Background: Esophageal squamous cell carcinoma (ESCC) is a common invasive malignancy worldwide with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been reported to be involved in cancer development. However, lncRNAs that are functional in ESCC and the underlying molecular mechanisms remain largely unknown. Methods: Transcriptomic analysis was performed to identify dysregulated lncRNAs in ESCC tissue samples. The high expression of LINC00680 in ESCC was validated by RT-qPCR, and the oncogenic functions of LINC00680 was investigated by cell proliferation, colony formation, migration and invasion assays in ESCC cells in vitro and xenografts derived from ESCC cells in mice. RNA-seq, competitive endogenous RNA (ceRNA) network analysis, and luciferase reporter assays were carried out to identify LINC00680 target genes and the microRNAs (miRNAs) bound to LINC00680. Antisense oligonucleotides (ASOs) were used for in vivo treatment. Results: Transcriptome profiling revealed that a large number of lncRNAs was dysregulated in ESCC tissues. Notably, LINC00680 was highly expressed, and upregulation of LINC00680 was associated with large tumor size, advanced tumor stage, and poor prognosis. Functionally, knockdown of LINC00680 restrained ESCC cell proliferation, colony formation, migration, and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, LINC00680 was found to act as a ceRNA by sponging miR-423-5p to regulate PAK6 (p21-activated kinase 6) expression in ESCC cells. The cell viability and motility inhibition induced by LINC00680 knockdown was significantly reversed upon PAK6 restoration and miR-423-5p inhibition. Furthermore, ASO targeting LINC00680 substantially suppressed ESCC both in vitro and in vivo. Conclusions: An oncogenic lncRNA, LINC00680, was identified in ESCC, which functions as a ceRNA by sponging miR-423-5p to promote PAK6 expression and ESCC. LINC00680/miR-423-5p/PAK6 axis may serve as promising diagnostic and prognostic biomarkers and therapeutic targets for ESCC.

Background: Exosomes have emerged as critical mediators of intercellular communication. Hypoxia is widely recognized as a key regulator of tumor aggressiveness, and significantly affects exosome release by tumor cells. However, the effects of exosomes derived from hypoxic lung adenocarcinoma (LUAD) cells are poorly understood. Methods: Samples of miRNA isolated from hypoxic LUAD cell-derived exosomes (HExo) and normoxic LUAD cell-derived exosomes (NExo) were sequenced to identify miRNAs that might mediate tumor progression. Exosomal miRNA was co-cultured with LUAD cells to assess its biological effects on cell migration and metastasis both in vitro and in vivo. The cellular target of exosomal miRNA was confirmed by dual-luciferase assays. Western blot studies showed that exosomal miRNA regulated the related pathway. The availability of circulating exosomal miRNA derived from plasma was also evaluated. Results: We found that HExo could significantly enhance the migration and invasion of normoxic LUAD cells. MiRNA sequencing results suggested that miR-31-5p was largely internalized within HExo and could be taken up by normoxic LUAD cells. Exosomal miR-31-5p was found to directly target Special AT-Rich Sequence-Binding Protein 2 (SATB2)-revered epithelial mesenchymal transition and significantly increase activation of MEK/ERK signaling, thereby contributing to tumor progression both in vitro and in vivo. Furthermore, higher levels of circulating exosomal miR-31-5p were detected in LUAD patients, especially in patients with metastatic disease. Conclusions: Our findings demonstrate that exosomal miR-31-5p exerts a crucial role in LUAD progression, and could serve as a diagnostic biomarker for LUAD.

Preliminary results of single-port versus triple-port complete thoracoscopic lobectomy for non-small cell lung cancer

Uniportal video-assisted thoracoscopic surgery (UniVATS) has been widely adopted in China, where several ultra-high volume thoracic surgical and training centers are located. The objective of this consensus from Chinese experts was to summarize the current application and give reference for the future development of UniVATS in the treatment of lung cancer. A panel of 41 experts from 21 Chinese hospitals was invited to join this project. The Delphi method was used in this consensus consisting of two rounds of voting. The questionnaire was based on the current clinical evidence. Forty (97.6%) experts completed the 2 rounds of questionnaires. The experts’ experience was relatively similar. We defined the UniVATS as monitor-dependent surgery, no use of rib-spreading and single incision less than 4 cm. Tumor with stage of T1–T3 and N0–N2 is considered amenable to UniVATS. Other consensus was reached on several points outlining the safety and feasibility, surgical skills, learning curve, short-term and long-term outcomes for lung cancer, and current application of subxiphoid and nonintubated UniVATS approach. This consensus statement represents a collective agreement among Chinese experts to suggest that UniVATS is an effective alternative to multi-portal approach, although high-level evidence is expected in the future. Some agreements can be referred in the training of young surgeons.

Neoadjuvant chemoradiation is not recommended as an approach for treatment of esophageal squamous cell carcinoma due to its significant postoperative mortality. However, it is assumed the combination of neoadjuvant chemoradiation with minimally invasive esophagectomy (MIE) may reduce postoperative mortality, which can revive preoperative chemoradiation. No randomized controlled studies comparing neoadjuvant chemoradiation plus MIE with neoadjuvant chemotherapy plus MIE have been performed so far. The present trial is initiated to obtain valid information whether neoadjuvant chemoradiation plus MIE yields better survival without worse postoperative morbidity and mortality in the treatment of locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0). CMISG1701 is a multicenter, prospective, randomized, phase III clinical trial, investigating the safety and efficacy of neoadjuvant chemoradiation plus MIE compared with neoadjuvant chemotherapy plus MIE. Patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) are eligible for the study. A total of 264 patients are randomly assigned to neoadjuvant chemoradiation (arm A) or neoadjuvant chemotherapy (arm B) with a 1:1 allocation ratio. The primary outcome is overall survival assessed with a minimum follow-up of 36 months. Secondary outcomes are progression-free survival, recurrence-free survival, postoperative pathologic stage, treatment-related complications, postoperative mortality as well as quality of life. The objective of this trial is to identify the superior protocol with regard to patient survival, treatment morbidity/mortality and quality of life between neoadjuvant chemoradiation plus MIE and neoadjuvant chemotherapy plus MIE. NCT03001596 (December 17, 2016).

Background: This study’s objective was to evaluate and summarize the application of the IQQA-3D imaging interpretation and analysis system in uniportal video-assisted thoracoscopic anatomical segmentectomy. Methods: We collected the clinical data of consecutive patients who underwent uniportal video-assisted thoracoscopic anatomical segmentectomy for single or multiple pulmonary nodules at Department No. 1 of Thoracic Surgery at Fujian Medical University, Fujian Union Hospital from July 2017 to November 2018. Patients were divided into two groups according to the use of IQQA: the IQQA group and non-IQQA group. General clinical characteristics, operation status, and postoperative recovery were compared between groups. Variations in the segmental bronchi, arteries, and veins of patients in the IQQA group were summarized. Results: This study included 133 cases, 96 in the IQQA group and 37 in the non-IQQA group. There were no significant differences between groups in patient sex, age, preoperative smoking, pulmonary function, maximum lesion diameter, or pathological type (all P>0.05). The proportion of segmentectomies that were moderately difficult or complex was significantly higher in the IQQA group than in the non-IQQA group (28.1% vs. 16.2% and 29.2% vs. 13.5%, respectively; P=0.017). Despite having a higher percentage of more complicated operations, the IQQA group did not have longer operation times or increased postoperative complications. Fifty-five cases (57.3%) in the IQQA group had segmental structure variations, with a total of 73 variations. Among patients who underwent IQQA, 27 (65.9%) in the general segmentectomy group, 13 (48.1%) in the moderate segmentectomy group, and 15 (53.6%) in the complex segmentectomy group had anatomic variations; these differences were not significant. Conclusions: Preoperative 3D reconstruction is necessary before segmentectomy, especially for patients undergoing moderate or complex segmentectomy. IQQA was safe and feasible for preoperative localization of lesions, surgical planning, and intraoperative navigation in uniportal video-assisted thoracoscopic anatomical segmentectomy and can facilitate complicated segmentectomy.