Immunosuppressive molecules are extremely valuable prognostic biomarkers across different cancer types. However, the diversity of different immunosuppressive molecules makes it very difficult to ...accurately predict clinical outcomes based only on a single immunosuppressive molecule. Here, we establish a comprehensive immune scoring system (ISS
) based on 6 immunosuppressive ligands (NECTIN2, CEACAM1, HMGB1, SIGLEC6, CD44, and CD155) using the LASSO method to improve prognostic accuracy and provide an additional selection strategy for adjuvant chemotherapy of gastric cancer (GC). The results show that ISS
is an independent prognostic factor and a supplement of TNM stage for GC patients, and it can improve their prognosis prediction accuracy; in addition, it can distinguish GC patients with better prognosis from those with high prognostic nutritional index score; furthermore, ISS
can also be used as a tool to select GC patients who would benefit from adjuvant chemotherapy independent of their TNM stages, MSI status and EBV status.
The expression pattern and role of circular RNAs (circRNAs) in the pathogenesis of gastric cancer (GC) and their underlying mechanisms remain unresolved. In this study, we identified differentially ...expressed circRNAs by a circRNA microarray and verified the results by quantitative reverse transcription‐polymerase chain reaction using 117 clinical samples. Cell Counting Kit‐8, wound healing, Transwell, and tumorsphere formation assays were conducted to assess the effects of circ‐CEP85L on cell proliferation and invasion in vitro. Mouse intraperitoneal injection models were used to assess the functions of circ‐CEP85L in vivo. Luciferase reporter assays, fluorescence in situ hybridization, and rescue experiments were performed to elucidate the underlying mechanism of circ‐CEP85L. We found that circ‐CEP85L, which has not been studied in GC, was significantly downregulated in GC tissues and that decreased circ‐CEP85L expression correlated significantly with a worse prognosis. The knockdown of circ‐CEP85L promoted the proliferation and invasion of GC cells, which was reversed by overexpression of circ‐CEP85L. Furthermore, inhibition of circ‐CEP85L promoted tumor growth in vivo. Mechanistically, circ‐CEP85L was confirmed to be a direct target of miR‐942‐5p. In addition, rescue experiments indicated that circ‐CEP85L is able to inhibit the proliferation and invasion of GC cells by sponging miR‐942‐5p. Finally, western blot assays verified that the downregulation of miR‐942‐5p efficiently reversed the inhibition of NFKBIA induced by circ‐CEP85L overexpression. Therefore, we conclude that circ‐CEP85L promotes NFKBIA expression by acting as a sponge of miR‐942‐5p; thus, inhibiting GC proliferation and invasion. circ‐CEP85L is a potential target in the treatment of GC.
The role of circular RNAs in gastric cancer (GC) and their underlying mechanisms remain unresolved. In this study, we demonstrated that circ‐CEP85L promotes NFKBIA expression by acting as a sponge of miR‐942‐5p, thus inhibiting GC proliferation and invasion. Targeting circ‐CEP85L may have promising prospects in GC therapy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
This study evaluated the safety, effectiveness, and feasibility of indocyanine green (ICG) tracing in guiding lymph-node (LN) dissection during laparoscopic D2 radical gastrectomy in ...patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC).
Method
We retrospectively analyzed data on 313 patients with clinical stage of cT1-4N0-3M0 who underwent laparoscopic radical gastrectomy after NAC between February 2010 and October 2020 from two hospitals in China. Grouped according to whether ICG was injected. For the ICG group (
n
= 102) and non-ICG group (
n
= 211), 1:1 propensity matching analysis was used.
Results
After matching, there was no significant difference in the general clinical pathological data between the two groups (ICG vs. non-ICG: 94 vs. 94). The average number of total LN dissections was significantly higher in the ICG group and lower LN non-compliance rate than in the non-ICG group. Subgroup analysis showed that among patients with LN and tumor did not shrink after NAC, the number of LN dissections was significantly more and LN non-compliance rate was lower in the ICG group than in the non-ICG group. Intraoperative blood loss was significantly lesser in the ICG group than in the non-ICG group, while the recovery and complications of the two groups were similar.
Conclusion
For patients with poor NAC outcomes, ICG tracing can increase the number of LN dissections during laparoscopic radical gastrectomy, reduce the rate of LN non-compliance, and reduce intraoperative bleeding. Patients with AGC should routinely undergo ICG-guided laparoscopic radical gastrectomy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background Application of indocyanine green (ICG) fluorescence imaging is effective in guiding laparoscopic radical lymphadenectomy for gastric cancer. However, the optimal approach for indocyanine ...green injection is controversial. Therefore, the objective of this study was aimed to compare the efficacy and ICG injection between the preoperative submucosal and intraoperative subserosal approaches for lymph node (LN) tracing during laparoscopic gastrectomy. Method This randomized controlled trial (ClinicalTrials.gov, NCT04219332) included 266 patients with potentially resectable gastric cancer (cT1-T4a, N0/+, M0) enrolled from a tertiary teaching center between December 2019 and October 2020. The primary endpoint was total number of retrieved LNs. Results In total, 259 patients (n = 130 and n = 129 in the submucosal and subserosal groups, respectively) were included in the per-protocol analysis. There are no significant differences in total number of retrieved LNs between the two groups (49.8 vs. 49.2, P = 0.713). The rate of LN noncompliance in the submucosal group was comparable to that in the subserosal group (32.3% vs. 33.3%, P = 0.860). No significant difference was found between the submucosal and subserosal groups in terms of the incidence (17.7% vs. 16.3%; P = 0.762) or severity of postoperative complications. The mean fluorescence cost in the submucosal group was higher than that in the subserosal group ($335.3 vs. $182.4; P < 0.001). The overall treatment satisfaction score was lower in the submucosal group than in the subserosal group (70.5 vs. 76.1%, P = 0.048). Conclusion ICG administered by subserosal injection was comparable to that administered by submucosal injection for lymph node tracing in gastric cancer. However, the former approach imposed a lower economic and mental burden on patients undergoing laparoscopic D2 lymphadenectomy. Trial registration ClinicalTrials.gov, NCT04219332. Keywords: Gastric cancer, Indocyanine green, Submucosal approach, Subserosal approach, Lymphadenectomy
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The biological functions of circular RNAs (circRNAs) in gastric cancer (GC) remain largely unexplored. Here, we identified that circ-RanGAP1 was significantly upregulated in both GC tissues and ...exosomes from the plasma of GC patients. High circ-RanGAP1 expression was closely associated with an advanced TNM stage, lymph node metastases, and worse survival. Inhibition of circ-RanGAP1 decreased GC cell invasion and migration in vitro. Overexpression of circ-RanGAP1 had the opposite effect. Additionally, circ-RanGAP1 silencing remarkably suppressed tumor growth and metastasis of GC in vivo. Mechanistically, circ-RanGAP1 sponged miR-877–3p to upregulate VEGFA expression. Overexpression of miR-877–3p reversed the biological functions mediated by circ-RanGAP1 in GC cells. Interestingly, we demonstrated that circ-RanGAP1 was upregulated in plasma exosomes from preoperative GC patients. More importantly, the plasma exosomes derived from these patients enhanced the migration and invasion potential of GC cells. Overall, the circ-RanGAP1-mediated miR-877–3p/VEGFA axis promotes GC progression. Our findings suggest that circ-RanGAP1 might act as a potential prognostic biomarker and therapeutic target for GC treatment.
•Circ-RanGAP1 is up regulated in gastric cancer (GC) tissues and plasma exosomes.•Circ-RanGAP1 overexpression is correlated with poor prognosis in GC.•Circ-RanGAP1 promotes GC invasion and metastasis both in vitro and in vivo.•Circ-RanGAP1 promotes GC progression through miR-877–3p/VEGFA axis.•Exosomal circ-RanGAP1 may be a promising application in GC diagnosis and treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Early metastasis is responsible for frequent relapse and high mortality of hepatocellular carcinoma (HCC), but its underlying mechanisms remain unclear. Epithelial–mesenchymal transition (EMT) has ...been considered a key event in metastasis. Based on histological examination of serial HCC sections and three‐dimensional reconstruction, we found a novel and prevalent vascular pattern, vessels that encapsulated tumor clusters (VETC) and formed cobweb‐like networks. The presence of VETC (VETC+) predicted higher metastasis and recurrence rates of HCC. Using clinical samples and mouse xenograft models, we further showed that VETC was composed of functional vessels with blood perfusion and induced by tumor cells at the early stage of HCC. Subsequent investigations revealed that HCC cell–derived angiopoietin‐2 was a prerequisite for VETC formation and that the VETC pattern was a critical factor promoting HCC metastasis as knockdown of angiopoietin‐2 abolished this vascular pattern and consequently attenuated in vivo tumor metastasis. Interestingly, abrogation of EMT by knockdown of Snail or Slug significantly diminished in vivo metastasis of VETC– xenografts but did not affect that of VETC+ ones, although silencing of Snail or Slug substantially reduced the in vitro migration of both VETC+ and VETC– HCC cells. In contrast to human VETC– cases, EMT signatures were rarely observed in VETC+ cases with metastatic potential. Further analysis revealed that VETC provided an efficient metastasis mode by facilitating the release of whole tumor clusters into the bloodstream. Conclusion: Our findings identify a novel metastasis mechanism that relies on vascular pattern but is independent of EMT, which may provide new targets for antimetastasis therapy and offer a basis for selecting patients who may benefit from certain molecularly targeted drugs. (Hepatology 2015;62:452–465
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Tree shrews have a close relationship to primates and have many advantages over rodents in biomedical research. However, the laek of gene manipulation methods has hindered the wider use of this ...animal. Spermatogonial stem cells （SSCs） have been successfully expanded in culture to permit sophisticated gene editing in the mouse and rat. Here, we describe a culture system for the long-term expansion of tree shrew SSCs without the loss of stem cell properties. In our study, thymus cell antigen 1 was used to enrich tree shrew SSCs. RNA-sequencing analysis revealed that the Wnt/β-catenin signaling pathway was active in undifferentiated SSCs, but was downregulated upon the initiation of SSC differentiation. Exposure of tree shrew primary SSCs to recombinant Wnt3a protein during the initial passages of culture enhanced the survival of SSCs. Use of tree shrew Sertoli cells, but not mouse embryonic fibroblasts, as feeder was found to be necessary for tree shrew SSC proliferation, leading to a robust cell expansion and long-term culture. The expanded tree shrew SSCs were transfected with enhanced green fluorescent protein （EGFP）-expressing lentiviral vectors. After transplantation into sterilized adult male tree shrew＇s testes, the EGFP-tagged SSCs were able to restore spermatogenesis and successfully generate transgenic offspring. Moreover, these SSCs were suitable for the CRISPR/Cas9-mediated gene modification. The development of a culture system to expand tree shrew SSCs in combination with a gene editing approach paves the way for precise genome manipulation using the tree shrew.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
IMPORTANCE: The application of indocyanine green (ICG) imaging in laparoscopic radical gastrectomy is in the preliminary stages of clinical practice, and its safety and efficacy remain controversial. ...OBJECTIVE: To investigate the safety and efficacy of ICG near-infrared tracer-guided imaging during laparoscopic D2 lymphadenectomy in patients with gastric cancer. DESIGN, SETTING, AND PARTICIPANTS: Patients with potentially resectable gastric adenocarcinoma (clinical tumor stage cT1-cT4a, N0/+, M0) were enrolled in a prospective randomized clinical trial at a tertiary referral teaching hospital between November 2018 and July 2019. Patients were randomly assigned to the ICG group or the non-ICG group. The number of retrieved lymph nodes, rate of lymph node noncompliance, and postoperative recovery data were compared between the groups in a modified intention-to-treat analysis. Statistical analysis was performed from August to September 2019. INTERVENTIONS: The ICG group underwent laparoscopic gastrectomy using near-infrared imaging after receiving an endoscopic peritumoral injection of ICG to the submucosa 1 day before surgery. MAIN OUTCOMES AND MEASURES: Total number of retrieved lymph nodes. RESULTS: Of 266 participants randomized, 133 underwent ICG tracer-guided laparoscopic gastrectomy, and 133 underwent conventional laparoscopic gastrectomy. After postsurgical exclusions, 258 patients were included in the modified intention-to-treat analysis, which comprised 129 patients (86 men and 43 women; mean SD age, 57.8 10.7 years) in the ICG group and 129 patients (87 men and 42 women; mean SD age, 60.1 9.1 years) in the non-ICG group. The mean number of lymph nodes retrieved in the ICG group was significantly more than the mean number retrieved in the non-ICG group (mean SD, 50.5 15.9 lymph nodes vs 42.0 10.3 lymph nodes, respectively; P < .001). Significantly more perigastric and extraperigastric lymph nodes were retrieved in the ICG group than in the non-ICG group. In addition, the mean total number of lymph nodes retrieved in the ICG group within the scope of D2 lymphadenectomy was also significantly greater than the mean number retrieved in the non-ICG group (mean SD, 49.6 15.0 lymph nodes vs 41.7 10.2 lymph nodes, respectively; P < .001). The lymph node noncompliance rate of the ICG group (41 of 129 patients 31.8%) was lower than that of the non-ICG group (74 of 129 patients 57.4%; P < .001). The postoperative recovery process was comparable, and no significant difference was found between the ICG and non-ICG groups in the incidence (20 of 129 patients 15.5% vs 21 of 129 16.3%, respectively; P = .86) or severity of complications within 30 days after surgery. CONCLUSIONS AND RELEVANCE: Indocyanine green can noticeably improve the number of lymph node dissections and reduce lymph node noncompliance without increased complications in patients undergoing D2 lymphadenectomy. Indocyanine green fluorescence imaging can be performed for routine lymphatic mapping during laparoscopic gastrectomy, especially total gastrectomy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03050879
OBJECTIVE:To evaluate the short-term outcomes of patients with gastric cancer (GC) who received robotic distal gastrectomy (RDG) or laparoscopic distal gastrectomy (LDG).
SUMMARY BACKGROUND ...DATA:Despite the increasing use of RDG in patients with GC, its safety and efficacy compared to those of LDG have not been elucidated in a randomized controlled trial (RCT).
METHODS:Three hundred patients with cT1-4a and N0/+ between September 2017 and January 2020 were enrolled in this RCT at a high-volume hospital in China. The short-term outcomes were compared between the groups.
RESULTS:The modified intention-to-treat analysis included data from 283 patients (RDG groupn = 141) and (LDG groupn = 142). Patients in the RDG group exhibited faster postoperative recovery, milder inflammatory responses, and reduced postoperative morbidity (9.2% vs. 17.6%, respectively, p = 0.039). Higher extraperigastric lymph nodes (LNs) were retrieved in the RDG group (17.6 ± 5.8 vs. 15.8 ± 6.6, p = 0.018) with lower noncompliance rate (7.7% vs. 16.9%, respectively, p = 0.006). Additionally, patients in the RDG group were more likely to initiate adjuvant chemotherapy earlier (median interquartile range postoperative days28 24–32 vs. 32 26–42, p = 0.003). Although total hospital costs were higher in the robotic group than in the laparoscopic group, the direct cost was lower for RDG than for LDG (all p < 0.001).
CONCLUSIONS:RDG is associated with a lower morbidity rate, faster recovery, milder inflammatory responses, and improved lymphadenectomy. Additionally, faster postoperative recovery in the RDG group enables early initiation of adjuvant chemotherapy. Our results provide evidence for the application of RDG in patients with GC.
Systemic inflammatory factors can predict the survival prognosis of gastric cancer (GC) patients after neoadjuvant chemotherapy (NACT). However, whether longitudinal changes in systemic inflammatory ...factors are associated with short - and long-term outcomes has not been reported.
This study is a retrospective analysis of 216 patients with advanced gastric cancer who received NACT between January 2011 and June 2019, comparing receiver operating characteristic (ROC) curves for screening suitable inflammatory markers. Group-based trajectory modeling (GBTM) was used to analyze longitudinal changes in inflammatory markers during NACT to identify different potential subgroups and to compare postoperative complications, recurrence-free survival (RFS), and overall survival (OS) among subgroups.
Ultimately, neutrophil-lymphocyte ratio (NLR) had the highest area under the curve (AUC) value in predicting prognosis was included in the GBTM analysis. Three trajectories of NLR were obtained: Stable group (SG) (n = 89), Ascent-descend group (ADG) (n = 80) and Continuous descend group (CDG) (n = 47). Compared with SG, ADG and CDG are associated with an increased risk of postoperative recurrence and death. The median time of RFS and OS of SG was longer than that of ADG and CDG (median RFS 81 vs. 44 and 22 months; median OS 69 vs. 41 and 30 months). In addition, CDG had significantly higher postoperative serious complications than SG and ADG (17 (36.2%) vs. 17 (19.1%) and 12 (15.0%); p = 0.005).
There were different trajectories of NLR during NACT, and these potential trajectories were significantly associated with severe postoperative complications, recurrence, and mortality in patients with GC.
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