LINC00963 promotes the malignancy and metastasis of lung adenocarcinoma by stabilizing Zeb1 and exosomes-induced M2 macrophage polarization.

BACKGROUND: Long intergenic non-coding RNA 00963 (LINC00963) is an oncogenic lncRNA in human cancers. However, little is known on how it impacts the pathogenesis of lung adenocarcinoma (LUAD). METHODS: Biological effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were examined by CCK-8, colony formation, EdU incorporation, transwell, and immunofluorescence assays, respectively. Macrophage polarization was evaluated by flow cytometry. Ubiquitination of Zeb1 was examined by co-immunoprecipitation. The location of LINC00963 in LUAD tissues and cell lines was tested by FISH assay. The LINC00963/HNRNPA2B1/Siah1 mRNA complex interaction was verified using RNA pull-down and immunoprecipitation assays. The exact roles of LINC00963 were further validated in metastasis and xenograft models. RESULTS: Higher LINC00963 expression in LUAD patients positively correlated with shorter overall survival, higher stages, and metastasis. LINC00963 mainly localized in the cytoplasm and aggravated malignant phenotypes of LUAD cells in vitro and metastasis in vivo. Mechanistically, LINC00963 directly interacted HNRNPA2B1 protein to trigger the degradation of Siah1 mRNA, which inhibited the ubiquitination and degradation of Zeb1. Moreover, exosomal LINC00963 derived from LUAD cells induced M2 macrophage polarization and promoted LUAD growth and metastasis. CONCLUSION: By stabilizing Zeb1 in cancer cells and delivering exosomes to induce M2 macrophage polarization, LINC00963 promoted the malignancy and metastasis of LUAD. Targeting LINC00963 may become a valuable therapeutic target for LUAD.

LncRNA ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of lung adenocarcinoma.

BACKGROUND: Growing evidence suggests that suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) is an oncogenic long noncoding RNA (lncRNA). However, little is known on its clinical significance, biological functions, or molecular mechanisms in lung adenocarcinoma (LUAD). METHODS: The expression of ST7-AS1 and miR-181b-5p were examined by qRT-PCR. The correlations between ST7-AS1 level and different clinicopathological features were analysed. In vitro, LUAD cells were examined for cell viability, migration and invasion by MTT, wound healing and Transwell assay, respectively. Epithelial-mesenchymal transition (EMT) biomarkers were detected by Western blot. The regulations between ST7-AS1, miR-181b-5p, and KPNA4 were examined by luciferase assay, RNA immunoprecipitation, RNA pulldown. Both gain- and loss-of-function strategies were used to assess the importance of different signalling molecules in malignant phenotypes of LUAD cells. The in vivo effect was analysed using the xenograft and the experimental metastasis mouse models. RESULTS: ST7-AS1 was upregulated in LUAD tissues or cell lines, correlated with tumours of positive lymph node metastasis or higher TNM stages, and associated with shorter overall survival of LUAD patients. ST7-AS1 essentially maintained the viability, migration, invasion, and EMT of LUAD cells. The oncogenic activities of ST7-AS1 were accomplished by sponging miR-181b-5p and releasing the suppression of the latter on KPNA4. In LUAD tissues, ST7-AS1 level positively correlated with that of KPNA4 and negatively with miR-181b-5p level. In vivo, targeting ST7-AS1 significantly inhibited xenograft growth and metastasis. CONCLUSIONS: ST7-AS1, by regulating miR-181b-5p/KPNA4 axis, promotes the malignancy of LUAD cells. Targeting ST7-AS1 and KPNA4 or up-regulating miR-181b-5p, therefore, may benefit the treatment of LUAD.

CD51 is an independent unfavorable prognostic factor in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common cancer in East Asia and some other parts of the world with a dismal prognosis. CD51 (integrin αv),a transmembrane glycoprotein responsible for cell-to-matrix binding has been found to enhance tumor progression. However, its expression and clinicopathological significance in ESCC tumors are not fully understood. The purpose of this study was to investigate the expression level of CD51 and to explore its clinicopathological significance in ESCC. METHODS: The expression of CD51 in 122 ESCC samples was examined by immunohistochemistry and its clinicopathological significance was evaluated. RESULTS: The expression of CD51 was observed in tumor cell membrane and/or cytoplasm, with a positive rate of 48.36% (59/122). High expression of CD51 was significantly associated with lymph node metastasis (P =  0.031), tumor size (P =  0.028) and invasive depth (P =  0.027). Kaplan-Meier analysis revealed that positive expression of CD51 was correlated with poor overall survival of ESCC patients (P =  0.015). Multivariate analysis suggested that CD51 was an independent prognositic factor for ESCC (hazard ration = 1.604; 95% CI, 1.086-2.368; P =  0.017). CONCLUSION: These data suggested CD51 was a predictor for the prognosis of ESCC patients.

Observation of clinical efficacy of application of enhanced recovery after surgery in perioperative period on esophageal carcinoma patients.

PURPOSE: To observe the clinical efficacy of the application of enhanced recovery after surgery (ERAS) in the perioperative period of esophageal carcinoma patients. METHODS: A total of 114 patients who were admitted to Affiliated Hospital of Jining Medical University for surgical treatment of esophageal carcinoma between June 2012 and June 2016 were enrolled and randomly divided into the intervention group and the regular group according to the difference of management procedures during the perioperative period. ERAS was carried out in 57 patients in the intervention group, while conventional management procedures were applied in 57 patients in the regular group. Thereafter, compared were the fluctuations in nutritional indicators and immunological indicators, postoperative complications, time to recovery of gastrointestinal function, length of stay (LOS) in hospital and cost of patients between the two groups. RESULTS: Seven days post-operation in the intervention group, the evaluation indexes of nutrition status, including total protein (TP), albumin (ALB), prealbumin (PA) and transferrin (TF), and of immunological functions, including immunoglobulin G (IgG), immunoglobulin A (IgA), immunoglobulin M (IgM) and total blood lymphocyte count (TLC), were significantly higher than those in the regular group. As for postoperative complications, the incidence rate of the intervention group was remarkably lower than that of the regular group; the recovery time of gastrointestinal function in the intervention group was shorter than that in the regular group; the LOS in the intervention group was also shorter than that in the regular group; the in-hospital cost in the intervention group was also lower than that in the regular group. All differences above were statistically significant (p<0.05). CONCLUSION: During the perioperative period of esophageal carcinoma patients, ERAS should be fully applied to sustain the good status, and promote the recovery of immunological functions and gastrointestinal functions; at the same time, ERAS also reduces the incidence rate of postoperative complications, LOS and in-hospital cost, and we maintain that ERAS should be performed in clinical practice.

AXL is a marker for epithelial-mesenchymal transition in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common cancer in China and certain other parts of the world with a dismal prognosis for affected patients. AXL is a member of the TYRO3-AXL-MER family of receptor tyrosine kinases, and has been revealed to be an important mediator of epithelial-mesenchymal transition (EMT) in several types of cancer. However, to the best of our knowledge, its function in EMT in ESCC cells has not yet been examined. The present study employed two independent ESCC mRNA profile datasets and revealed that AXL is associated with several EMT markers. Gene Set Enrichment Analysis indicated that EMT occurs more in ESCC with high AXL expression. Analysis on another dataset demonstrated further that increased expression of AXL in ESCC is associated with increased migratory ability. Collectively, the results of the present study provide evidence that AXL is a marker for EMT in ESCC.

RasGRP3, a Ras guanyl releasing protein 3 that contributes to malignant proliferation and aggressiveness in human esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide; however, clinical and pathological parameters have limited ability in discriminating between clinically significant and indolent ESCC. Since RasGRP3 transcript levels have prognostic value in discriminating ESCC with different clinical aggressiveness, we decided to investigate its putative oncogenic role in ESCC. We found that RasGRP3 was highly expressed in ESCC cells. Suppression of endogenous RasGRP3 expression in esophageal cell lines reduced Ras-GTP formation as well as AKT phosphorylation. RasGRP3 suppression also inhibited cell invasion and migration and reduced proliferation, demonstrating the importance of RasGRP3 for the transformed phenotype of melanoma cells. Suppression of RasGRP3 expression in these cells inhibited downstream RasGRP3 responses and suppressed cell growth and migration, confirming the functional role of RasGRP3 in the altered behaviour of these cells. This suggests that RasGRP3 may function as a Ras activator in the phosphoinositide signalling pathway and may potentially serve as a new therapeutic target.

A comparative study on the efficacy of fast-track surgery in the treatment of esophageal cancer patients combined with metabolic syndrome.

The purpose of our study was to evaluate the clinical efficacy of fast-track surgery (FTS) in the treatment of esophageal cancer patients combined with metabolic syndrome. Ninety-four esophageal cancer patients with metabolic syndrome were selected in Affiliated Hospital of Jining Medical University from March, 2016 to February, 2017. Patients were randomly divided into control group and observation group with 47 cases in each group. Patients in observation group were treated with FTS, while patients in control group were treated with traditional method. Intraoperative blood loss, the number of dissected lymph nodes, operation time, postoperative hospital stay, the cost of hospitalization, postoperative readmission rate, and incidence of postoperative complications were compared between the groups. Levels of serum inflammatory cytokines (TNF-α and hs-CRP), fat cell factor chemerin and leptin (LP) were detected by enzyme-linked immunosorbent assay (ELISA) at 1 month after surgery. Levels of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) at 1 month after surgery were compared between groups. Levels of hemoglobin (Hb), albumin (Alb), prealbumin (PAB) and transferrin (TRF) at 1 month after surgery were also compared between the two groups. Treatment of cancer quality-of-life questionnaire-esophageal cancer (OES-18) module was used to evaluate the symptoms of patients at one month after surgery. It turned out that no significant differences in intraoperative blood loss, operation time and the number of dissected lymph nodes were found between groups (p>0.05). Postoperative hospital stay, the cost of hospitalization, postoperative readmission rate and the incidence of postoperative complications were significantly lower in observation group than in control group (p<0.05). Levels of TNF-α, hs-CRP, chemerin and LP in observation group were significantly lower than those in control group at one month after surgery (p<0.05). Levels of TC, TG and LDL-C were significantly lower and HDL-C level was significantly higher in observation group than in control group at one month after surgery (p<0.05). Levels of Hb and Alb were significantly lower and levels of PAB and TRF were significantly higher in observation group than in control group at one month after surgery (p<0.05). OES-18 score of observation group was significantly better than that of control group at one month after surgery (p<0.05). As a conclusion, FTS can promote postoperative rehabilitation, shorten hospital stay, reduce economic burden and reduce the rehospitalization rate of esophageal cancer patients. At the same time, FTS can also improve the lipid metabolism, nutritional status and regulate the differentiation of adipocytes, alleviate the low inflammatory response state, which in turn promotes metabolic syndrome.

Pemetrexed plus dendritic cells as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer who had treatment with TKI.

The aim of this study was to determine the efficacy and toxicity of pemetrexed plus dendritic cells (DCs) in patients suffering from stage IIIB or IV lung adenocarcinoma, who had undergone maintenance treatment with gefitinib or erlotinib. Patients who had failed gefitinib or erlotinib maintenance treatment had ECOG performance statuses ranging from 0 to 2.27 patients received pemetrexed plus DCs as second-line treatment. Dosage: 500 mg/m(2) pemetrexed was administered on day 1 of a 21-day cycle. DCs were given for one cycle of 21 days. Three patients (11.1 %) experienced a partial response and 14 patients (51.9 %) showed stable disease. Ten patients (37.0 %) had progressive disease. The median time to progression-free survival (PFS) was 4.8 months [95 % confidence interval (CI) 4.4-5.2], and the median overall survival was 10.7 months (95 % CI 10.3-11.2). In the subgroup analysis, PFS had a significant difference between the low ratio of CD4/CD8 and normal ratio of CD4/CD8, with 4.5 months (95 % CI 4.2-4.9) and 5.0 months (95 % CI 4.5-5.7), (Log Rank = 0.039), respectively. No one patient experienced grade 4 toxicity. A regimen of pemetrexed combined with DCs is marginally effective and well tolerated in patients with stage IIIB or IV lung adenocarcinoma who had received gefitinib or erlotinib first-line treatment.

Treatment of stage IIIb/IV non-small cell lung cancer with Pemetrexed plus Oxaliplatin after failure of Erlotinib as second-line treatment.

To determine the efficacy and toxicity of Pemetrexed plus Oxaliplatin in patients suffering from stage IIIb or IV lung adenocarcinoma and being treated with Erlotinib as second-line treatment, a total of 45 patients were randomly divided into two groups. One group was treated with 500 mg/m(2) Pemetrexed plus 100 mg/m(2) Oxaliplatin, and the other was treated with 500 mg/m(2) Pemetrexed plus 75 mg/m(2) Cisplatin. All drugs were administered on day one of a 21-day cycle. In the Oxaliplatin group, 3 patients (13.6 %) experienced partial response (PR), 9 patients (41.0 %) showed stable disease (SD), and 10 patients (45.5 %) had progressive disease (PD). In the Cisplatin group, 2 patients (8.7 %) experienced PR, 7 patients (30.4 %) showed SD, and 14 patients (60.9 %) had PD. The PFS of the Oxaliplatin group and the Cisplatin group was 4.45 months (95 % CI 4.10-4.80) and 3.96 months (95 % CI 3.68-4.24) (P = 0.03), respectively. The median overall survival (OS) was 10.8 months (95 % CI 10.2-11.5) and 10.7 months (95 % CI 10.2-11.3) (P = 0.72), respectively. There was no statistically significant difference in the occurrence rate of grades 3 and 4 myelotoxicity between the two groups. However, there was a significant difference in the occurrence rate of grades 3 and 4 gastrointestinal reactions and peripheral neurotoxicity between the two groups (P < 0.05). A regime combining Pemetrexed and Oxaliplatin was marginally effective and well tolerated in patients with stage IIIb or IV lung adenocarcinoma who have received Erlotinib as second-line treatment.