Background: Cancer-associated fibroblasts (CAFs), as the activated stroma cells, contribute to tumor progression via the release of cytokines, growth factors, and hormones. However, neither the factors produced by CAFs nor the molecular mechanisms were illuminated very well in gastric cancer (GC).Methods: Immunohistochemical staining of alpha-smooth muscle actin (α-SMA) was applied to examine the number of CAFs in GC samples from 227 patients. ELISA and qRT-PCR were performed to detect the expression of interleukin 17a (IL-17a). The migration and invasion of GC cells were determined by the Transwell assay. The expressions of JAK2, STAT3, MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured by western blotting. IL-17a was blocked with a polyclonal antibody, and JAK2/STAT3 signaling pathway was blocked by a specific inhibitor AG490.Results: High CAFs in GC tissues were positively correlated with advanced TNM stage and perineural invasion. Furthermore, GC patients with high CAFs in tumor tissues had an obvious worse disease-free survival (DFS) and disease-special survival (DSS). Multivariate analysis showed that high CAFs in GC tissues were an independent risk factor for DFS and DSS. CAFs expressed IL-17a significantly after GC cell co-culture. CAFs markedly enhanced the migration and invasion abilities of AGS and SGC-7901 cells.Moreover, CAFs co-culture resulted in increased levels of MMP2/9, reduced expressions of TIMP1/2, and activation of the JAK2/STAT3 signaling pathway in the GC cells. IL-17a neutralizing antibody or JAK2 inhibitor AG490 can significantly inhibit the effects of CAFs on the migration, invasion, MMP2/9, TIMP1/2, and JAK2/STAT3 pathways of GC cells.Conclusions: CAFs correlated with unfavorable clinical features and poor prognosis of GC patients. CAFs secreted IL-17a, which promoted the migration and invasion of GC cells through activating JAK2/STAT3 signaling. These results may identify IL-17a as a promising prognostic marker and therapeutic target of GC.

Analysis of circulating miRNAs (cmiRNAs) before surgical operation (BSO) and after the surgical operation (ASO) has been informative for lung adenocarcinoma (LUAD) diagnosis, progression, and outcomes of treatment. Thus, we performed a biological network analysis to identify the potential target genes (PTGs) of the overexpressed cmiRNA signatures from LUAD samples that had undergone surgical therapy. Differential expression (DE) analysis of microarray datasets, including cmiRNAs (GSE137140) and cmRNAs (GSE69732), was conducted using the Limma package. cmiR-1246 was predicted as a significantly upregulated cmiRNA of LUAD samples BSO and ASO. Then, 9802 miR-1246 target genes (TGs) were predicted using 12 TG prediction platforms (MiRWalk, miRDB, and TargetScan). Briefly, 425 highly expressed overlapping miRNA-1246 TGs were observed between the prediction platform and the cmiRNA dataset. ClueGO predicted cell projection morphogenesis, chemosensory behavior, and glycosaminoglycan binding, and the PI3K–Akt signaling pathways were enriched metabolic interactions regulating miRNA-1245 overlapping TGs in LUAD. Using 425 overlapping miR-1246 TGs, a protein–protein interaction network was constructed. Then, 12 PTGs of three different Walktrap modules were identified; among them, ubiquitin-conjugating enzyme E2C (UBE2C), troponin T1(TNNT1), T-cell receptor alpha locus interacting protein (TRAIP), and ubiquitin c-terminal hydrolase L1(UCHL1) were positively correlated with miR-1246, and the high expression of these genes was associated with better overall survival of LUAD. We conclude that PTGs of cmiRNA-1246 and key pathways, namely, ubiquitin-mediated proteolysis, glycosaminoglycan binding, the DNA metabolic process, and the PI3K–Akt–mTOR signaling pathway, the neurotrophin and cardiomyopathy signaling pathway, and the MAPK signaling pathway provide new insights on a noninvasive prognostic biomarker for LUAD.

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Purpose This study aimed to explore the feasibility and safety of the tunnel approach in laparoscopic radical right hemicolectomy for colon cancer. Methods From July 2016 to October 2018, a total of 106 consecutive patients with colon cancer who underwent laparoscopic radical right hemicolectomy at the Affiliated Cancer Hospital of Zhengzhou University were enrolled. The patients were stratified into either a tunnel approach (TA) (n = 56) group or traditional medial approach (MA) (n = 50) group according to the surgical technique performed. The baseline demographics, perioperative outcomes and oncologic outcomes were compared between the two groups. Results The baseline characteristics did not differ between groups. The TA group had significantly less blood loss [20.0 (10.0–40.0) vs. 100 (100.0–150.0) ml, p < 0.001] and a shorter operation time [128.4 ± 16.7 vs. 145.6 ± 20.3 min, p < 0.001] than the MA group. The time to first flatus and postoperative hospital stay were similar [3.0 (2.0–4.0) vs. 3.0 (3–4.0) days, p = 0.329; 10.4 ± 2.6 vs. 10.7 ± 3.0 days, p = 0.506] between the two groups. The conversion to laparotomy and complication rates were similar between groups (0 vs. 6.0%, p = 0.203; 14.3% vs. 18.0%, p = 0.603, respectively). No treatment-related deaths occurred in either group. The TA group did not have significantly better survival outcomes than the MA group (p = 0.372). Conclusions The TA seems to allow for more favourable results in terms of blood loss and operative time than the MA, with similar results regarding time to first flatus, hospital stay, postoperative complication rate, conversion rate and oncologic outcomes; moreover, the TA is easier for beginners to master.

e16549 Background: Neoadjuvant chemotherapy for patients with locally advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC) can improve the overall survival without increasing operation risk. Nowadays, immunotherapy has become a new promising neoadjuvant treatment. Therefore, we intended to evaluate the safety and efficacy of camrelizumab (anti-PD-1 antibody) combined with FOLFOX as the neoadjuvant therapy for patients with locally advanced GC/GEJC who received D2 radical gastrectomy. Methods: Patients who were diagnosed as resectable locally advanced GC/GEJC received the neoadjuvant treatment of camrelizumab and FOLFOX every 2 weeks for 4 cycles. Imaging evaluation was performed in 2-4 weeks after neoadjuvant therapy. Patients who had no progression disease (PD) were recruited. Eligible patients underwent gastrectomy with D2 lymph node dissection through laparotomy or laparoscopic surgery. The primary end points were safety and R0 resection rate. Results: From July 24 2019 to January 31 2020, 15 patients were recruited. The mean age was 57 years. A total of 10(67%) were males and 5(33%) were females. According to AJCC 8th, cT3 and cT4 were confirmed in 7(47%) patients and 8(53%) patients, N1 and N2 in 7(47%) patients and 8(53%) patients, respectively. During operation, intraperitoneal metastases were found in 2 patients. Of the 13 surgeries, only 2 were laparoscopic and the others were laparotomy. The surgical procedures included Roux-en-Y (9, 69.2%), Billroth II (1, 7.7%) and jejunum interposition (3, 23.1%). Thirteen patients underwent gastrectomy with D2 lymph node dissection and all of them were confirmed R0 resection by postoperative pathology results. The mean lymph node yield was 44.1±13.2 nodes, positive lymph node yield was 1.8±2.8 nodes. Duration time of surgery was 186.5±45.5 minutes, mean blood loss was 219.2±109 ml during the operation. Mean hospital stays were 13.2±2.4 days. Only 1 patient experienced grade 3 pneumonia. Neither serious intraoperative complications nor immune-related adverse events both prior and post operation were observed. There was no treatment-related death. Conclusions: Camrelizumab combined with FLOFOX as neoadjuvant treatment for patients with locally advanced GC/GEJC showed acceptable toxicity and promising efficacy with low complications and mortality. Clinical trial information: NCT03939962 .