Prognostic significance of preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of patients with gastric cardia cancer.

AIM: To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA levels in peripheral blood of patients with gastric cardia cancer (GCC). METHODS: We detected the preoperative and postoperative mRNA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors. RESULTS: Elevated preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 mRNA, and preoperative and postoperative CEA mRNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status (P = 0.018), preoperative CK19 (P = 0.035) and CEA (P = 0.011) mRNA levels were independent prognostic factors for overall survival (OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively (P < 0.001). CONCLUSION: Elevated preoperative CK19 and CEA mRNA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.

Association of Kruppel-like factor 4 expression with the prognosis of esophageal squamous cell carcinoma patients.

OBJECTIVE: To investigate the association of Kruppel-like factor 4 (KLF4) expressions with the prognosis of esophageal squamous cell carcinoma (SCC) patients. METHODS: Ninety-eight cases of esophageal carcinoma patients were enrolled. The expression of KLF4 in the esophageal SCC and normal esophageal mucosa tissues were examined by immunohistochemistry. The correlations between the expression of KLF4 protein and patients' clinical characteristics and prognosis were analyzed. RESULTS: We observed higher expressed KLF4 in normal esophageal mucosa tissues than esophageal SCC tissues, with positive rate of 82.7% (81/98) and 43.8% (43/98) respectively. In patients with lymphatic metastasis, the positive rate of KLF4 was 24.4% (10/41), whereas it was 57.9% (33/57) in patients without lymphatic metastasis, and the difference was significant (x(2) = 10.871, P = 0.001). The positive rates of KLF4 were 62.5% (5/8), 53.1% (26/49) and 29.3% (12/41) in stage I, II and III patients, respectively. There were no correlations between the expression of KLF4 and gender, age, tumor size, location, differentiation grade and infiltration depth. The 5-year survival rates and median survival times were 48.8% and 25.5%, and 55 and 26 months for the patients with KLF4 positive and negative expression, respectively. There were significant differences between the patients with KLF4 positive expression and negative expression in the 5-year survival rates and median survival times (x(2) = 5.747 and 4.493, P = 0.017 and 0.034). CONCLUSION: KLF4 might act as a tumor suppressor in esophageal SCC and the expression status of KLF4 could be considered as a prognosis predictor for esophageal SCC patients.

Extranodal metastasis is a powerful prognostic factor in patients with adenocarcinoma of the esophagogastric junction.

BACKGROUND AND OBJECTIVES: The purpose of this study is to estimate the effect of extranodal metastasis (EM) on recurrence and survival in patients with adenocarcinoma of the esophagogastric junction (AEG) after curative resection. METHODS: Clinical data from 284 node-positive AEG patients who underwent curative resection were reviewed. Univariate and multivariate analyses were conducted to elucidate the effect of EM on recurrence-free survival (RFS) and overall survival (OS). RESULTS: EM was detected in 70 (24.6%) of the 284 cases. It had a significant correlation with tumor size, Lauren type, histopathological grading, depth of tumor invasion, number of metastatic nodes, lymph node ratio, and TNM stage. The 5-year RFS and OS rates were 22.2% and 24.3%, respectively. Patients with EM had a significantly decreased RFS (16 vs. 36 months, P < 0.001) and OS (23 vs. 41 months, P < 0.001) compared with those without EM. Multivariate analyses identified EM as an independent prognostic factor (P = 0.003 and 0.001, respectively). CONCLUSION: The presence of EM increases recurrence probability and reduces OS probability of AEG patients with lymph node metastasis. EM is a powerful prognostic factor reflecting a particularly aggressive biological behavior. Better understanding of EM status can help clinicians with regard to treatment decision and prognosis evaluation.

[Clinical significance of serum high-mobility group box 1 detection in esophageal squamous cell carcinoma].

OBJECTIVE: To explore the level of serum high-mobility group box 1 (HMGB1) in patients with esophageal squamous cell carcinoma (ESCC) and the feasibility of HMGB1 as a tumor marker. METHODS: Serum HMGB1, carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (Cyfra21-1) and squamous cell carcinoma antigen (SCC) were measured by enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassay (ECLIA) and microparticle enzyme immunoassay (MEIA) respectively in 78 patients with ESCC preoperatively as well as a month after esophagectomy. At the same time, serum HMGB1, CEA, Cyfra21-1 and SCC of 60 healthy adult volunteers were detected with the same method. The unilateral P95 value of serum HMGB1 (>96 µg/L) was defined as positive. According to the Roche kit diagnostic criteria, CEA>5.0 µg/L, Cyfra21-1>3.3 µg/L and SCC>1.5 µg/L were defined as positive. RESULTS: The preoperative positive ratio of serum HMGB1 in 78 patients with ESCC was 84.6%, and the level of serum HMGB1 was associated with the tumor size, infiltration depth, lymph node metastasis and tumor stage (P<0.01 or P<0.05). One month after esophagectomy, the level of serum HMGB1 in ESCC declined significantly compared with the preoperative level (P<0.01), and the level of serum HMGB1 in T4, N1, stage III was higher compared to corresponding T, N and tumor stage (P<0.01 or P<0.05). The positive ratio of CEA, Cyfra21-1 and SCC was 10.3%, 25.6% and 42.3% respectively in 78 ESCC patients preoperatively, so the sensitivity of these tumor markers was lower. One month after esophagectomy, serum Cyfra21-1 and serum SCC were significantly decreased compared to the preoperative level (P<0.01). However, there was no significant difference of preoperative serum CEA compared to a month after esophagectomy in ESCC (P>0.05). The specificity of HMGB1, CEA, Cyfra21-1 and SCC were 93.3%, 88.3%, 90.0% and 93.3% respectively. CONCLUSION: Compared to CEA, Cyfra21-1 and SCC, serum HMGB1 in ESCC patients is easier for detection and its sensitivity and specificity are higher, which may be used as a marker in diagnosis, prediction of prognosis and monitor of postoperative recurrence of ESCC.

[Effect of HMGB1 on the VEGF-C expression and proliferation of esophageal squamous cancer cells].

OBJECTIVE: To explore the effect of HMGB1 on the VEGF-C expression and proliferation of esophageal squamous cancer cells as well as its possible mechanism. METHODS: A cassette encoding siRNA targeting HMGB1 mediated by rAAV was constructed, the rAAV-siHMGB1-hrGFP, and a vector encoding siRNA mismatching HMGB1 was constructed, the rAAV-miHMGB1-hrGFP. This experiment in vitro included three groups, namely, the blank control group (group A) of KYSE150 cells transfected by rAAV-hrGFP, negative mismatch control group (group B) of KYSE150 cells transfected with rAAV-miHMGB1-hrGFP, and RNA interference group (group C) of KYSE150 cells transfected with rAAV-siHMGB1-hrGFP. We examined the expression of HMGB1 mRNA and protein in the three group cells by real-time PCR and Western blot after 24 h and 48 h, respectively. Then, VEGF-C expression and cell proliferation in the three group cells with or without sRAGE, as an inhibitor of RAGE signal pathway, were assayed by ELISA and MTT after 24 h. RESULTS: The expression of HMGB1 mRNA and protein in KYSE150 cells in vitro in the group C transfected with rAAV-siHMGB1-hrGFP at the final concentration of 2×10(6) v.g/cell was significantly lower than that of the group A or B after 24 h and 48 h (P < 0.01). The VEGF-C expression of KYSE150 cells was (502.43 ± 13.10) pg/ml in the group C, significantly reduced in comparison with that of the group A (686.40 ± 10.94) pg/ml or group B (682.31 ± 9.61) pg/ml after 24 h (P < 0.05). At the same time, the proliferation of KYSE150 cells in the group C was significantly inhibited compared with that of groups A and B after 24 h (P < 0.01). Moreover, sRAGE at the final concentration of 0.2 µg/ml inhibited the VEGF-C expression and proliferation of KYSE150 cells compared with the corresponding group without sRAGE after 24 h (P < 0.01 or P < 0.05). However, there was no significant difference of the VEGF-C expression and proliferation of KYSE150 cells with sRAGE in the group C compared with that of cells with sRAGE of the group A or group B after 24 h (P > 0.05). CONCLUSIONS: In esophageal squamous cell carcinoma, HMGB1 can promote the VEGF-C expression and proliferation of the cancer cells through RAGE signal pathway, and HMGB1-RAGE may become a potential target for cell proliferation and lymph node metastasis of this cancer.