Baofu Chen

Translesion synthesis (TLS) polymerases enable cells to bypass or overcome DNA damage during DNA replication and contributes to genomic instability and cancer. Inhibition of the expression of TLS genes enhances the sensitivity of cancer cells to cisplatin. This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) in the TLS genes and clinical outcome of advanced non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. A total of 16 SNPs were genotyped and analyzed in 302 advanced NSCLC patients (discovery set), and the results were further validated in additional 428 NSCLC patients (validation set). Analyses revealed significant associations of two SNPs, rs3213801 and rs3792136, with overall survival, with the lowest combined P values of 0.003 and 0.016, respectively. These effects also remained in stratification analyses by clinical variables. Furthermore, the number of risk genotypes of the two SNPs showed a cumulative effect on overall survival (P = 0.03). Genetic polymorphisms in the TLS genes might serve as potential predictive biomarkers of prognosis of advanced NSCLC patients treated with platinum-based chemotherapy.

Germline mutations in FLCN are responsible for ~10% of patients with primary spontaneous pneumothorax (PSP), characterized by multiple lung cysts in the middle/lower lobes and recurrent pneumothorax. These clinical features are also observed in a substantial portion of patients with sporadic PSP exhibiting no FLCN coding mutations. To assess the potential underlying mechanisms, 71 patients with PSP were selected, including 69 sporadic and 2 familial cases, who bared FLCN mutation‑like lung cysts, however, harbored no FLCN protein‑altering mutations. Notably, in a significant proportion of the patients, FLCN irregulation was observed at the transcript and protein levels. Genetic analyses of the cis‑regulatory region of FLCN were performed by sequencing and multiplex ligation‑dependent probe amplification assay. No inheritable DNA defect was detected, with the exception of a heterozygous deletion spanning the FLCN promoter, which was identified in a family with PSP. This mutation caused a reduction in the expression of FLCN in the lung cysts. Pedigree analysis demonstrated that haploinsufficiency of FLCN was pathogenic. To determine whether epigenetic mechanisms may be involved in the irregulation of FLCN, the promoter methylation status was measured in the remainder of the patients. No evidence of FLCN promoter methylation was demonstrated. The present study suggested that FLCN irregulation in lung cysts of PSP is not associated with promoter methylation.

Background and Objectives: CCAT2, a novel long non‐coding RNAs (lncRNAs), is found to promote the metastasis and invasion of colon, lung, and breast cancers. This study aimed to investigate the level of CCAT2 in esophageal squamous cell carcinoma (ESCC) and to elucidate its clinical significance.Methods: The expression level of CCAT2 and the status of MYC amplification were examined in 229 ESCC samples using quantitative real‐ time PCR.Results: CCAT2 was upregulated in ESCC tissues, especially in cases with lymph node metastasis (LNM), advanced TNM stages, and MYC amplification. Furthermore, the level of CCAT2 was positively correlated with TNM stages, LNM, and the number of positive lymph nodes. High CCAT2 expression and MYC amplification were significantly associated with TNM stages and LNM. Survival analyses revealed that high CCAT2 expression and MYC amplification were significantly associated with poorer overall survival in ESCC patients. Furthermore, patients with high CCAT2 expression and MYC amplification had a 2.199‐fold increased risk of death compared with those with low CCAT2 expression and MYC non‐amplification.Conclusions: Our study provides the first evidence associating CCAT2 expression and poor survival in ESCC. CCAT2 may be a prognostic biomarker and therapeutic target for ESCC. J. Surg. Oncol. 2015 111:834–839.

To investigate the relationship between (GT)n polymorphism and esophageal cancer by analyzing the connection between microsatellite polymorphisms in the promoter of heme oxygenase-1 and the clinicopathological characteristics of esophageal squamous cell carcinoma (ESCC) in Han chinese population. The (GT)n repeats in HO-1 gene in 83 male and 43 female hospital-based patients with ESCC (aged between 40 and 79 years with a mean of (61 ± 8) years) and 134 healthy control individuals were obtained by DNA sequencing. Polymorphisms of the (GT)n repeats were generally grouped into three classes based on allele frequencies: class S alleles (<25 repeats), class M alleles (25 to 29 repeats), and class L alleles (≥30 repeats). The correlation between susceptibility and clinicopathological characteristics of ESCC were analyzed by χ2 test. For in vitro experiments, the transient-transfection assay was performed to explore the correlation between different lengths of (GT)n repeats and promoter activity by assessing the promoter activities of HO-1 gene in cultured Ecal09 cells treated with H2O2 by analysis of cariance. Higher frequencies of L-allele (25. 8% vs. 14. 9%, χ2 = 9. 520, P = 0. 002), L-allele carrier (41. 3% vs. 27. 6%, χ2 = 5. 381 , P = 0. 020) were found in patients with ESCC. Furthermore, the lymphatic metastasis rate (63. 5% vs. 41. 8%, χ = 5. 685, P = 0. 017) and the detection rate of poorly differentiated ESCC cell (53. 8% vs. 28. 4%, χ2 = 8. 335, P = 0. 004) was significantly higher in L-allele carriers compared to non-L-allele carriers. In transfection experiments, promoter activities of 5'-flanking regions of the HO-1 gene in Eca109 cells transfected with the recombinant gene carrying (GT)16 repeat after treatment with H2O2 increased (F = 23. 615,P = 0. 008). In H2O treated control group, compared to (GT)26 and (GT)36, the basal promoter activities of HO-1 gene carrying (GT)16 repeat increased (F =41. 376, P = 0. 003; F = 50. 761, P = 0. 002). The long (GT)n repeats of HO-1 gene promoter can increase the susceptibility of esophageal squamous cell carcinoma and the risk of lymphatic metastasis.

To investigate the effect and mechanism of recombinant human erythropoietin (rhEPO) on angiogenesis in chronic ischemic porcine myocardium. A ameroid constrictor was placed around the proximal circumflex branch of the left coronary artery in 12 Bama miniatures' swine artery by thoracoscopy. Electrocardiogram and coronary angiography were used to confirm the establishment of myocardial ischemia. The animals were divided into rhEPO treatment group (n = 6) and negative control group (n = 6). Treatment group received subcutaneous injection of rhEPO at 1, 3, 7, 14, 21 days, control group received saline. The expression of vascular endothelial growth factor (VEGF) in serum was assessed by ELISA. Ultrasonography and coronary angiography were assessed 28 days after therapy. Western blot was used to detect the expression of VEGF, phosphorylated protein kinase B (p-Akt) and phosphorylated extracellular signal regulated kinases (p-Erk). The degree of angiogenesis was assessed by immunohistochemical analysis. Serum VEGF rose significantly in both control and treatment groups, peaking at 3 days and then returning to the near-baseline level at 28 days, but the two groups showed no significant difference at each time point (P > 0.05). Echocardiographic measurements showed that the left ventricular systolic function of animals in treatment group increase significantly after rhEPO therapy. the expression levels of VEGF, p-Akt and p-Erk had markedly increased, which resulted in a 2.5-fold increased of VEGF, 1.1-fold increased of p-Akt, 1.5-fold increased of p-Erk (t = 37.721, 10.907, 12.957, all P = 0.000). there were significant increase in capillary density and arteriole density in the two groups ((944 ± 98) %/mm² vs. (569 ± 102) %/mm², (73 ± 13) %/mm² vs. (45 ± 10) %/mm², t = 4.214, 2.869, P = 0.016, 0.023). rhEPO can promote angiogenesis and arteriogenesis and improve the left ventricular systolic function in porcine model of chronic myocardial ischemia. The potential mechanism is to up-regulated the expression of p-Akt and p-Erk.

To investigate the feasibility and efficacy of neoadjuvant chemoradiotherapy followed by combined thoracoscopic and laparoscopic esophagectomy (CTLE) in the treatment of advanced esophageal carcinoma. From June 2011 to February 2012, 11 patients with locally advanced esophageal carcinoma underwent neoadjuvant chemoradiotherapy followed by CTLE (clinical stage IIB-IIIA). NP (vinorelbine pin and cisplatin) or TP (program paclitaxel-pin and cisplatin) were applied as preoperative chemotherapy. During the same period, conventional fractionated radiotherapy was used with the radiation dose of 40 Gy/20 F. At four to six weeks after CRT, 11 patients received three-incision CTLE. During chemoradiation, 9 patients developed bone marrow suppression. The interval between completion of chemoradiation and surgery was (49.6±15.4) d. Intraoperative findings revealed local fibrosis in one patient (75 days after chemoradiation) while operative difficulty was not increased in the remaining 10 patients. Compared to 15 patients who received surgery alone, operative time was shorter [(242.3±27.0) min vs.(280.5±27.2) min, P=0.002] and intraoperative blood loss was less [(168.2±95.6) ml vs. (244.5±84.8) ml, P=0.042], the number of removal lymph nodes was similar [(19.5±5.8) vs. (20.5±7.1), P=0.683], postoperative hospital stay was prolonged [(18.9±10.3) d vs. (12.5±4.6) d, P=0.020]. The postoperative complication rate was 36.4% including cervical anastomotic leak with pulmonary infection (n=1), cervical anastomotic fistula and hoarseness (n=1), pulmonary infection with pleural effusion (n=2). Follow up ranged from 1 to 9 months, and no recurrence was found. The neoadjuvant chemoradiotherapy followed by combined thoracoscopic and laparoscopic esophagectomy in the treatment of locally advanced esophageal carcinoma is safe, feasible, and the short-term outcomes are favorable.

Chromosome 8q24 is commonly amplified in many types of cancer, particularly lung cancer. Polymorphisms in this region are associated with risk of different cancers. To investigate the relationship between three single nucleotide polymorphisms (SNPs) (rs1447295, rs16901979 and rs6983267) on 8q24 and lung cancer risk, we conducted an association study in two Han Chinese populations: one population was from Zhejiang Province (576 case patients and 576 control subjects), whereas the other was from Fujian Province (576 case patients and 576 control subjects). We found that rs6983267 was significantly associated with an increased risk of lung cancer in both populations. Compared with the TT genotype, the GG genotype was associated with a significant 1.555-fold increased risk of lung cancer [95% confidence interval (CI) 1.218–1.986, P = 4.0×10⁻⁴]. This effect was more pronounced in never-smokers [odds ratio (OR) = 2.366, 95% CI 1.605–3.488, P = 1.4×10⁻⁵]. Analyses stratified by histology revealed that rs6983267 GG genotype was most associated with patients with other histological types (OR = 3.012, 95% CI 1.675–5.417, P = 2.3×10⁻⁴). The AA genotype of rs1447295 was associated with increased risk for adenocarcinoma compared with the CC genotype (OR = 2.260, 95% CI 1.174–4.353, P = 0.015). Furthermore, the GG genotype of rs6983267 was associated with worse survival in the Zhejiang population (hazard ratio (HR) = 1.646, 95% CI 1.099–2.464, P = 0.016). No association was observed for rs16901979. These results suggest that genetic variations on 8q24 may play significant roles in the development and progression of lung cancer.

To investigate the influence of combined thoracoscopic and laparoscopic esophagectomy for early postoperative pulmonary function, and to study the relative factors for postoperative pulmonary complications. From September 2009 to December 2010, 61 patients with esophageal cancer had undergone esophagectomy surgery, of which 32 patients had undergone combined thoracoscopic and laparoscopic esophagectomy (CTLE group), and 29 patients had undergone open three-field esophagectomy (open group). Pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV(1)) were measured on the 1(th) preoperative day, 5(th) and 10(th) postoperative day, and arterial blood gas analyses were performed during the same period. Meanwhile, pain scores and other potentially relevant factors were recorded as well. Preoperative pulmonary function and arterial blood gas analysis, including FEV(1)%, FVC%, PaO2 in two groups had no significant difference (t = -1.608 to 0.709, P = 0.113 to 0.481). On the 10(th) postoperative day, FEV(1)%, FVC%, PaO2, and SaO2 of two groups were significantly different (FEV(1)%: 77% ± 17% vs. 53% ± 13%, t = 6.241, P = 0.000; FVC%: 78% ± 13% vs. 57% ± 16%, t = 5.549, P = 0.000; PaO2: (87 ± 9) mmHg vs. (79 ± 14) mmHg, t = 2.477, P = 0.017; SaO2: 96% ± 3% vs. 94% ± 2%, t = 2.313, P = 0.024; 1 mmHg = 0.133 kPa). Pain score of CTLE group was lower than open group, and the scores of two groups had significant difference before the 5(th) day after surgery (t = -4.398 to -1.815, P = 0.000 to 0.049). Postoperative pulmonary complications of CTLE group was lower than open group (6/32 vs. 12/29, χ(2) = 3.745, P = 0.049). Combined thoracoscopic and laparoscopic esophagectomy has advantages on early postoperative pulmonary function. It can relatively reduce the incidence of pulmonary complications after surgery.

To explore and evaluate the feasibility, safety, radicality and the short-term outcome of minimally invasive esophagectomy versus open esophagectomy for esophageal cancer. From July 2007 to October 2009, 67 patients with esophageal cancer received minimally invasive esophagectomy (MIE group), while 38 patients underwent conventional open esophagectomy (OE group: via right thorax, abdomen, left neck). The operative procedures, clinicopathological data and short-term outcome were collected and compared between the two groups. The clinical data of the two groups were comparable. No significant differences was found in demographics between the two groups. Median blood loss in MIE group was less than that in OE group (chest: 112.3 ml vs. 175.3 ml, P = 0.035, abdominal: 31.4 ml vs. 100.5 ml, P = 0.026). More patients in OE group were transferred to ICU (P = 0.042) and more obvious pain (P = 0.005). The rate of pulmonary infection and intestinal obstruction in OE group were higher than MIE group (P = 0.046 and 0.045). There were no differences in the number of lymph node dissection for two groups, the average was 20.9 and lymph node metastasis rate was 26.9% in MIE group. Mean follow up was (14.0 ± 2.2) months (range, 2 to 29 months). Recurrence rate and survival rate were no differences. The Minimally invasive esophagectomy for esophageal cancer is feasible, safe, and reliable short-term effect, and can achieve radical tumor resection, which may lead to better future of surgical treatment for esophageal carcinoma.