Lv Ji

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.

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.

Effects of neoadjuvant radiochemotherapy on pathological staging and prognosis for locally advanced esophageal squamous cell carcinoma

The role of neoadjuvant therapy in the treatment of locally advanced esophageal carcinoma still remains controversial. The aim of this study was to evaluate the effects of neoadjuvant radiochemotherapy on pathological staging and prognosis in the patients with locally advanced esophageal squamous cell carcinoma. Between January 1991 and December 2000, 473 patients with advanced esophageal carcinoma diagnosed by endoscopic biopsy underwent surgical resection in our center. With informed consent, they were randomized into four groups: neoadjuvant chemotherapy, neoadjuvant radiotherapy, neoadjuvant radiochemotherapy, and surgery alone (control group). The preoperative computed tomography staging criteria were the following: Stage I, the tumor limited to the esophageal lumen or the thickness of the esophageal wall varied between 3-5 mm; Stage II, the thickness exceeds 5 mm but no invasion to the mediastinum or distant metastasis; Stage III, the tumor invades adjacent mediastinal structure; and Stage IV, there is distant metastasis. The tumor resection rate, pathological stage, treatment-related complication, and survival among groups were compared. The radical resection rate for the patients in radiotherapy and radiochemotherapy groups was increased in comparison with the control group (P < 0.05). Their pathological stage after esophagectomy was regressed significantly than that of the control group (50.85%, 55.08% vs. 0%, P < 0.05). The adjuvant chemotherapy group did show significant improvement on resection rate and pathological staging compared with the control group. The treatment-related complication in the three neoadjuvant groups had no significant difference from that of the control group (P > 0.05). The 3-year survival rate of radiotherapy and radiochemotherapy groups were significantly higher than that of the control group (69.49%, 73.73% vs. 53.38%, P < 0.05). The 5-year survival rate of radiochemotherapy group was higher than that of the radiotherapy group although did not show a statistical difference (P > 0.05). Rational application of neoadjuvant radiochemotherapy seems to provide a modest benefit in radical resection and survival in patients with locally advanced esophageal carcinoma.

Overexpression of KPNA2 correlates with poor prognosis in patients with gastric adenocarcinoma

This study aims to investigate the expression and significance of KPNA2 in human gastric adenocarcinoma progression and prognosis. Using immunohistochemistry and real-time reverse transcriptase polymerase chain reaction assay, we identified abnormally elevated expression of KPNA2 in gastric adenocarcinoma tissues compared to paired normal stomach mucosa tissues in 30 patients (p < 0.05). In order to investigate the correlations between KPNA2 and the clinicopathological features of gastric adenocarcinoma, the expression of KPNA2 in 142 patients with gastric adenocarcinoma was detected by immunohistochemistry, and the results showed that overexpression of KPNA2 was associated with the size of tumor (p < 0.001), histological grade (p < 0.001), lymph node involvement (p = 0.001), and tumor node metastasis stage (p < 0.001). Kaplan–Meier survival analysis showed that patients with high KPNA2 expression showed a significantly shorter overall survival time compared with patients with low KPNA2 expression. Multivariate analysis suggested that KPNA2 expression might be an independent prognostic indicator (p < 0.001) for the survival of patients with gastric adenocarcinoma. In conclusion, overexpression of KPNA2 is closely related to progression of gastric adenocarcinoma and might be regarded as an independent predictor of poor prognosis for gastric adenocarcinoma.

Association of Wnt1/β-Catenin with Clinical Pathological Characteristics and Prognosis of Esophageal Squamous Cell Carcinoma

The aim of this study was to investigate the correlation between Wnt1/beta-catenin expression and the clinicopathologic features and prognosis of patients with esophageal squamous cell carcinoma (ESCC). The mRNA and protein expression levels of Wnt1/beta-catenin genes in 70 ESCC and 15 adjacent noncancerous paraffin-embedded samples were determined by real-time quantitative polymerase chain reaction and immunohistochemical staining. The mRNA expression level of Wnt1/beta-catenin in ESCC was significantly higher than that in the adjacent noncancerous tissues (1.9934 +/- 1.9888 vs. 0.8863 +/- 0.665, p = 0.0184; 0.2854 +/- 0.1298 vs. 0.0128 +/- 0.0158, p = 0.0000, respectively), and the overexpression of Wnt1/beta-catenin mRNA was aggressively associated with lymph node metastasis and advanced pathological stage (p < 0.0001). The protein expression level of Wnt1/beta-catenin was also significantly higher than that in the adjacent noncancerous tissues (0.3830 +/- 0.0947 vs. 0.2721 +/- 0.1474, p = 0.0002; 0.2835 +/- 0.0844 vs. 0.2352 +/- 0.0670, p = 0.0210, respectively); however, the overexpression was not associated with clinicopathologic characteristics. Meanwhile, the protein expression level of Wnt1 had no relevance with that of beta-catenin. The overexpression of Wnt1/beta-catenin might be an important molecular marker to predict the clinicopathologic stage and prognosis of ESCC, and the level of Wnt1/beta-catenin mRNA was conversely correlated with lymph node metastasis and advanced pathological stage. The overexpression of Wnt1/beta-catenin mRNA should also predict poor prognosis of ESCC; however, it might not be an independent prognostic factor.