N6-methyladenosine Reader YTHDF1-induced lncRNA DLGAP1-AS2 Promotes the c-Myc Mediated Gastric Cancer Aerobic Glycolysis

Background: Emerging data has demonstrated the essential function of N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) in human tumorigenesis. Nevertheless, the regulation of m6A-lncRNA approach on gastric cancer (GC) tumorigenesis is unclear. Methods: LncRNA expression profile data was derived from GEO. M6A profile was screened using Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). The metabolism assays were conducted using quantitative analysis of glucose, lactate, ATP and extracellular acidification rate (ECAR). The m6A level of specific RNA was identified using MeRIP-qPCR. The molecular interaction was detected using RIP assay.Results: In the findings, results showed that enhanced DLGAP1-AS2 expression was correlated with advanced pathological stage and poor prognosis. Functionally, DLGAP1-AS2 promoted the aerobic glycolysis and knockdown of DLGAP1-AS2 suppressed the tumor growth of GC cells. Mechanistically, m6A reader YTHDF1 accelerated the enrichment of DLGAP1-AS2 in GC. Moreover, DLGAP1-AS2 interacted with YTHDF1 to integrate c-Myc mRNA, thereby enhancing the stability of c-Myc mRNA through DLGAP1-AS2/m6A/YTHDF1/c-Myc mRNA. Conclusions: In conclusion, our work indicates a novel m6A-maintained lncRNA DLGAP1-AS2 in the GC aerobic glycolysis, disclosing a m6A-reader-dependent modality regulation.

CUL4B Promotes Temozolomide Resistance in Gliomas by Epigenetically Repressing CDNK1A Transcription

Resistance to temozolomide (TMZ), the first-line chemotherapeutic drug for glioblastoma (GBM) and anaplastic gliomas, is one of the most significant obstacles in clinical treatment. TMZ resistance is regulated by complex genetic and epigenetic networks. Understanding the mechanisms of TMZ resistance can help to identify novel drug targets and more effective therapies. CUL4B has been shown to be upregulated and promotes progression and chemoresistance in several cancer types. However, its regulatory effect and mechanisms on TMZ resistance have not been elucidated. The aim of this study was to decipher the role and mechanism of CUL4B in TMZ resistance. Western blot and public datasets analysis showed that CUL4B was upregulated in glioma specimens. CUL4B elevation positively correlated with advanced pathological stage, tumor recurrence, malignant molecular subtype and poor survival in glioma patients receiving TMZ treatment. CUL4B expression was correlated with TMZ resistance in GBM cell lines. Knocking down CUL4B restored TMZ sensitivity, while upregulation of CUL4B promoted TMZ resistance in GBM cells. By employing senescence β-galactosidase staining, quantitative reverse transcription PCR and Chromatin immunoprecipitation experiments, we found that CUL4B coordinated histone deacetylase (HDAC) to co-occupy the CDKN1A promoter and epigenetically silenced CDKN1A transcription, leading to attenuation of TMZ-induced senescence and rendering the GBM cells TMZ resistance. Collectively, our findings identify a novel mechanism by which GBM cells develop resistance to TMZ and suggest that CUL4B inhibition may be beneficial for overcoming resistance.

Circulating stromal cells in resectable pancreatic cancer correlates to pathological stage and predicts for poor clinical outcomes

Pancreatic cancer (PC) is notoriously difficult to diagnosis and properly stage resulting in incorrect primary treatment. Diagnostic and prognostic biomarkers are desperately needed to more accurately stage patients and select proper treatments. Recently, a newly discovered circulating stromal cell, i.e. cancer associated macrophage-like cell (CAML), was found to accurately identify solid cancers and predict for worse prognosis. In this pilot study, blood samples were procured from 63 PC patients prior to start of therapeutic intent. CAMLs were found in 95% of samples tested, with ≥12 CAMLs/7.5 mL and ≥50 µm CAMLs both predicting for advanced pathological stage and progression free survival. These data suggest that CAML assessment prior to treatment of PC predicts patients with under-staged disease and with more aggressive PC less likely to respond to standard of care treatment.

Factors associated with failure of bony union after conservative treatment of acute cases of unilateral lumbar spondylolysis

Background: If bone union is expected, conservative treatment is generally selected for lumbar spondylolysis. However, sometimes conservative treatments are unsuccessful. We sought to determine the factors associated with failure of bony union in acute unilateral lumbar spondylolysis with bone marrow edema including contralateral pseudoarthrosis.Methods: This study targeted unilateral lumbar spondylolysis treated conservatively in high school or younger students. Conservative therapy was continued until the bone marrow edema disappeared on MRI and bone union was investigated by CT. We conducted a univariate analysis of sex, age, pathological stage, lesion level complicating the contralateral bone defect, lesion level, and intercurrent spina bifida occulta, and variables with p < 0.1 were considered in a logistic regression analysis. An item with p < 0.05 was defined as a factor associated with failure of bony union.Results: We found 92 cases of unilateral spondylolysis with bone marrow edema and 66 cases were successfully treated conservatively. Failure of bony union in unilateral lumbar spondylolysis with bone marrow edema was associated with advanced pathological stage (p = 0.004), contralateral pseudoarthrosis (p < 0.001), and L5 lesion level (p = 0.002). The odds ratio was 20.0 (95% CI 3.0–193.9) for advanced pathological stage, 78.8 (95% CI 13–846) for contralateral pseudoarthrosis, and 175 (95% CI 8.5–8192) for L5 lesion level.Conclusions: Conservative therapy aiming at bony union is contraindicated in cases of acute unilateral spondylolysis when the pathological stage is advanced, the lesion level is L5, or there is contralateral pseudoarthrotic spondylolysis.

Factors associated with failure of bony union after conservative treatment of acute cases of unilateral lumbar spondylolysis

Background: If bone union is expected, conservative treatment is generally selected for lumbar spondylolysis. However, sometimes conservative treatments are unsuccessful. We sought to determine the factors associated with failure of bony union in acute unilateral lumbar spondylolysis with bone marrow edema including contralateral pseudoarthrosis.Methods: This study targeted unilateral lumbar spondylolysis treated conservatively in high school or younger students. Conservative therapy was continued until the bone marrow edema disappeared on MRI and bone union was investigated by CT. We conducted a univariate analysis of sex, age, pathological stage, lesion level complicating the contralateral bone defect, lesion level, and intercurrent spina bifida occulta, and variables with p < 0.1 were considered in a logistic regression analysis. An item with p < 0.05 was defined as a factor associated with failure of bony union.Results: We found 92 cases of unilateral spondylolysis with bone marrow edema and 66 cases were successfully treated conservatively. Failure of bony union in unilateral lumbar spondylolysis with bone marrow edema was associated with advanced pathological stage (p = 0.004), contralateral pseudoarthrosis (p < 0.001), and L5 lesion level (p = 0.002). The odds ratio was 20.0 (95% CI 3.0–193.9) for advanced pathological stage, 78.8 (95% CI 13–846) for contralateral pseudoarthrosis, and 175 (95% CI 8.5–8192) for L5 lesion level.Conclusions: Conservative therapy aiming at bony union is contraindicated in cases of acute unilateral spondylolysis when the pathological stage is advanced, the lesion level is L5, or there is contralateral pseudoarthrotic spondylolysis.

Factors Associated with Failure of Bony Union After Conservative Treatment of Acute Cases of Unilateral Lumbar Spondylolysis

Background: If bone union is expected, conservative treatment is generally selected for lumbar spondylolysis. However, sometimes conservative treatments are unsuccessful. We sought to determine the factors associated with failure of bony union in acute unilateral lumbar spondylolysis with bone marrow edema including contralateral pseudoarthrosis.Methods: This study targeted unilateral lumbar spondylolysis treated conservatively in high school or younger students. Conservative therapy was continued until the bone marrow edema disappeared on MRI and bone union was investigated by CT. We conducted a univariate analysis of sex, age, pathological stage, lesion level complicating the contralateral bone defect, lesion level, and intercurrent spina bifida occulta, and variables with p < 0.1 were considered in a logistic regression analysis. An item with p < 0.05 was defined as a factor associated with failure of bony union.Results: We found 92 cases of unilateral spondylolysis with bone marrow edema and 66 cases were successfully treated conservatively. Failure of bony union in unilateral lumbar spondylolysis with bone marrow edema was associated with advanced pathological stage (p = 0.004), contralateral pseudoarthrosis (p < 0.001), and L5 lesion level (p = 0.002). The odds ratio was 20.0 (95% CI 3.0–193.9) for advanced pathological stage, 78.8 (95% CI 13–846) for contralateral pseudoarthrosis, and 175 (95% CI 8.5–8192) for L5 lesion level.Conclusions: Conservative therapy aiming at bony union is contraindicated in cases of acute unilateral spondylolysis when the pathological stage is advanced, the lesion level is L5, or there is contralateral pseudoarthrotic spondylolysis.

Surgical Outcomes and Risk Analysis of Primary Pulmonary Sarcoma

Background Primary pulmonary sarcoma (PPS) is a rare malignant lung neoplasm, and there is very little medical evidence about treatment of PPS. The aim of this study is to clarify the clinical characteristics and therapeutic outcome of patients who underwent surgical resection for PPS. Methods We retrospectively reviewed the records of patients who underwent surgical resection for PPS in our institution between 1995 and 2014. Cases who only underwent biopsy were excluded. Results A total of 24 patients (18 males, 6 females), with a median age of 60 (interquartile range: 44–67) years, were analyzed. The surgical procedures performed in these patients were pneumonectomy (n = 10), lobectomy (n = 11), and wedge resection (n = 3). Complete resection was achieved in 16 patients. The pathological stages (tumor, node, metastases lung cancer classification, 8th edition) of the patients were I (n = 4), II (n = 12), III (n = 2), and IV (n = 5), and there were four cases of lymph node metastasis. The 5-year overall survival rate of the patients was 50% (95% confidence interval [CI]: 29–72). Adverse prognostic factors for overall survival were incomplete resection (hazard ratio [HR]: 4.4, 95% CI: 2.1–42), advanced pathological stage (HR 14, 95% CI: 2.8–66), higher pathological grade (HR 4.5, 95% CI: 1.2–17), and tumor size ≥ 7 cm (HR 4.7, 95% CI: 1.1–21). Conclusions Our series of PPS revealed that incomplete resection, advanced pathological stage, higher pathological grade, and tumor size were unfavorable factors for long-term survival.

PS02.238: POSTOPERATIVE PROGNOSTIC NUTRITIONAL INDEX CAN PREDICT A LONG-TERM PROGNOSIS OF ESOPHAGEAL CANCER

Background Recent reports indicate the nutritional and immune status often affect the long-term prognosis of patients with cancer. The preoperative prognostic nutritional index(PNI) is used as an evaluation of the perioperative nutritional status, and it is reported that the PNI level correlates with postoperative results. However, only a handful of reports have discussed the predictive prognostic potential of postoperative PNI. The aim of this study is to clarify the correlation of postoperative PNI level and long-term prognosis of patients with esophagus cancer who underwent esophagectomy. Methods A total of 29 patients with esophageal cancer who received neoadjuvant chemotherapy followed by radical esophagectomy from January 2011 to December 2014 were retrospectively reviewed. The calculation of PNI level is as follows: 10 × serum albumin level (g/dL) + 0.005 × total lymphocyte count (/mm3). The postoperative PNI level was measured three months after radical esophagectomy. The patients were stratified by postoperative PNI level by two groups using calculated cutoff level (PNI = 43.9) by receiver operating characteristic curve. The correlation of 3-year disease-free survival (DFS) and postoperative PNI level was evaluated. Results Of the total, 25 were male and 4 were female. The median age of patients was 68 years (31–79 years). Overall, patients received 1–2 cycles of preoperative chemotherapy with 5-FU and cisplatin. Of these 29 patients, 9 (31.0%) responded to chemotherapy (8 patients had a partial response and 1 had a complete response). The median postoperative PNI level was 47.2 (38.0–58.9). Univariate analyses showed that 3-year DFS was worse in patients with low postoperative PNI level (P = 0.017), advanced pathological stage (P = 0.029) and younger age (< 70 years) (P = 0.02). Multivariate analyses showed that low postoperative PNI level[hazard ratio (HR) 0.224, 95% confidence interval (CI) 0.060–0.83, P = 0.026] and advanced pathological stage (HR 3.197, 95% CI 1.13–9.06, P = 0.029) were independent predictors of 3-year DFS. Conclusion Our findings suggest that the postoperative PNI level may be a useful marker to predict a prognosis of patients with esophagus cancer. Nutrition intervention for undernourished patients after surgery may improve prognosis of patients with esophagus cancer. Disclosure All authors have declared no conflicts of interest.