The RNA-binding protein RBM47 inhibits non-small cell lung carcinoma metastasis through modulation of AXIN1 mRNA stability and Wnt/ß-catentin signaling.

BACKGROUND: Non-small-cell lung cancer (NSCLC) remains a highly prevalent and deadly form of cancer, with efforts to better understand the molecular basis of the progression of this disease being essential to its effective treatment. Several recent studies have highlighted the ability of RNA-binding proteins (RBPs) to regulate a wide range of cellular processes in both healthy and pathogenic contexts. Among these RBPs, RNA binding motif protein 47 (RBM47) has recently been identified as a tumor suppressor in both breast and colon cancers, whereas its role in NSCLC is poorly understood. METHODS: RBM47 expression in NSCLC samples was evaluated by RT-PCR, western blotting and immunohistochemistry analysis. Molecular and cellular techniques including lentiviral vector-mediated knockdown were used to elucidate the functions and mechanisms of RBM47. RESULTS: This study sought to analyze the expression and role of RBM47 in NSCLC. In the present study, we observed reduced levels of RBM47 expression in NSCLC, with these reductions corresponding to a poorer prognosis and more advanced disease including a higher TNM stage (p = 0.022), a higher likelihood of tumor thrombus (p = 0.001), and pleural invasion (p = 0.033). Through functional analyses in vitro and in vivo, we further demonstrated that these RBP was able to disrupt the proliferation, migration, and invasion of NSCLC cells. At a molecular level, we determined that RBM47 was able to bind the AXIN1 mRNA, stabilizing it and thereby enhancing the consequent suppression of Wnt/ß-catentin signaling. CONCLUSION: Together our findings reveal that RBM47 targets AXIN1 in order to disrupt Wnt/ß-catenin signaling in NSCLC and thereby disrupting tumor progression. These results thus offer new insights into the molecular biology of NSCLC, and suggest that RBM47 may also have value as a prognostic biomarker and/or therapeutic target in NSCLC patients.

A NOVEL PROGNOSTIC INDEX IN PATIENTS WITH RESECTABLE ESOPHAGEAL SQUAMOUS CELL CARCINOMA: FIBRINOGEN/PREALBUMIN RATIO.

BACKGROUND: Fibrinogen (Fib) to albumin (ALB) fibrinogen-to-albumin ratio as a prognostic index for esophageal cancer has been confirmed. A novel prognostic index was initially proposed with fibrinogen to prealbumin ratio (FPR) in patients with resectable esophageal squamous cell carcinoma (ESCC). OBJECTIVE: The objective of the study was to study the prognostic role of the novel prognostic index (FPR) in patients with resectable ESCC without any neoadjuvant treatment. METHODS: In this retrospective study, a total of 372 resectable ESCC patients without any neoadjuvant treatment were included. The best cutoff values were selected by the receiver operating characteristic curves. Two Cox regression analyses with forward stepwise (one for categorical variables and the other for continuous variables) were used to evaluate the overall survival (OS) and cancer-specific survival (CSS). RESULTS: The best cutoff point was 0.014 for FPR. Patients with lower levels of FPR (≤0.014) had better CSS (50.7% vs. 18.0%, p < 0.001) and OS (48.0% vs. 17.6%, p < 0.001) than patients with higher levels of FPR (> 0.014). Multivariate Cox analyses (categorical and continuous) demonstrated that FPR was an independent prognostic factor in CSS (categorical: hazard ratio [HR]: 2.014, 95% confidence interval [CI]: 1.504-2.697, p < 0.001; continuous per 0.01: HR: 1.438, 95% CI: 1.154-1.793, p = 0.001) and OS (categorical: HR: 1.964, 95% CI: 1.475-2.617, p < 0.001; continuous per 0.01: HR: 1.429, 95% CI: 1.146-1.781, p = 0.002). CONCLUSIONS: Our study indicated that FPR served as an independent prognostic factor in patients with resectable ESCC.

A novel prognostic index in patients with resectable esophageal squamous cell carcinoma: fibrinogen/prealbumin ratio

ABSTRACT Background: Fibrinogen (Fib) to albumin (ALB) fibrinogen-to-albumin ratio as a prognostic index for esophageal cancer has been confirmed. A novel prognostic index was initially proposed with fibrinogen to prealbumin ratio (FPR) in patients with resectable esophageal squamous cell carcinoma (ESCC). Objective: The objective of the study was to study the prognostic role of the novel prognostic index (FPR) in patients with resectable ESCC without any neoadjuvant treatment. Methods: In this retrospective study, a total of 372 resectable ESCC patients without any neoadjuvant treatment were included. The best cutoff values were selected by the receiver operating characteristic curves. Two Cox regression analyses with forward stepwise (one for categorical variables and the other for continuous variables) were used to evaluate the overall survival (OS) and cancer-specific survival (CSS). Results: The best cutoff point was 0.014 for FPR. Patients with lower levels of FPR (≤0.014) had better CSS (50.7% vs. 18.0%, p < 0.001) and OS (48.0% vs. 17.6%, p < 0.001) than patients with higher levels of FPR (> 0.014). Multivariate Cox analyses (categorical and continuous) demonstrated that FPR was an independent prognostic factor in CSS (categorical: hazard ratio [HR]: 2.014, 95% confidence interval [CI]: 1.504-2.697, p < 0.001; continuous per 0.01: HR: 1.438, 95% CI: 1.154-1.793, p = 0.001) and OS (categorical: HR: 1.964, 95% CI: 1.475-2.617, p < 0.001; continuous per 0.01: HR: 1.429, 95% CI: 1.146-1.781, p = 0.002). Conclusions: Our study indicated that FPR served as an independent prognostic factor in patients with resectable ESCC.

Final report of a prospective randomized study on thoracic radiotherapy target volume for limited-stage small cell lung cancer with radiation dosimetric analyses.

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

Expression and clinical significance of p75NTR in esophageal squamous cell carcinoma.

Objectives: To analyze the expression and clinical significance of p75NTR in esophageal squamous cell carcinoma. Methods: Sixty patients with esophageal squamous cell carcinoma who underwent surgical resection in our hospital between January 2017 and January 2018 were selected as the study subjects. The content of the study was in accordance with medical ethics and approved by the medical ethics committee, and patients understood and signed an informed consent form. The clinical data of all patients were analyzed retrospectively. The positive rate of p75NTR in lymph node metastasis-positive patients, lymph node metastasis-negative patients and patients with invasion of the muscle layer was detected and statistically analyzed. Results: Lymph node metastasis-positive patients had a p75NTR-positive rate of 100.00% (30/30), which was significantly higher than that of lymph node metastasis-negative patients (20.00% (6/30)) (P < 0.05) The p75NTR-positive rate in patients with infiltration of the muscular layer was 73.33% (20/30), which was significantly higher than that of patients with infiltration of the whole layer (43.33% (13/30) (P < 0.05). Conclusions: The high expression of p75NTR in esophageal squamous cell carcinoma tissue can indicate the invasion depth of the cancerous tissue and lymph node metastasis, and the clinical introduction of the p75NTR index can be the basis for an effective prognosis prediction in patients with esophageal squamous cell carcinoma.

Prognostic value of lactate dehydrogenase to albumin ratio (LAR) in patients with resectable esophageal squamous cell carcinoma.

BACKGROUND: We firstly identified a combination of lactate dehydrogenase (LDH) along with albumin (ALB), which was defined as LAR (LDH/ALB ratio). The purpose of our study here was initially to explore the prognostic role of LAR in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophagectomy. PATIENTS AND METHODS: A retrospective study was conducted including 346 resectable ESCC patients. Patients who received curative surgery without any neoadjuvant therapy were included in the current study. The X-tile program was performed to calculate the optimal cut-off values for LDH, ALB and LAR. The Kaplan-Meier methods, Cox regression univariate and multivariate analyses were utilized to analyze the prognostic factors for cancer-specific survival (CSS). RESULTS: There were 76 (22.0%) women and 270 (78.0%) men in all 346 patients. The mean value for serum LDH, ALB and LAR were 180±62 U/L (range 28-473 U/L), 40.3±5.3 g/L (range 26.6-52.4 g/L) and 4.6±1.8 (range 0.64-14.97), respectively. According to the X-tile program, the optimum cut-off points were 220 (U/L), 40.5 (g/L), and 5.5 for LDH, ALB, and LAR, respectively. The 5-year CSS was 31.8%. Patients with a high level of LAR (>5.5) were associated with poor CSS (13.3% vs 38.3%, P<0.001). Multivariate analyses revealed that LAR was an independent predictor in resectable ESCC patients (P=0.038). CONCLUSION: Our retrospective observations indicate that LAR is a useful potential prognostic biomarker in resectable ESCC patients who received curative surgery without any neoadjuvant therapy with the optimal cut-off value of 5.5.

C-Reactive Protein to Prealbumin Ratio (CPR): A Novel Inflammatory-Nutritional Prognostic Factor for Predicting Cancer-Specific Survival (CSS) and Overall Survival (OS) in Patients with Resectable Esophageal Squamous Cell Carcinoma.

BACKGROUND: The inflammation and nutrition play an important role in prognosis. A novel index combined with inflammatory and nutritional biomarkers, named C-reactive protein (CRP) to prealbumin (PALB) ratio (CPR), was initially reported to predict the prognosis in resectable esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: A retrospective study was conducted including 346 resectable ESCC patients. The X-tile program was used to confirm the optimal cut-off value. The Kaplan-Meier methods and Cox regression analyses were performed to analyze the cancer-specific survival (CSS) and overall survival (OS). RESULTS: The optimum cut-off point was 0.03 for CPR. Patients with a high level of CPR (> 0.03) were associated with poor CSS (12.0% vs. 43.0%, P<0.001) and OS (11.2% vs. 40.7%, P<0.001). Multivariate analyses revealed that CPR was an independent predictor in resectable ESCC patients (CSS, P=0.008; OS, P=0.007). CONCLUSION: This study, to the best of our knowledge, is the first to investigate prognostic role of CPR in patients with ESCC. Our retrospective observations indicate that CPR, with the optimal cut-off value of 0.03, is a useful potential predictor in resectable ESCC patients.

The impact of functional LIG4 polymorphism on platinum-based chemotherapy response and survival in non-small cell lung cancer.

DNA repair capacity is correlated with the sensitivity of cancer cells toward platinum-based chemotherapy. The aim of this study was to investigate whether single-nucleotide polymorphisms (SNPs) in DNA repair genes NBS1, LIG4, and RAD51 were correlated with tumor response in advanced non-small cell lung cancer (NSCLC) patients in a Chinese population who received platinum-based chemotherapy. The treatment outcomes of 146 advanced NSCLC patients who were treated with platinum-based chemotherapy were evaluated. The polymorphic status of three SNPs was determined by genotyping via the polymerase chain reaction-restriction fragment length polymorphism method. Forty-five patients in the group with the CC genotype (45/90) showed a good response to treatment, while only 18 patients in the CT+TT group (18/55) showed a good response, indicating a substantial differences in the chemotherapy response rate based on the LIG4 Thr9Ile polymorphism (P = 0.042). Patients with the GG genotype for the NSB1 Glu185Gln polymorphism were more sensitive to platinum-based chemotherapy compared with patients with either the CG or CC genotype (P = 0.001). Kaplan-Meier analysis of all patients showed a significant association between the LIG4 Thr9Ile CC polymorphism and superior progression-free survival and overall survival (log-rank P = 0.045 and 0.031, respectively). However, there were no significant differences in survival based on the LIG4 Thr9Ile or the RAD51 135G>C polymorphisms. Polymorphisms in the NSB1 and LIG4 genes may be a predictive marker for treatment response and for advanced NSCLC patients in stage IIIB + IV. The CC genotype of the LIG4 Thr9Ile polymorphism may also serve as an independent prognosis factor.

MicroRNA-17, microRNA-18a, and microRNA-19a are prognostic indicators in esophageal squamous cell carcinoma.

BACKGROUND: The members of the microRNA (miR)-17-92 cluster have been reported to be highly expressed in several cancers. However, whether their expression is associated with clinicopathologic factors, the prognosis of patients in esophageal squamous cell carcinoma (ESCC) remains unknown. METHODS: Using SYBR green real-time quantitative reverse transcription polymerase chain reaction, we detected the expression of members of the miR-17-92 cluster, including miR-17, miR-18a, miR-19a, miR-20a, miR-19b, and miR-92a, in 105 surgical specimens from ESCC patients. We then investigated their impact on clinicopathologic factors and survival. RESULTS: All six members of the miR-17-92 cluster had a significantly higher level of expression in the 105 ESCC tissue specimens than in normal esophageal mucosa (p < 0.05). The miR-18a expression positively correlated with tumor stage (p = 0.025). Meanwhile, miR-92a expression positively correlated with clinical stage (p = 0.022), and miR-19b expression positively correlated with tumor size (p = 0.005), lymph node metastasis (p = 0.040), and clinical stage (p = 0.011). The overexpression of miR-17a was correlated positively with lymph node metastasis (p = 0.035) and clinical stage (p = 0.022). MiR-18a, miR-17, and miR-19a were prognostic indicators for progression-free survival and overall survival. both in univariate analysis and in multivariate analysis. CONCLUSIONS: This study suggests that miR-17, miR-18a, and miR-19a can serve as potential unfavorable prognostic biomarkers in ESCC which are associated with some clinicopathologic factors. However, the regulatory pathway associated with potential candidate miRNAs remains to be explored.

[Evaluation of molluscicidal effects of contracted responsibility system in Changshan County].

OBJECTIVE: To explore a new molluscicidal pattern suitable for the complicated environments in hilly regions, so as to provide the evidence for making the strategy of Oncomelania snail control. METHODS: The contracted responsibility system for snail control was implemented by government. The quality of control work was evaluated in the same year and the recent molluscicidal effect was assessed in the next spring. RESULTS: After the intervention, the decline rate of snail areas increased from 53.4% to 100%; the compression rate of snail spots increased from 54.6% to 100%; the input of fund for snail control decreased from 2.03 Yuan/m2 to 0.69 Yuan/m2; the cost of snail control decreased from 3.73 Yuan/m2 to 0.75 Yuan/m2; the work efficiency increased from 12.0 m2/(man x day) to 36.7 m2/(man x day); the molluscicide decreased from 7.50 tons/year to 3.20 tons/year and the decline rate was 57.3%. The awareness rate and recognized rate of the contracted responsibility system for snail control were both 92.5%. CONCLUSION: The contracted responsibility system for snail control can increase financing efficiency, molluscicidal quality and work efficiency, and save molluscicide in complicated environments of hilly regions.

The prognostic significance of p63 and Ki-67 expression in myoepithelial carcinoma.

BACKGROUND: Myoepithelial carcinoma is a rare tumour. The clinical and biological behaviours of these tumours are variable. Although many factors have been evaluated as potential prognostic indicators, including clinical stage, site and size of the tumour, high proliferative activity, extensive invasion into the surrounding tissue, perineural permeation, the abnormal presence of nuclear DNA content, and marked cellular pleomorphism, there are no definite histological features that clearly correlate with their behaviour. Thus, conclusions regarding prognostic factors and ideal treatment may emerge as the number of investigated myoepithelial carcinoma cases accumulate. METHODS: Using immunohistochemistry, expression levels of p63 and Ki-67 were determined in 16 myoepithelial carcinoma samples and correlated with clinicopathological characteristics and patient prognosis. RESULTS: p63 expression was detected in six of the myoepithelial carcinoma tissues (37.5%) and Ki-67 was detected in five (31.3%). In addition, p63 and Ki-67 expression levels were associated with myoepithelial carcinoma recurrence and metastasis. All six patients with p63-positive expression died due to disease or cardiovascular disease (mean survival time = 50.5 months), and p63 expression was statistically significant with respect to survival (P = 0.01). Four patients with Ki-67-positive expression died due to disease or cardiovascular disease (mean survival time = 44.0 months); however, there was no statistically significant difference between Ki-67 expression and survival (P = 0.24). CONCLUSIONS: Recurrence and metastasis in myoepithelial carcinomas are more frequent in p63-positive and Ki-67-positive EMCs, and poor prognosis is associated with overexpression of p63.

[Analysis of prognostic factors in patients with locoregional recurrence of esophageal carcinoma after curative treatment].

OBJECTIVE: The aim of this paper was to evaluate the treatment outcome of multimodal treatment for 196 patients with locoregional recurrent esophageal cancer after curative treatment and to determine the prognostic factors of recurrence. METHODS: One hundred and ninety six patients with locoregional recurrent esophageal cancer curatively treated in our hospital were included in this study. Kaplan-Meier method was used to analyze the survival rate. Log rank test was used to evaluate the difference between the groups. Multivariate survival analysis was conducted using a Cox proportional hazard regression model with a backward stepwise procedure. RESULTS: The overall 1-, 2- and 3-year survival rates were 29.8%, 5.9% and 4.0%, respectively, with a median survival time of 8.0 months. The univariate analysis showed that ECOG PS, the interval between initial treatment and recurrence, the regimens of initial treatment and retreatment were independent prognostic factors. The multivariate analysis showed that the regimens of initial treatment and retreatment were independent prognostic factors. Retreatment methods significantly influenced the survival. The median survival time of chemoradiotherapy, radiation therapy alone, chemotherapy alone, EGFR-TKI and best supportive care were 13.0, 7.0, 6.0, 4.0 and 3.0 months, respectively (P = 0.000). CONCLUSIONS: The prognosis of patients with locoregional recurrent esophageal cancer after curative treatment is poor. The main prognostic factors are the regimens of initial treatment and retreatment. Multimodal treatment including radiotherapy and chemotherapy may improve the long-term survival of the patients.

[Related factors of right recurrent nerve nodal involvement in esophageal cancer].

OBJECTIVE: To study the related factors of right recurrent nerve nodal involvement in esophageal cancer. METHODS: 280 patients with thoracic esophageal cancer received esophagectomy and right recurrent nerve node dissection. The clinicopathological data were analyzed retrospectively. Univariate data were analyzed by chi-square test, and multivariate data were analyzed by logistic regression. RESULTS: The right recurrent nerve nodal metastasis was found in 76 cases (27.1%, 76/280). In the 979 excised right recurrent nerve nodes, metastases were found in 118 nodes (12.1%). The tumor staging, the total number of involved lymph nodes, vascular invasion, the number of lymph node metastases in the thorax, the number of lymph node metastasis in the abdomen, subcarinal node metastasis, and peri-esophageal lymph node metastasis were independent risk factors of right recurrent nerve node metastasis in esophageal carcinoma. CONCLUSION: Right recurrent nerve lymph nodes should be dissected in those patients with high risk factors of lymph node metastasis in thoracic esophageal carcinoma.

Gastric adenomyoma presenting as melena: a case report and literature review.

Gastric adenomyoma (AM) is a rare benign tumor characterized by gland-like structures embedded within a smooth muscle stroma. We report a case of a 68-year-old man with gastric AM admitted to our hospital for melana. Endoscopic examination revealed a gastric mass of about 4 cm in diameter, located in the antrum. Histologic examination of the excised specimen showed irregularly arranged glands and interlacing smooth muscle bundles surrounding the glandular elements. Although gastric AM is rare, it should be considered in differential diagnosis of extramucosal gastric tumor.

Comparison of the clinical and immunohistochemical features, including anaplastic lymphoma kinase (ALK) and p53, in inflammatory myofibroblastic tumours.

This retrospective study evaluated 15 cases of inflammatory myofibroblastic tumours (IMTs) to determine histological atypicality, clinicopathological features, outcomes, and expression of anaplastic lymphoma kinase-1 (ALK1) and p53, to assess potential pathological prognostic indicators. Nine patients with complete follow-up had no evidence of recurrence, including two with recurrent disease who were treated with additional surgery. Six patients had local recurrence and distant metastasis. Six (40.0%) tumours showed cellular atypicality. Significant correlations were found between histological atypicality and recurrence and metastasis. Recurrence was documented in 25.0% of ALK-positive and 63.6% ALK-negative IMTs, whereas metastasis was confined to the ALK-negative group. Recurrence and metastasis were documented in 50.0% and 25.0% of p53-positive IMTs, respectively, and in 57.1% and 57.1%, respectively, of the p53-negative IMTs. The IMT cases had high recurrence and metastasis and there were significant correlations between histological atypicality and recurrence and metastases, and between absence of ALK reactivity and recurrence. No correlation was found between p53 expression and any clinicopathological feature of IMT.

[Sleeve resection for lung cancer: a report of 82 cases].

BACKGROUND & OBJECTIVE: Bronchial sleeve resection and/or pulmovascular sleeve resection can maximize preservation of normal lung tissues after tumor resection, which provides a resection mode for lung cancer surgery. This study was to investigate the technique, operative results and survival of lung cancer patients after sleeve resection. METHODS: Eighty-two central lung cancer patients underwent sleeve resection in Zhejiang Cancer Hospital from Jun. 2001 to Dec. 2006. Among them, 23 underwent concomitant pulmovascular sleeve resection, 2 underwent pulmovascular sleeve resection alone. All patients received systematic lymph node dissection. The results of lymph node dissection and the occurrence of postoperative complications were studied. The survival of patients was analyzed by Kaplan-Meier method. RESULTS: An average of 20 lymph nodes (range, 9-57; median, 19 ) were dissected from 82 patients. Of the 82 patients, 49 (59.8%) were at stage N1, 21 (25.6%) at stage N2. Two (2.4%) patients died 2 and 3 days after operation. No bronchial anastomotic leakage occurred. The 1-, 2-, 3-, and 5-year survival rates were 78.4%, 52.5%, 39.1%, and 23.4%, respectively, with a median survival of 26 months. There were no significant differences in 1-, 3-, and 5-year survival rates between male and female patients, or between the patients aged of <60 and > or =60. The differences in 1-, 3-, and 5-year survival rates among N1(-) N2(-), N1 (+) N2(-), N2(+) patients, and among stageI, II, IIIA, IIIB patients were significant (P<0.01). CONCLUSIONS: Perioperative mortality and the incidence of anastomosis-related complications for lung cancer patients after sleeve resection are low. Sleeve resection is an alternative to pneumonectomy for certain indications. Systematic lymph node dissection does not increase operative complications and mortality. The survival of lung cancer patients after sleeve resection is conelated to lymph node metastasis and clinical stage, but has no correlation to gender or age.