Circ-DLG1 promotes the proliferation of esophageal squamous cell carcinoma.

BACKGROUND: Circular RNAs (circRNAs) are a class of noncoding RNAs with closed loop structures. There has been growing evidence showing that circRNAs are involved in the pathogenesis of human diseases including various carcinomas. Our study is aimed to investigate the association between a new circRNA named circ-DLG1 (hsa_circ_0007203) and esophageal squamous cell carcinoma (ESCC) carcinogenesis. METHODS: The circ-DLG1 expression levels were detected by real-time quantitative reverse transcription-polymerase chain reaction in cells, tissues, and plasmas. The correlation between circ-DLG1 expression and clinicopathologic features was then analyzed. The effect of circ-DLG1 expression on cell proliferation was evaluated in vitro by CCK8 assay and clone formation experiment. Finally, a network of circ-DLG1 with its targeted miRNA interactions and corresponding mRNAs was constructed. RESULTS: circ-DLG1was found to be significantly upregulated in ESCC cells, tissues, and plasmas compared to normal cases. Furthermore, in vitro assays, TE10 and KYSE180, of the ESCC cell lines demonstrated that knockdown of circ-DLG1 reduced cell proliferation significantly. Prediction and annotation revealed that circ-DLG1 was able to sponge to 20 miRNAs and 60 corresponding target mRNAs. CONCLUSION: Our study indicated that upregulation of circ-DLG1 promoted esophageal cell proliferation ability and might serve as a novel biomarker for ESCC.

Down-regulation of circPVRL3 promotes the proliferation and migration of gastric cancer cells.

Circular RNA (circRNA) is a key regulator in the development and progression of various types of carcinomas. However, its role in gastric cancer (GC) tumorigenesis is not well understood. The present study aimed to investigate the expression profile and potential modulation of circRNAs on GC carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in GC tissue. Results showed that a decrease in the circPVRL3 expression level was associated with the presence of GC, and also with higher TNM stage and lower overall survival rates compared with that in adjacent noncancerous tissues. In vitro assays of the GC cell lines MKN-45 and MGC-803 demonstrated that knockdown of circPVRL3 promoted cell proliferation significantly. Prediction and annotation revealed circPVRL3 was able to sponge to 9 miRNAs and may be also able to have a binding with AGO2, FUS, LIN28A, PTB, and EIF4A3. In addition, based on the structure of internal ribosomal entry sites, open reading frame, and m6A modification, circPVRL3 may have the potential ability to encode proteins. Taken together, our study indicated that down-regulation of circPVRL3 could promote the proliferation in gastric carcinoma and have potential to encode protein.

Upregulation of MAGEA4 correlates with poor prognosis in patients with early stage of esophageal squamous cell carcinoma.

Esophageal cancer is a common type of cancer in the People's Republic of China. Many genes have been reported to be linked with it. Melanoma antigen gene family A (MAGEA) genes are frequently highly expressed in various types of carcinoma. However, the specific role of MAGEA gene expression in esophageal squamous cell carcinoma (ESCC) still remains unclear. MAGEA4 is a member of MAGEA genes. We aimed to investigate the expression and prognosis of MAGEA4 expression in ESCC. MAGEA4 messenger RNA expression levels of 120 pairs of tumor and nontumor tissues of patients with ESCC were measured by quantitative real-time polymerase chain reaction. The results showed that MAGEA4 messenger RNA was significantly elevated in tumor tissues of patients with ESCC compared to nontumor ones. In addition, overexpression of MAGEA4 messenger RNA was significantly correlated with poorer overall survival (P=0.018) in early stage of patients with ESCC (I-IIA). In conclusion, MAGEA4 played an important role in the early stage of ESCC and overexpression of MAGEA4 was expected to become a potential prognostic marker for patients with early stage of ESCC.

Implication of lncRNAs in pathogenesis of esophageal cancer.

Long non-coding RNAs (lncRNAs), transcripts as longer than 200 nt in length with a great number of varieties in human genomics, play important roles in the regulation of genetics and epigenetics including gene transcription and post-transcription. Increasing evidence have demonstrated the upregulation of lncRNAs in tumorigenesis and metastasis of esophageal cancer (EC), a type of malignant tumors particularly in Asia. In this review, we briefly discuss the profiles and functions of lncRNAs involved in the progression of EC, which may provide a new approach to improve EC diagnosis and treatment.

The Prognostic Impact of Heat Shock Proteins Expression in Patients with Esophageal Cancer: A Meta-Analysis.

PURPOSE: Heat shock proteins (HSPs) are highly conserved molecular chaperones. There are various studies that assess the prognostic value of HSPs in patients with esophageal cancer, but the conclusion remains controversial. This is the first meta-analysis study aiming to summarize the evidence on the suitability of HSPs to predict patients' survival. MATERIALS AND METHODS: Searching PubMed, Web of science and Medline until May 31, 2014, data were compared for overall survival in patients with down-regulated HSPs level with those with up-regulated level. We conducted a meta-analysis of 9 studies (801 patients) that correlated HSPs levels with overall survival. Data were synthesized with hazard ratios (HRs). RESULTS: The estimated risk of death was 2.93-fold greater in HSP27 negative patients than HSP27 positive patients [95% confidence interval (CI), 1.12-7.62]. When limited to esophageal squamous cell carcinoma (ESCC), the risk of death in HSP27 negative patients seemed more significant (HR, 3.90; 95% CI, 2.35-6.49). Decreased expression of HSP70 was also associated with worse survival in esophageal cancer (HR, 2.83; 95% CI, 1.90-4.23) and, when limited to ESCC, HR was 3.21 (95% CI, 1.94-5.30). Data collected, however, were not sufficient to determine the prognostic value of HSP90 in patients with ESCC nor esophageal adenocarcinomas (EADC). CONCLUSION: In this meta-analysis, reduced HSP27 and HSP70 expressions were associated with poor survival in patients with esophageal cancer, especially esophageal squamous cell carcinoma.

Upregulation of the long noncoding RNA PCAT-1 correlates with advanced clinical stage and poor prognosis in esophageal squamous carcinoma.

Recent studies reveal that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. Prostate cancer-associated ncRNA transcript 1 (PCAT-1) is one of the lncRNAs involved in cell apoptosis and proliferation of prostate cancer. This study aimed to assess the potential role of PCAT-1 specifically in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PCAT-1 in matched cancerous tissues and adjacent noncancerous tissues from 130 patients with ESCC, 34 patients with non-small cell lung cancer (NSCLC), and 30 patients with gastric carcinoma (GC). The correlation of PCAT-1 with clinicopathological features and prognosis were also analyzed. The expression of PCAT-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (70.8%, p < 0.01), and the high level of PCAT-1 expression was significantly correlated with invasion of the tumor (p = 0.024), advanced clinical stage (p = 0.003), lymph node metastasis (p = 0.032), and poor prognosis. However, PCAT-1 mRNA expression had no significant difference between paired primary cancerous tissues and the adjacent noncancerous tissues in 34 cases of NSCLC (p = 0.293) and 30 cases of GC (p = 0.125). High expression of PCAT-1 was specifically correlated with invasion of cancer tissues, metastasis of lymph node, and advanced tumor stage of ESCC. High expression of PCAT-1 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Adjuvant therapy targeting PCAT-1 molecule might be effective in treatment of ESCC.

MicroRNA-206 attenuates tumor proliferation and migration involving the downregulation of NOTCH3 in colorectal cancer.

Colorectal cancer (CRC) is the most common cancer diagnosed worldwide, and the development of metastases is a major cause of mortality. Accumulating evidence suggests that microRNAs are important in carcinogenesis by affecting the expression of genes that regulate cancer progression. A number of studies have shown that miR-206 is frequently downregulated in many human malignancies, including CRC, and is associated with a more malignant phenotype. Previous studies involving HeLa and C2C12 cells have validated the inhibitory mechanism of miR-206 via NOTCH3 targeting. However, whether or not the interplay between miR-206 and NOTCH3 also occurs in CRC is unknown. Therefore, we investigated the tumor suppressive and metastatic effects of miR-206 and its target, NOTCH3, in CRC. Based on the inverse association between the expression of miR-206 and NOTCH3 in CRC tissues, miR-206 mimics were transiently transfected into the SW480 (and its metastatic strain) and SW620 colon cancer cell lines. Upregulation of miR-206 inhibited cancer cell prolife-ration and migration, blocked the cell cycle, and activated apoptosis. The tumor suppressive capacity of miR-206 had a similar effect on CRC cells, although with a different metastatic potential, and may be explained by direct NOTCH3 signaling inhibition and indirect cross-talk with other signaling pathways involving CDH2 and MMP-9. These results support miR-206 as a tumor suppressor in CRC and suggest a potential therapeutic target for clinical intervention.

Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (lncRNAs) were present in the blood of cancer patients and have shown great potential as powerful and non-invasive tumor markers. However, little is known about the value of lncRNAs in the diagnosis of esophageal squamous cell carcinoma (ESCC). We hypothesized that ESCC-related lncRNAs might be released into the circulation during tumor initiation and could be utilized to detect and monitor ESCC. METHODS: Ten lncRNAs (HOTAIR, AFAP1-AS1, POU3F3, HNF1A-AS1, 91H, PlncRNA1, SPRY4-IT1, ENST00000435885.1, XLOC_013104 and ENST00000547963.1) which previously found to be differently expressed in esophageal cancer were selected as candidate targets for subsequent circulating lncRNA assay. A four-stage exploratory study was conducted to test the hypothesis: (1) optimization of detected method to accurately and reproducibly measure ESCC-related lncRNAs in plasma and serum; (2) evaluation of the stability of circulating lncRNAs in human plasma or serum; (3) exploration the origin of ESCC-related lncRNAs in vitro and in vivo; (4) evaluation the diagnostic power of circulating lncRNAs for ESCC. RESULTS: ESCC-related lncRNAs were detectable and stable in plasma of cancer patients, and derived largely from ESCC tumor cells. Furthermore, plasma levels of POU3F3, HNF1A-AS1 and SPRY4-IT1 were significantly higher in ESCC patients compared with normal controls. By receiver operating characteristic curve (ROC) analysis, among the three lncRNAs investigated, plasma POU3F3 provided the highest diagnostic performance for detection of ESCC (the area under the ROC curve (AUC), 0.842; p < 0.001; sensitivity, 72.8%; specificity, 89.4%). Moreover, use of POU3F3 and SCCA in combination could provide a more effective diagnosis performance (AUC, 0.926, p < 0.001, sensitivity, 85.7%; specificity, 81.4%). Most importantly, this combination was effective to detect ESCC at an early stage (80.8%). CONCLUSIONS: Plasma POU3F3 could serve as a potential biomarker for diagnosis of ESCC, and the combination of POU3F3 and SCCA was more efficient for ESCC detection, in particular for early tumor screening.

Association of decreased expression of long non-coding RNA LOC285194 with chemoradiotherapy resistance and poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Expression of the long non-coding RNA (lncRNA) LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of the present study was to explore the relationship between LOC285194 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC), so as to assess whether it could be a novel biomarker for prognosis and prediction of response to therapy on ESCC patients. METHODS: The method of quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure LOC285194 expression in pretreatment biopsy specimens and matched normal tissue derived from ESCC patients who underwent preoperative chemoradiotherapy followed by surgical resection (CRT + S group; n = 55) or from those who received surgical resection alone (S group; n = 87). The association between LOC285194 expression and clinicopathological features and prognosis were then analyzed. RESULTS: LOC285194 expression was significantly down-regulated in ESCC tumor tissues when compared with the adjacent normal tissues (p < 0.001). Low expression of LOC285194 was associated with larger tumor size (p = 0.002), advanced TNM stage (p = 0.018), more lymph node metastases (p = 0.013) and distant metastases (p = 0.015). In the CRT + S group, the pathological complete response rate was 57% (16/28) for the LOC285194-high group, and 15% (4/27) for the LOC285194-low group. Univariate analysis revealed that low expression of LOC285194 was significantly correlated with CRT response (p = 0.002). Moreover, Kaplan-Meier survival analysis revealed that patients with low expression of LOC285194 had a decreased disease free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Multivariable analysis further identified low expression of LOC285194 as an independent prognosis factor for CRT response (p = 0.011), DFS (p < 0.001) and OS (p = 0.002). CONCLUSION: Decreased expression of LOC285194 could serve as a molecular marker to predict the clinical outcome of ESCC patients after surgery, and select patients who would benefit from preoperative CRT.

Comparison of long non­coding RNAs, microRNAs and messenger RNAs involved in initiation and progression of esophageal squamous cell carcinoma.

Traditionally, cancer research has focused on protein­coding genes, which are considered the principal effectors and regulators of tumorigenesis. Non­coding RNAs, in particular microRNAs (miRNAs) and long non­coding RNAs (lncRNAs), have been widely reported to be important in the regulation of tumorigenesis and cancer development. However, to the best of our knowledge, investigation of the expression profiles of lncRNAs and a comparison of the involvement of lncRNAs, miRNAs and messenger RNAs (mRNAs) in esophageal tumorigenesis and development have not previously been performed. In the current study, intrinsic associations among the expression profiles of lncRNAs, miRNAs and mRNAs from normal esophageal tissues and those from cancer tissues were investigated. Oligonucleotide microarrays were used to detect the expression profiles of the three types of RNA in the canceration processes of human esophageal squamous cell carcinoma (ESCC) tissues. It was demonstrated that the different RNAs exhibit associated patterns of expression among normal esophageal epithelium, low­grade intraepithelial neoplasia (LGIN), high­grade intraepithelial neoplasia (HGIN), and carcinoma tissues, particularly in the critical period of canceration (HGIN to ESCC). Furthermore, the results indicated a high level of similarity in the potential function of lncRNAs, miRNAs and mRNAs in the processes of ESCC development. In the current study, a first generation atlas of lncRNA profiling and its association with miRNAs and mRNAs in the canceration processes of ESCC were presented.

Long noncoding RNA SPRY4-IT1 is upregulated in esophageal squamous cell carcinoma and associated with poor prognosis.

LncRNA SPRY4-IT1 has been shown to promote the progression of melanoma. However, the role of lncRNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to investigate the clinical significance and biological functions of SPRY4-IT1 in ESCC. The expression levels of lncRNA SPRY4-IT in 92 ESCC patients and 8 ESCC cell lines were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in ESCC cell lines. Both in vitro and in vivo assays were performed to further explore its role in tumor progression. SPRY4-IT1 levels were significantly higher in ESCC tissues and cells than in corresponding adjacent noncancerous tissues and nontumorigenic esophageal epithelial cells, and the ESCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. The multivariate analysis revealed that SPRY4-IT1 expression level is an independent prognostic factor in ESCC patients. In vitro assays demonstrated that knockdown of SPRY4-IT1 reduced cell proliferation, invasiveness, and migration. In vivo assays demonstrated that knockdown of SPRY4-IT1 decreases cell growth. SPRY4-IT1 is a novel molecule involved in ESCC progression, which may provide a potential prognostic biomarker and a potential target for therapeutic intervention.

Upregulation of the long non-coding RNA PlncRNA-1 promotes esophageal squamous carcinoma cell proliferation and correlates with advanced clinical stage.

BACKGROUND: Recent studies revealed that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. PlncRNA-1 is one of lncRNAs that is associated with cell apoptosis and proliferation of prostate cancer. AIM: This study aimed to assess the potential role of PlncRNA-1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PlncRNA-1 in 73 pairs of ESCC and their matched normal tissues. The correlation of PlncRNA-1 with clinicopathological features and clinical stages was also analyzed. Cancer cell proliferation and apoptosis were assessed following knock-down of PlncRNA-1 by MTT, colony formation assay, and flow cytometry. RESULTS: The expression of PlncRNA-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (69.8 %, p < 0.05), and the high level of PlncRNA-1 expression was significantly correlated with advanced clinical stage (p < 0.01) and lymph node metastasis (p < 0.05). Furthermore, knockdown of PlncRNA-1 reduced cell proliferation and increased the apoptosis in vitro. CONCLUSIONS: PlncRNA-1 plays an important role in ESCC cell proliferation. Overexpression of PlncRNA-1 is correlated with advanced tumor stage and lymph node metastasis, and may serve as a potential prognostic marker and therapeutic target for ESCC.

Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis.

Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern of the lncRNA HOTAIR and assess its biological role in the development and progression of esophageal squamous cell carcinoma (ESCC), HOTAIR expression in ESCC tissues and adjacent noncancerous tissues were collected from 78 patients and measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). HOTAIR correlation with clinicopathological features and prognosis was also analyzed. Suppression of HOTAIR using siRNA treatment was performed in order to explore its role in tumor progression. Notably elevated HOTAIR expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (96%, P < 0.01), showing a high correlation with cancer metastasis (P < 0.01), elevated TNM (2009) stage classification (P < 0.01), and lowered overall survival rates (P = 0.003). Multivariate analysis revealed that HOTAIR expression (P = 0.003) is also an independent prognostic factor for comparison of TNM stage (P = 0.024) and lymph node metastasis (P = 0.010). Furthermore, in vitro assays of the ESCC cell line KYSE30 demonstrated that knockdown of HOTAIR reduced cell invasiveness and migration while increasing the response of cells to apoptosis. Thus, HOTAIR is a novel molecule involved in both ESCC progression and prognosis. Full elucidation of HOTAIR functionality relevant to ESCC may open avenues for the use of lncRNAs in identification of novel drug targets and therapies for ESCC and other prevalent cancers.

Composition, sources, and potential toxicology of polycyclic aromatic hydrocarbons (PAHs) in agricultural soils in Liaoning, People's Republic of China.

Surface soil (0-20 cm) samples (n = 143) were collected from vegetable, maize, and paddy farmland used for commercial crops in Liaoning, China. Sixteen priority polycyclic aromatic hydrocarbons (PAHs) listed in US Environmental Protection Agency were analyzed by high-performance liquid chromatography using a fluorescence detector. The soil concentrations of the 16 PAH ranged from 50 to 3,309 ng/g with a mean of 388 ng/g. The highest concentration of total PAHs found in soil of the vegetable farmland was 448 ng/g in average, followed by maize and paddy with total PAHs of 391 and 331 ng/g, respectively. Generally, the low molecular weight PAHs were more predominant than the high molecular weight PAHs in most of the soils. The evaluation of soil PAH contamination based on the Canadian criterion indicated that only naphthalene, phenanthrene, and pyrene were over the target values in several sampling sites. Isomer pair ratios and principal component analysis indicated that biomass and coal combustion were the main sources of PAHs in this area. And the average value of total B[a]Peq concentration in vegetable soils was higher than paddy and maize soils. We suggest that biomass burning should be abolished and commercial farming should be carried out far from the highways to ensure the safety of food products derived from commercial farming.

MiR-196a is upregulated in gastric cancer and promotes cell proliferation by downregulating p27(kip1).

Aberrant expression of miR-196a has been frequently reported in cancer studies. However, the expression and mechanism of its function in gastric cancer remains unclear. Quantitative real-time PCR was carried out to detect the relative expression of miR-196a in gastric cancer cell lines and tissues. SGC7901 cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cell proliferation. Higher expression of miR-196a in gastric cancer tissues was associated with tumor size, a higher clinical stage, and was also correlated with shorter overall survival of patients with gastric cancer. Exogenous downregulation of miR-196a expression significantly suppressed the in vitro cell-cycle progression, proliferation, and colony formation of gastric cancer cells, and ectopic miR-196a expression significantly enhanced the development of tumors in nude mice. Luciferase assays revealed that miR-196a inhibited p27(kip1) expression by targeting one binding site in the 3'-untranslated region (3'-UTR) of p27(kip1) mRNA. qPCR and Western blot assays verified that miR-196a reduced p27(kip1) expression at both mRNA and protein levels. The p27(kip1)-mediated repression in cell proliferation was reverted by exogenous miR-196a expression. A reverse correlation between miR-196a and p27(kip1) expression was noted in gastric cancer tissues. Our study shows that aberrant overexpression of miR-196a and consequent downregulation of p27(kip1) could contribute to gastric carcinogenesis and would be targets for gastric cancer therapies and further developed as potential prognostic factors.

Association of ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 with the prognosis of esophageal squamous cell carcinoma.

In our previous study, Human Signal Transduction in Cancer Gene Array was used in 12 fresh tumor samples to detect the gene expression profiles in the esophageal squamous cell carcinoma (ESCC) tissues matched adjacent non-cancerous samples. Among genes up-regulated at least twofold, ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 were found. So subsequently, the aim of this study was to investigate the prognosis and clinicopathologic roles of ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC tissue. The mRNA and protein expression levels of ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 genes in 70 ESCC and adjacent non-cancerous paraffin-embedded samples were determined by Real-Time Quantitative PCR (RT-PCR) and immunohistochemical staining. The mRNA expression level of ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 in ESCC was significantly higher than that in the adjacent non-cancerous tissues (0.0821 ± 0.0416 vs. 0.0185 ± 0.0201, P = 0.0000; 1.9934 ± 1.9888 vs. 0.8863 ± 0.665, P = 0.0184; 0.0298 ± 0.0215 vs. 0.0189 ± 0.0187, P = 0.0017; 2.098 ± 0.091 vs. 1.016 ± 0.078, P = 0.0000; 2.181 ± 2.158 vs. 0.931 ± 0.894, P = 0.0152; respectively), and the protein expression level of determined genes was also significantly higher than that in the adjacent non-cancerous tissues (0.2835 ± 0.0844 vs. 0.2352 ± 0.0670, P = 0.0003; 0.3830 ± 0.0947 vs. 0.2721 ± 0.1474, P = 0.0000; 0.2637 ± 0.0348 vs. 0.2042 ± 0.0180, P = 0.0000; 0.2058 ± 0.0316 vs. 0.1218 ± 0.0518, P = 0.0000; 0.2736 ± 0.0834 vs. 0.2251 ± 0.0571, P = 0.0001; respectively). Then, the overexpression of mRNA and protein levels of ß-catenin, Wnt1 and Bmi-1 was aggressively associated with lymph node metastasis, advanced pathological stage, and prognosis of the patients with ESCC (P < 0.05). The up-expression of Hoxa9 mRNA and protein was also aggressively associated with lymph node metastasis and advanced pathological stage (P < 0.05); however, the overexpression of Hoxa9 protein was not associated with the prognosis (P > 0.05). Meanwhile, the hypo-expression of Smad4 mRNA was aggressively associated with advanced pathological stage and prognosis of the patients with ESCC (P < 0.05); however, the hypo-expression of Smad4 protein was neutral to the prognosis and lymph node metastasis (P > 0.05). ß-catenin, Wnt1, Smad4, Hoxa9, and Bmi-1 protein expression analysis showed that the positive outcomes of the combined detection of Wnt1 and ß-catenin expression or Wnt1, ß-catenin and Bmi-1 expression were significantly worse than those of a single target protein expression (P < 0.05). Meantime, the prognosis of the combined positive expression of Wnt1, ß-catenin, and Bmi-1 was poorer than that in the combined positive expression of Wnt1 and ß-catenin (P < 0.05). The prognosis of ESCC patients with the overexpression of Wnt1/ß-catenin and Bmi-1 was relatively poor, and the level of Wnt1/ß-catenin and Bmi-1 was conversely correlated with advanced pathological stage and lymph node metastasis. The expression level of Smad4 and Hoxa9 mRNA was also associated with the prognosis of the patients with ESCC, pathological stage, and lymph node metastasis; however, they might not be the independent prognostic factor.

[A prospective comparison between surgery alone and postoperative chemoradiotherapy for locally advanced esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the role of postoperative chemoradiotherapy (CRT) as a multimodality treatment option for locally advanced thoracic esophageal squamous cell carcinoma (ESCC) by a prospective comparison between surgery alone and postoperative CRT. METHODS: Using preoperative computed tomography (CT)-based staging criteria, 158 patients with ESCC (stage II-III) were enrolled in this prospective study. With informed consent, the patients were randomized into two groups: postoperative CRT (78 cases) and surgery alone (S, 80 cases). After a few minor adjustments to the enrolled patients, the actual patients of postoperative CRT group and S group were 74 cases and 77 cases, respectively. Comparison of the complications, local recurrence rate, distant metastasis rate, survival rate and progression-free survival in the two groups was carried out. RESULTS: With a median follow-up of 37.5 months, the 1-, 3-, 5-, 10-year overall survival (OS) rates were 91.0%, 62.8%, 42.3%, 24.4% and 87.5%, 51.3%, 33.8%, 12.5% for the postoperative CRT and S arm, respectively. A significant difference in OS was detected between the two arms (P = 0.0276). There was a significant difference of progression-free survival (PFS) between the two arms (P = 0.0136). The local recurrence rates in the postoperative CRT group and S group were 14.9% and 36.4%, respectively (P < 0.05). No significant difference was detected between the complications of the two groups (P > 0.05). Toxicities of chemoradiotherapy in the postoperative CRT arm were moderate, which can be relieved rapidly by adequate therapy. CONCLUSION: Rational application of postoperative chemoradiotherapy can provide a benefit in progression-free survival and overall survival in patients with locally advanced esophageal squamous cell carcinoma.

[Operation combined with (125)I radioactive seeds implantation therapy on advanced esophageal squamous cell carcinoma].

OBJECTIVE: To evaluate the safety and efficacy of the united intraoperative (125)I seed implantation as a treatment option for thoracic advanced esophageal squamous cell carcinoma (ESCC). METHODS: From January 2000 to August 2004, according to preoperative CT staging criteria, 298 patients in phase II to III of ESCC had been enrolled in this prospective study. With informed consent, they were randomized into two groups: intraoperative (125)I seed implantation (group A) and surgery alone (group B). With 0.5 mCi of single seed, total activity in 10 to 30 mCi, matched peripheral dose in 60 to 70 Gy, 20 to 40 (125)I seeds were implanted into the target under direct vision in accordance with treatment planning system. The post-operative complications were observed. The validation and quality assessment of radioactive seeds were demonstrated according to CT scan or X imaging. The short-term efficacy was evaluated according to WHO criteria. The 1-, 3-, 5-, and 7-year survival rate were followed up. RESULTS: On the close date of August 31st 2008, the satisfied quality assessment of (125)I seeds was observed. There was no displacement or loss of seed. The local recurrence rates in the group A and group B were 14.9% and 38.7%, respectively, which were statistically significant (P < 0.05). The complete response and partial response rate in the group A was 78.8%. It was significantly higher than 30.3% in the group B (P < 0.05). There was no statistical difference among groups when comparing the complications (P > 0.05). The 1-year survival rates were no statistical difference among the two groups. However, the 3-, 5-, and 7-year survival rates in group A (64.0%, 42.7%, and 25.1%) were statistically different from that in the B group (52.0%, 34.5%, and 12.6%) (P < 0.05). CONCLUSIONS: It is safe, effective and simple application about the intraoperative (125)I seed implantation for advanced ESCC. It may reduce the local recurrence rate and improve survival.