:To explore the correlation of serum cystatin C (CysC), serum and glucocorticoid-regulated kinase 1 (SGK1) and homocysteine ??(Hcy) with postoperative lymph node metastasis in patients with lung cancer and their predictive values.Methods:One hundred and thirty-one patients with stage Ⅰ-Ⅲ A non-small cell lung cancer (NSCLC) who underwent tumor resection and systematic lymph node dissection in Meishan Hospital of Traditional Chinese Medicine from November 2016 to June 2018 were prospectively selected. Patients received a 3-year follow-up after surgery, and were classified into metastasis group (42 cases) and non-metastasis group (89 cases) according to the presence or absence of lymph node metastasis during the follow-up period. Serum CysC, SGK1 and Hcy levels were detected at the 1st day after surgery, and the levels of the three indicators were compared among patients with different TNM stages, differentiation degrees and histological types. Meantime, the clinicopathological characteristics and levels of the three indicators were also compared between metastasis group and non-metastasis group. Spearman analysis was conducted to discuss the correlation between the three indicators and clinicopathological characteristics of patients. Multivariate logistic regression analysis was performed to screen the factors affecting postoperative lymph node metastasis (the median levels of CysC, SGK1 and Hcy were used as the cut-off values, > the median level was a high level). Taking the pathological examination results as the gold standard, receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of level of the three indicators alone or in combination for postoperative lymph node metastasis. Results:The serum levels of CysC, SGK1 and Hcy in patients with TNM stage Ⅲ A were higher than those in patients with stageⅠ-Ⅱ; the serum levels of CysC, SGK1 and Hcy in patients with poorly differentiated tumors were higher than those in patients with medium and well-differentiated tumors; the serum levels of CysC, SGK1 and Hcy in patients with non-squamous cell carcinoma were higher than those in patients with squamous cell carcinoma; the differences were statistically significant (all P < 0.05). Spearman correlation analysis showed that serum CysC, SGK1 and Hcy levels were correlated with TNM stage ( r values were 0.454, 0.672 and 0.645), differentiation degree ( r values were -0.399, -0.403 and -0.451), histological type ( r values were 0.528, 0.760 and 0.611) (all P < 0.001). Compared with non-metastasis group, an elevation was found in serum levels of CysC, SGK1 and Hcy in metastasis group [(1.37±0.30) mg/L vs. (1.16±0.25) mg/L, (53±4) pg/ml vs. (41±3) pg/ml, (18.3±2.3) mol/L vs. (15.4±1.8) mol/L] (all P < 0.001). Multivariate logistic regression analysis showed that TNM stage Ⅲ A ( OR = 2.944, 95% CI 1.556-6.847, P = 0.004) and high level of CysC (> 1.23 mg/L, OR = 2.431, 95% CI 1.402-5.226, P = 0.008), high level of SGK1 (>50 pg/ml, OR = 4.010, 95% CI 1.815-11.748, P = 0.004), high level of Hcy (> 16.8 μmol/L, OR = 3.742, 95% CI 1.747-9.142, P = 0.001) were independent risk factors for postoperative lymph node metastasis. ROC curve analysis showed that for predicting postoperative lymph node metastasis, the area under the curve (AUC) of serum CysC, SGK1 or Hcy level alone was 0.769, 0.808 and 0.816, the AUC of CysC+Hcy, CysC+SGK1 and Hcy+SGK1 was 0.889, 0.890 and 0.910, and the AUC of the three indicators was 0.936. Conclusions:Levels of serum CysC, SGK1 and Hcy in NSCLC patients with postoperative metastasis are higher than those in patients without metastasis, and the levels of the three are positively correlated with the TNM stage and histological type, and negatively correlated with the differentiation degree. The combined detection of the three has good predictive value for postoperative lymph node metastases in NSCLC patients.
ABSTRACT
Objective To investingate the effect of SGK1 expression level on the prognosis of patients with NSCLC,and provide new biological predictors for the prognosis assessment of patients with NSCLS.Methods One hundred and twenty patients with NSCLC received radical resection in Hanzhong 3201 hospital from Jan 2011 to Dec 2013 were selected.There were 75 males and 45 females,age (63.15 ± 16.44) years,age range 45-80 years.According to the results of immunohistochemical staining,the SGK1 cut-off value determined by the integral was determined,and NSCLC patients were divided into SGK1 high expression group (n =70) and SGK1 low expression group(n =50).The relationship between the expression of SGK1 and clinicopathological features (age,sex,smoking history,alcoholism history,BMI,tissue type,tumor diameter,T stage,N stage,TNM stage,differentiation degree) in NSCLC were analyzed,and the overall survival rate in NSCLC were also analyzed.Followup was carried out by telephone or patient admission.The follow-up period was up to June 1,2018.Chest X-ray and ultrasonography were reviewed every 3 to 6 months after operation,and enhanced CT or MRI were performed if the results were abnormal.The measurement data conforming to normal distribution were expressed by t test and showed by (Mean ± SD);the counting data were tested by x2 test;the 5-year overall survival rate was used as the endpoint event for univariate analysis,and the significant variables for univariate analysis were analyzed by COX risk ratio model for multivariate analysis.The cumulative survival curve was drawn by Kaplan-Meier method,and the difference was tested by Log-rank method.Results The expression level of SGK1 in tissues was not related to age,sex,smoking history,alcoholism,BMI,tissue type and tumor diameter (P ＞ 0.05),but it was related to T stage,N stage,TNM stage and differentiation degree (P ＜ 0.05).The univariate and multivariate COX risk ratio model showed that TNM stage and SGK1 expression were independent factors affecting the 5-year overall survival rate of NSCLC patients (P ＜ 0.05).The results of Kaplan-Meier survival curve showed that the 5-year overall survival rate in NSCLC with low expression of SGK1 was significantly higher than that in NSCLC with high expression of SGK1 (P ＜ 0.05).Conclusions The expression of SGK1 in tissues is closely related to the prognosis of patients with NSCLC.The high expression of SGK1 in tissues is not conducive to the prognosis of patients with NSCLC.
ABSTRACT
Objective To investigate the programming effects of glucocorticoids (GCs) exposure during rat pregnancy on the cardiac functions of adult offspring, so as to explore the cardiac protective effect of GCs and the underlying mechanisms. Methods Advanced pregnancy GCs exposure model was established with rats. The infarction degrees of myocardium of offspring rats were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining after ischemia-reperfusion (I/R) injury. The mRNA levels of cardio-protective factors serum- and glucocorticoid-regulated protein kinase 1(Sgk1), corticotropin-releasing hormone receptor 2 (Crhr2), urocortin (Ucn), and Ucn2 were determined by real-time PCR. The protein level of SGK1 was detected using Western blotting analysis. Bisulfite sequencing PCR (BSP) was employed to determine the methylation level of Sgk1 promoter. Results The body mass of the offsprings of GCs-exposed pregnant rats were significantly lower than that of the normal saline-injected pregnant rats (P<0.01). The ratio between infarction area and risk area of hearts after ischemia-reperfusion in the male adult offspring from GCs-exposed group was significantly larger than that from the vehicle group(P<0.01). The mRNA and protein levels of SGK1 were significantly decreased in male adult offspring hearts exposed to GCs prenatally (P<0.01, P<0.05), whereas Ucn and Ucn2 mRNA expressions were significantly decreased in the hearts of female adult offspring exposed to GCs prenatally (P<0.05). There were multiple CpG islands in Sgk1 promoter, with the proximal CpG island in the Sgk1 promoter being significantly hypermethylated in the heart of adult male offspring exposed to GCs during late pregnancy (P<0.01). Conclusion GCs exposure during pregnancy can cause programming effects on cardiac functions of male adult offspring in rats, probably via the down-regulation of SGK1 expression in the heart, which is largely due to the hypermethylation on Sgk1 promoter.