Background: Routine clinical surveillance involves serial radiographic imaging following radical surgery in localized non-small cell lung cancer (NSCLC). However, such surveillance can detect only macroscopic disease recurrence and is frequently inconclusive. We investigated if detection of ctDNA before and after resection of NSCLC identifies the patients with risk of relapse, and furthermore, informs about response to management. Methods: We recruited a total of 77 NSCLC patients. A high-throughput 127 targetgene capture technology and a high-sensitivity circulating single-molecule amplification and resequencing technology (cSMART) assay were used to detect the somatic mutations in the tumor tissues as well as the plasma of NSCLC patients before and after surgery to monitor for minimal residual disease (MRD). Kaplan-Meier and Cox regression analysis were performed to evaluate the relapse-free survival (RFS) and overall survival (OS) of patients with predictor variables. Results: Patients with a higher stage (III/IV) and preoperative ctDNA-positive status demonstrated a significant 2.8-3.4-fold risk and 3.8-4.0-fold risk for recurrence and death, respectively. Preoperative ctDNA-positive patients associated with a lower RFS (HR = 3.812, p = 0.0005) and OS (HR = 5.004, p = 0.0009). Postoperative ctDNApositive patients also associated with a lower RFS (HR = 3.076, p = 0.0015) and OS (HR = 3.195, p = 0.0053). Disease recurrence occurred among 63.3% (19/30) of postoperative ctDNA-positive patients. Most of these patients 89.5% (17/19) had detectable ctDNA within 2 weeks after surgery and was identified in advance of radiographic findings by a median of 12.6 months. Conclusion: Advanced stage and preoperative ctDNA-positive are strong predictors of RFS and OS in localized NSCLC patients undergoing complete resection. Postoperative detection of ctDNA increases chance to detect early relapse, thus can fulfill an important role in stratifying patients for immediate further treatment with adjuvant and neoadjuvant therapy.

Background: VATS is currently the most popular form of access for lung cancer resection in the UK. However, there is limited comparative information from high quality randomised controlled trials and no information on early oncologic outcomes for quality assurance for a minimal access approach. VIOLET is the largest randomised trial conducted to date to compare clinical efficacy, safety and oncologic outcomes of VATS versus open surgery for lung cancer. Method: VIOLET is a parallel group randomised trial conducted across 9 UK thoracic surgery centres. Participants with known or suspected primary lung cancer were randomised in a 1:1 ratio to VATS (one to four ports) or open lobectomy. Randomisation was stratified by surgeon. Patients within clinical stage cT1-3, N0-1 and M0 using TNM 8 with disease suitable for VATS or open surgery were eligible to join the trial. We report on early outcomes in the period from randomisation to hospital discharge after surgery. Result: From Jul 2015 to Feb 2019, 2,109 patients were screened to randomise 503 participants to VATS (n¼247) or open (n¼256) lobectomy. The mean age (SD) was 69 (8.8) years and 249 (49.5%) were male. Baseline clinical T category was cT1 333 (67.3%), cT2 125 (25.2%), cT3 37 (7.5%) with cN0 466 (94%) and cN1 30 (6%). Lobectomy was undertaken in 221 (89.5%) patients randomised to VATS and 232 (90.6%) patients randomised to open surgery. The in-hospital mortality rate was 1.4% (7/502) and the conversion rate from VATS to open was 5.7% (14/246) with the main reasons listed as pleural adhesions (n¼4) and bleeding (n¼4). There were no differences in R0 resection; which was 98.8% ( 218/223) in the VATS group and 97.4% (228/234) in the open group; P¼0.839 or in nodal upstaging from cN0/1 to pN2 disease which was observed in 6.2% (15/244) of the VATS group and 4.8% (12/252) of the open group; P¼0.503. The median (visual analogue) pain score was 4 (interquartile range, IQR 2 to 5) in both groups on day one with 3 (1 to 5) in the VATS group and 4 (2 to 5) in the open group on day two. A significant reduction of overall in-hospital complications was observed in patients receiving VATS at 32.8% (81/247) compared to open 44.3% (113/255) surgery; P¼0.008 without any difference in serious adverse events between the two groups, which was 8.1% (20/247) for VATS and 7.8% (20/255) for open surgery; P¼0.897. Patients randomised to VATS had a shorter median (IQR) length of stay of 4 (3 to 7) versus 5 (3 to 8) days compared to patients randomised to open surgery, P¼0.008. Conclusion:In early stage lung cancer, VATS lobectomy is associated with significantly lower in-hospital complications and shorter length of stay compared to open lobectomy. This was achieved without any compromise to early oncologic outcomes (pathologic complete resection and upstaging of mediastinal lymph nodes) nor any difference in serious adverse events in the early post-operative period.

Dp71 is one of the most ubiquitously expressed isoforms of dystrophin, the pathological genes of DMD. In order to find whether the alteration of Dp71 can affect the phenotypes of cell other than PC12, an A549 cell line with stably transfected Dp71 siRNA plasmids was set up and named A549-Dp71AS cell. It is demonstrated for the first time that the A549-Dp71AS cell line displayed decreased invasion capabilities, reduced migration ability, decreased proliferation rate, and lessened clonogenic formation. Cisplatin-induced apoptosis was also increased in A549-Dp71AS cell line via enhancing the Caspase 3, Caspase 8, and Caspase 9 activities. Knocking down Dp71 expression can significantly inhibit the A549 xenograft tumor growth in nude mice. The A549-Dp71AS cells and xenograft tumor tissues displayed reduced lamin B1, Bcl-2, and MMP2 protein expression, which accounts for the reduced malignancy of A549-Dp71AS cells in vivo and in vitro.

For the first time, dramatically decreased Dp71 protein and mRNA was found in 34 pairs of resected primary gastric adenocarcinoma. Immunohistochemistry identified Dp71 expression suppressed in 72.2% of 104 gastric cancer patients. The decreased Dp71 expression was significantly correlated with cancer differentiation (P=0.001) and lymph vascular invasion (p=0.041). Decreased Dp71 expression was associated with a poor gastric adenocarcinoma prognosis (P=0.001). Significantly less Dp71 mRNA and protein were found in BGC823, SGC7901, AGS compared with GES-1. Via increasing lamin B1 mRNA and protein, enforced Dp71d and Dp71f expression resulted in SGC7901 proliferation inhibition. Co-IP proved interaction of Dp71 with lamin B1 in GES-1 cells. Further expression characterization showed reduced lamin B1 in gastric cancer tissue and cancer cells. Increasing lamin B1 expression results in the growth inhibition of SGC7901, which suggests that Dp71-lamin B1 protein complex plays an important role for the newly identified tumor suppressive function of Dp71.