G2 and S phase-expressed-1 induces chromosomal instability in esophageal squamous cell carcinoma cells and inhibits cell apoptosis through ROS/JNK signaling.

New diagnostic and therapeutic strategies are urgently needed to improve the prognosis of patients with esophageal squamous cell carcinoma (ESCC), which has high morbidity and mortality. Bioinformatics analysis revealed that cell cycle regulation related molecular G2 and S phase-expressed-1 (GTSE1) was dysregulated in ESCC. In this study, the ectopic expression of GTSE1 was verified in ESCC patients' tissues and cell lines. After overexpression or knockdown of GTSE1 using lentiviral transfection, the effects of GTSE1 on the proliferation, migration, invasion, and apoptosis of ESCC cells were detected. The contribution of GTSE1 in inducing chromosomal missegregation in cells leading to chromosome instability (CIN) has been described. Long-term existence of CIN can increase reactive oxygen species (ROS) generation in ESCC cells, followed by inhibition of apoptosis by activating the c-Jun N-terminal kinase (JNK) signaling pathway, and this inhibition could be relieved after treatment with JNK inhibitor. In vivo experiments, we also confirmed the tumor-promoting effect and mechanism of GTSE1 in ESCC using nude mice model. In this study, we demonstrated that GTSE1 induces CIN in ESCC cells, and increases intracellular ROS production, which leads to cellular oxidative stress, contributes to the activation of the JNK signaling pathway, and thereby inhibits apoptosis leading to ESCC tumorigenesis.

Aspirin Exerts Its Antitumor Effect in Esophageal Squamous Cell Carcinoma by Downregulating the Expression of ATAD2 and KIF4A.

Objective: To investigate the expression of ATPase family AAA domain-containing protein 2 (ATAD2) and kinesin family member 4A (KIF4A) in esophageal squamous cell carcinoma (ESCC) tissues and their association with clinicopathological features and to explore the role of ATAD2 in regulating KIF4A expression and biological functions in ESCC cells and the effect of aspirin on their expression. Methods: The mRNA and protein expression of ATAD2 and KIF4A in the tissues of patients with ESCC were measured by RT-qPCR and immunohistochemistry, and the correlation between the expression of mRNA and clinicopathological characteristics was analyzed. Western blot and RT-qPCR were used to detect the interference efficiency and KIF4A expression after si-ATAD2 transfection in EC109 and KYSE30 cells. CCK-8 and Transwell assay were performed to investigate the effects of ATAD2 and aspirin on proliferation, migration, and invasion of ESCC cells. The effect of aspirin on the expression of ATAD2 and KIF4A in ESCC cells was measured by RT-qPCR and Western blot. Results: The expression of ATAD2 and KIF4A was upregulated in ESCC tissues, and both were correlated with the differentiation grades and lymph node metastasis. Knockdown of ATAD2 in ESCC cells significantly inhibited cell proliferation, migration, and invasion. Compared to the negative control group, the proliferation, migration, and invasion ability of ESCC cells in the aspirin-treated groups were decreased, and the expression of ATAD2 and KIF4A in ESCC cells was decreased after treating with aspirin for 48 h. Conclusion: The expression levels of ATAD2 and KIF4A are elevated in ESCC. ATAD2 promotes proliferation, migration, and invasion of ESCC cells by regulating KIF4A. Aspirin can inhibit the malignant behavior of ESCC cells by downregulating ATAD2 and KIF4A.

Characterization of E-cadherin expression in normal mucosa, dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis.

BACKGROUND: Gastric cardia adenocarcinoma (GCA), which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries, is of similar geographic distribution with esophageal squamous cell carcinoma in China, and even referred as "sister cancer" by Chinese oncologists. The molecular mechanism for GCA is largely unknown. Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers. However, the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis. AIM: To characterize E-cadherin expression in normal gastric cardia mucosa, dysplasia and GCA tissues, and its influence on prognosis for GCA. METHODS: A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases. The enrollment criteria included radical surgery for GCA, but without any radio- or chemo-therapy before operation. The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue (n = 208) and dysplasia lesions (n = 156) were collected, and processed as tissue microarray for immunohistochemistry. The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter, telephone or home interview. E-cadherin protein expression was determined by two step immunohistochemistry. Kaplan-Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients. RESULTS: Of the 4561 GCA patients, there were 3607 males with a mean age of 61.6 ± 8.8 and 954 females with a mean age of 61.9 ± 8.6 years, respectively. With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA, the positive immunostaining rates for E-cadherin decreased significantly from 100% to 93.0% and 84.1%, respectively (R2 = 0.9948). Furthermore, E-cadherin positive immunostaining rate was significantly higher in patients at early stage (0 and I) than in those at late stage (II and III) (92.7% vs 83.7%, P = 0.001). E-cadherin positive expression rate was significantly associated with degree of differentiation (P = 0.001) and invasion depth (P < 0.001). Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative (P = 0.026). It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis. However, in patients with negative lymph node metastasis, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.036). Similarly, in patients with late stage GCA, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.011). CONCLUSION: E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Long-term effect of hospital volume on the postoperative prognosis of 158,618 patients with esophageal squamous cell carcinoma in China.

Background: The impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I-III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China. Aim: To investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China. Methods: The date of 158,618 patients with ESCC were collected from a database (1973-2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality. Results: In both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both P<0.05). And high volume hospital was an independent factor for better prognosis in ESCC patients. The relationship between hospital volume and the risk of all-cause mortality was half-U-shaped, but overall, hospital volume was a protective factor for esophageal cancer patients after surgery (HR<1). The concentration of hospital volume associated with the lowest risk of all-cause mortality was 1027 cases/year in the overall enrolled patients. Conclusion: Hospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year. Core tip: Hospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery.

Characterization of 500 Chinese patients with cervical esophageal cancer by clinicopathological and treatment outcomes.

Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer (CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients. Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database (1973-2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments (radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan-Meier method were used to compare the continuous variables and survival. Results: Among the 500 CEC patients, 278 (55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients (99.2%) were diagnosed with squamous cell carcinoma. In 171 (34.2%) patients who received surgery, 22 (12.9%) had undergone laryngectomy. In 322 (64.4%) patients who received non-surgical treatments, 245 (76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy (P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.

Multiple actions of poly(ethylene octene) grafted with glycidyl methacrylate on the performance of poly(lactic acid).

Poly(ethylene octene) grafted with glycidyl methacrylate (POE-g-GMA) was employed to improve the rheological and thermal properties, toughness, and foaming behaviors of poly(lactic acid) (PLA) through a chain extension effect. The dynamic rheological properties of PLA were improved significantly with increasing content of POE-g-GMA, due to the chain extension reaction between PLA and POE-g-GMA. As the content of POE-g-GMA increased, the cold crystallization temperature of PLA decreased by more than 10 °C and the crystallinity of PLA increased slightly from 1.2% to 4.7%, respectively. The impact strength of PLA with a POE-g-GMA content of 10 wt% increased by more than 4 times, compared with that of pure PLA. A sea-island structure could be observed in the PLA/POE-g-GMA blends and the distribution of POE-g-GMA was uniform. PLA foams with various POE-g-GMA contents were prepared in a stainless-steel autoclave using supercritical CO2 as a physical blowing agent. The cellular morphology of PLA foam was obviously improved when the concentration of POE-g-GMA increased from 5 wt% to 10 wt%.

[Expression and significance of bone sialoprotein(BSP) in esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the roll of bone sialoprotein (BSP), a secreted glycoprotein, found in mineralized tissues in the development and progression of human esophageal squamous cell carcimoma (ESCC), and explore its association with clinicopathological characteristics and five-year survival of the patients. METHODS: The expression of BSP was determined in 211 primary ESCC tumors and their paired nontumorous tissues using tissue-array, RT-PCR and immunohistochemistry. RESULTS: Primary ESCC tissues showed a significantly higher expression rate of BSP mRNA than their paired nontumorous tissues (93.8% vs. 16.6%, P < 0.001), the same with BSP protein (56.9% vs. 31.3%, P < 0.001). The expression rate of BSP protein was correlated to lymph node metastasis and TNM stage (P < 0.05). The 5-year survival rate of BSP protein-positive ESCC patients was significantly lower than that of BSP protein-negative ESCC patients (P < 0.05). Multivariate analysis showed that tumor differentiation, TNM staging and BSP protein expression were independent factors affecting the prognosis of ESCC patients (P < 0.05). CONCLUSIONS: The abnormal expression of BSP may play a significant role in the malignant progression and prognosis of ESCC, and BSP might be a marker reflecting the biologial behavior of ESCC.