Safety and feasibility of minimally invasive gastrectomy after neoadjuvant immunotherapy for locally advanced gastric cancer: a propensity score-matched analysis in China.

Background: The effect of neoadjuvant immunotherapy on minimally invasive gastrectomy (MIG) for locally advanced gastric cancer (LAGC) remains controversial. This study aimed to compare short-term outcomes between MIG after neoadjuvant chemo-immunotherapy (NICT-MIG) and MIG after neoadjuvant chemotherapy alone (NCT-MIG), and determine risk factors for post-operative complications (POCs). Methods: This retrospective study included clinicopathologic data from 193 patients who underwent NCT-MIG or NICT-MIG between January 2020 and February 2023 in the Department of General Surgery, Chinese People's Liberation Army General Hospital First Medical Center (Beijing, China). Propensity score-matched analysis at a ratio of 1:2 was performed to reduce bias from confounding patient-related variables and short-term outcomes were compared between the two groups. Results: The baseline characteristics were comparable between 49 patients in the NICT-MIG group and 86 patients in the NCT-MIG group after propensity score matching. Objective and pathologic complete response rates were significantly higher in the NICT-MIG group than in the NCT-MIG group (P < 0.05). The overall incidence of treat-related adverse events, intraoperative bleeding, operation time, number of retrieved lymph nodes, time to the first flatus, post-operative duration of hospitalization, overall morbidity, and severe morbidity were comparable between the NCT-MIG and NICT-MIG groups (P > 0.05). By multivariate logistic analysis, estimated blood loss of >200 mL (P = 0.010) and prognostic nutritional index (PNI) score of <45 (P = 0.003) were independent risk factors for POCs after MIG following neoadjuvant therapy. Conclusions: Safety and feasibility of NICT were comparable to those of NCT in patients undergoing MIG for LAGC. Patients with an estimated blood loss of >200 mL or a PNI score of <45 should be carefully evaluated for increased POCs risk.

Comparison of Clinical Characteristics, Therapy, and Short-Term Prognosis between Blunt and Penetrating Abdominal Trauma: A Multicentric Retrospective Cohort Study.

Objective: Large-scale studies on the characteristics and management of abdominal trauma in megacities in China are lacking. The aim of this study was to analyze and present the clinical patterns and treatment status of abdominal trauma in regional medical centers. Methods: Cases of abdominal trauma treated at seven medical centers in Beijing from 2010 to 2021 were collected. Clinical information about age, sex, injury cause, geographic distribution, abbreviated injury scale/injury severity score (AIS/ISS) value, injury-hospital time, preoperative time, surgically identified organ injuries, type of surgery, causes of reoperation and 90-day mortality was included in this study. Clinical characteristics, treatment methods, and short-term prognoses (90-days survival) were compared between blunt abdominal trauma (BAT) and penetrating abdominal trauma (PAT) cases. Non-normally distributed data are described as medians (IQR), and the Mann‒Whitney U test was performed; qualitative data were analyzed using the X2 test. Univariate and multivariate survival analyses were performed by the Cox proportional hazards model. Results: A total of 553 patients (86.98% male) with a median age of 36.50 (27.00-48.00) years were included. The BAT group had a significantly higher proportion of serious injury (P=0.001), lower initial hemoglobin level (P=0.001), and a lower laparoscopy surgery rate (P=0.044) compared to the PAT group. Additionally, more BAT cases were from the area around Beijing (P=0.008) and a longer injury-regional hospital time (10.47 (5.18-22.51) hours vs. 7.00 (3.80-15.38) hours, P=0.001). In the hollow viscus injury subgroup, the BAT group had a significantly longer injury-regional hospital time and preoperative time compared to the PAT group (injury-regional hospital time: 10.23 (6.00-21.59) hours vs. 7.07 (3.99-13.85) hours, P=0.002; preoperative time: 3.02 (2.01-5.58) hours vs. 2.81 (1.85-3.63) hours, P=0.047). The overall 90-day mortality was 11.9%, and longer injury-regional hospital time (HR: 1.01, 95% CI: 1.00-1.02, P=0.008), receipt of ICU treatment (HR: 4.69, 95% CI: 2.54-8.65, P=0.001), and severe ISSs (ISS > 25 vs. ISS < 16, HR: 2.78, 95% CI: 1.38-5.601, P=0.004) had a worse impact on survival. Conclusion: More patients with BAT were transferred to higher-level hospital, leading to significantly longer prehospital and preoperation time. In the subgroup of hemodynamically stable individuals, more patients with BAT experienced hollow viscus injuries. For those patients, aggressive diagnostic laparoscopic exploration may be beneficial. Patients with longer injury-regional hospital intervals, the need for ICU care, and higher injury severity scores (ISSs) suffered from worse prognoses.

Total versus proximal gastrectomy for proximal gastric cancer after neoadjuvant chemotherapy: a multicenter retrospective propensity score-matched cohort study.

BACKGROUND: This study aimed to analyze and compare the short-term and long-term outcomes of proximal gastrectomy (PG) and total gastrectomy (TG) in patients with locally advanced proximal gastric cancer (GC) following neoadjuvant chemotherapy (NACT). METHOD: A multicenter retrospective cohort study and propensity score matching (PSM) were employed. The authors examined 367 patients with proximal GC who received NACT followed by PG ( n =164) or TG ( n =203) at two Chinese medical institutions between December 2009 and December 2022. Clinical and pathological parameters, postoperative complications, and 5-year overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups. The dissection status and metastasis rate of each lymph node station were assessed. RESULTS: After PSM, 80 patients were enrolled in both TG and PG group, and baseline characteristics were comparable between the groups (all P >0.05). The TG group had a higher total number of lymph nodes retrieved ( P <0.001) and longer operative time ( P =0.007) compared to the PG group. The incidence of Clavien-Dindo grade II or higher postoperative complications was similar between the TG group (21.3%, 17/80) and the PG group (17.5%, 14/80) ( P =0.689). The 5-year OS rates were 68.4 for the PG group and 66.0% for the TG group ( P =0.881), while the 5-year RFS rates were 64.8 and 61.9%, respectively ( P =0.571), with no statistically significant differences. Metastasis rates at lymph node stations #4d, #5, #6, and #12a were notably low in the TG group, with values of 2.74, 0.67, 1.33, and 1.74%, respectively. CONCLUSION: For proximal GC patients following NACT, PG maintains comparable curative potential and oncological efficacy to TG, making it a safe option.

MT1M regulates gastric cancer progression and stemness by modulating the Hedgehog pathway protein GLI1.

Gastric cancer (GC) is a highly prevalent and aggressive malignancy with a poor prognosis. Recent evidence suggested that metallothionein 1 M (MT1M) may play a critical role in cancer development, progression, and drug resistance; however, its role in GC remains largely unknown. In this study, we investigated the expression and function of MT1M in GC both in vitro and in vivo. We found that MT1M expression was significantly downregulated in GC tissues and cell lines. Decreased expression of MT1M was associated with worse clinical prognosis, particularly in patients treated with 5-fluorouracil. Low expression of MT1M was indicative of poor overall survival (OS, HR 0.56 [95% CI 0.37-0.84], P < 0.005), first progression survival (FP, HR 0.54 [95% CI 0.36-0.79], P < 0.005), and post-progression survival (PPS, HR 0.65 [95% CI 0.45-0.94], P < 0.05). We also demonstrated that overexpression of MT1M inhibited cell proliferation and induced apoptosis in GC cells and in tumor xenografts, and it improved chemosensitivity to 5-fluorouracil. Furthermore, we found that MT1M overexpression could inhibit stem cell characteristics by targeting GLI1 and affecting GLI1 ubiquitination. Collectively, these findings indicated that MT1M may act as a tumor suppressor in GC and could serve as a potential therapeutic target to attenuate stemness and chemotherapy resistance of GC.

Five-year long-term comparison of robotic and laparoscopic gastrectomy for gastric cancer: a large single-center cohort study.

BACKGROUND: Robotic gastrectomy (RG) has been reported to be technically feasible and safe for patients with gastric cancer. However, 5-year long-term survival and recurrence outcomes for advanced gastric cancer have rarely been reported. This study aimed to compare the long-term oncologic outcomes between RG and laparoscopic gastrectomy (LG) for gastric cancer. METHODS: The general clinicopathological data of 1905 consecutive patients who underwent RG and LG were retrospectively collected at the Chinese People's Liberation Army General Hospital between November 2011 and October 2017. Propensity score matching (PSM) was used to match groups. The primary endpoints were 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: After PSM, a well-balanced cohort of 283 patients in the RG group and 701 patients in the LG group were included in the analysis. The 5-year cumulative DFS rates were 67.28% in the robotic group and 70.41% in the laparoscopic group. The 5-year OS rate was 69.01% in the robotic group and 69.58% in the laparoscopic group. No significant differences in Kaplan-Meier survival curves for DFS (HR = 1.08, 95% CI 0.83-1.39, Log-rank P = 0.557) and OS (HR = 1.02, 95% CI 0.78-1.34, Log-rank P = 0.850) were observed between the 2 groups. In the subgroup analyses for potential confounding variables, there were no significant differences in 5-year DFS and 5-year OS survival between the 2 groups (P > 0.05), except for patients with pathological stage III and pathological stage N3 (P < 0.05). CONCLUSION: For patients with early gastric cancer, robotic and laparoscopic approaches have similar long-term survival. For patients with advanced gastric cancer, further studies need to be conducted to assess the long-term survival outcomes of RG.

Surgical starting time of the day and survival in gastric cancer.

Previous studies indicate differences in short-term postoperative outcomes depending on the surgical starting time of the day, but long-term data are lacking. The aim of this study was to clarify if surgical starting time of the day influences long-term survival in gastric cancer patients. This cohort study consecutively included 2728 patients who underwent curatively intended gastrectomy for gastric cancer in 2011-2015 at a high-volume hospital in China, with follow-up until June 2019. Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for 3-year all-cause mortality, adjusted for age, sex, health insurance, pathological tumor stage, surgical approach, neoadjuvant therapy, and weekday of surgery. Compared with patients with early starting time of gastrectomy (08:00-09:29), the point estimates for 3-year all-cause mortality were modestly increased in patients with a starting time in the middle of day (09:30-13:29; HR 1.15, 95% CI 0.97 to 1.37) and later (13:30-21:25; HR 1.10, 0.91 to 1.32). The corresponding HRs were increased particularly in patients who underwent laparoscopic gastrectomy (HR 1.54, 1.10 to 2.14 and HR 1.59, 1.12 to 2.25, respectively) and in those with stage II tumors (HR 1.74, 1.11 to 2.73 and HR 1.60, 1.00 to 2.58, respectively). Our study indicated that in patients who underwent laparoscopic gastrectomy and in those who with stage II tumors, starting surgery in the early morning might be associated with better long-term survival.

Combining neoadjuvant chemotherapy with PD-1/PD-L1 inhibitors for locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: A systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) have shown promising prospects in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) immunotherapy, but their efficacy in neoadjuvant settings remains unclear. This study aimed to assess the efficacy and safety of integrating programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors into neoadjuvant chemotherapy (NACT) of GC/GEJC treatment. Methods: PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and main oncology conference databases were systematically searched up to 19 November 2022, and randomized controlled trials (RCTs) and cohort studies that evaluated the efficacy and safety of PD-1/PD-L1 inhibitors plus NACT were included. The main outcomes were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, and treatment-related adverse events (TRAEs). Results: A total of 753 patients from 20 prospective studies were included in this meta-analysis. The pooled pCR and MPR rates from studies reporting were 21.7% [95% confidence interval (CI), 18.1%-25.5%] and 44.0% (95% CI, 34.1%-53.8%), respectively. The pooled incidence rate of total TRAEs was 89.1% (95% CI, 82.7%-94.3%), and the incidence rate of grade 3 to 4 TRAEs was 34.4% (95% CI, 17.8%-66.5%). The pooled R0 resection rate was reported to be 98.9% (95% CI, 97.0%-99.9%). Subgroup analysis has not found significant differences in efficacy and safety among different PD-1/PD-L1 inhibitors. Moreover, the efficacy in patients with positive PD-L1 expression (combined positive score ≥1) was comparable with that in the entire study population [pCR, 22.5% vs. 21.2% (p > 0.05); MPR, 48.6% vs. 43.7% (p > 0.05)]. Conclusion: This systematic review and meta-analysis found that PD-1/PD-L1 inhibitors combined with NACT for locally advanced GC/GEJC were well tolerated and may confer therapeutic advantages. The integration of ICIs into NACT has shown the potential for application in any PD-L1 expression population.

Multilevel proteomic analyses reveal molecular diversity between diffuse-type and intestinal-type gastric cancer.

Diffuse-type gastric cancer (DGC) and intestinal-type gastric cancer (IGC) are the major histological types of gastric cancer (GC). The molecular mechanism underlying DGC and IGC differences are poorly understood. In this research, we carry out multilevel proteomic analyses, including proteome, phospho-proteome, and transcription factor (TF) activity profiles, of 196 cases covering DGC and IGC in Chinese patients. Integrative proteogenomic analysis reveals ARIDIA mutation associated with opposite prognostic effects between DGC and IGC, via diverse influences on their corresponding proteomes. Systematical comparison and consensus clustering analysis identify three subtypes of DGC and IGC, respectively, based on distinct patterns of the cell cycle, extracellular matrix organization, and immune response-related proteins expression. TF activity-based subtypes demonstrate that the disease progressions of DGC and IGC were regulated by SWI/SNF and NFKB complexes. Furthermore, inferred immune cell infiltration and immune clustering show Th1/Th2 ratio is an indicator for immunotherapeutic effectiveness, which is validated in an independent GC anti-PD1 therapeutic patient group. Our multilevel proteomic analyses enable a more comprehensive understanding of GC and can further advance the precision medicine.

Defining the impact of platelet-to-lymphocyte ratio on patient survival with gastric neuroendocrine neoplasm: a retrospective cohort analysis.

BACKGROUND: Gastric neuroendocrine neoplasm (g-NEN) is a rare but heterogeneous neoplasm, with an increasing incidence yearly. Conventional prognostic markers of g-NEN remain limited which could only be detected after surgery. There is an urgent need to explore new prognostic markers for g-NEN patients. This study aimed to investigate the prognostic value of platelet-to-lymphocyte, ratio (PLR) and the association between PLR and body mass index (BMI) in patients with gastric neuroendocrine neoplasms (g-NEN). METHODS: A retrospective cohort of patients with g-NEN from January 2001 through June 2016 was examined. The prognostic significance of PLR was determined by multiple regression analysis in different models. Stratified analysis was performed to examine the prognostic value of PLR at different BMI levels. RESULTS: In total, 238 patients were enrolled. Those with higher PLRs tended to undergo open surgery, had larger tumor sizes, were diagnosed more frequently with neuroendocrine carcinoma, and had higher tumor grades. PLR was significantly associated with the survival of patients with g-NEN. With PLR increased per standard deviation, the all-cause mortality risk of patients with g-NEN increased by 67%, 63%, and 54% in the crude (HR = 1.67, 95% CI 1.32-2.12, P < 0.001), minimally adjusted (HR = 1.63, 95% CI 1.28-2.08, P < 0.001), and fully adjusted (HR = 1.54, 95% CI 1.202-1.98, P = 0.001) models, respectively. Patients with higher PLR (quartile 4, ≥ 187) had a 1.8-fold increase in all-cause mortality risk compared with those with lower PLR (quartile 1-3, < 187). Furthermore, there was a significant interaction effect between BMI subgroups and PLR in predicting the survival of patients with g-NEN (PLR regarded as a continuous variable: all P for interaction < 0.05 in the crude, minimally adjusted, and fully adjusted models; PLR regarded as a categorical variable: P for interaction < 0.05 in the fully adjusted model). Patients with g-NEN with the characteristics of higher PLR (quartile 4, ≥ 187) and non-obesity (BMI < 25 kg/m2) had worse survival than others (P < 0.05). CONCLUSION: The inflammation marker PLR has an independent prognostic value for patients with g-NENs, and high PLR combined with non-obesity increases the mortality risk of these patients.

MiR-378a-3p acts as a tumor suppressor in gastric cancer via directly targeting RAB31 and inhibiting the Hedgehog pathway proteins GLI1/2.

OBJECTIVE: To improve the prognosis of patients with gastric cancer (GC), more effective therapeutic targets are urgently needed. Increasing evidence indicates that miRNAs are involved in the progression of various tumors, and RAS-associated protein in the brain 31 (RAB31) is upregulated and promotes the progression of multiple malignant tumors. Here, we focused on identifying RAB31-targeted miRNAs and elucidating their potential mechanism in the progression of GC. METHODS: RAB31 and miR-378a-3p expression levels were detected in paired fresh GC tissues and GC cell lines. Bioinformatics analysis was used to predict the miRNAs targeting RAB31 and the relationships between RAB31 and other genes. Dual-luciferase reporter assays were applied to verify the targeted interaction relationship. CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of GC cells. Tumorsphere formation assays were performed to assess the stemness of gastric cancer stem cells. Related proteins were detected by Western blot. Xenograft assays in nude mice were performed to explore the effect of miR-378a-3p in vivo. RESULTS: We report the first evidence that miR-378a-3p is downregulated in GC, whereas its overexpression inhibits proliferation, invasion, and migration as well as promotes apoptosis in GC cells. Mechanistically, miR-378a-3p inhibits the progression of GC by directly targeting RAB31. Restoring RAB31 expression partially offsets the inhibitory effect of miR-378a-3p. Further research revealed that miR-378a-3p inhibits GLI1/2 in the Hedgehog signaling pathway and attenuates the stemness of gastric cancer stem cells. Finally, xenograft assays showed that miR-378a-3p inhibits GC tumorigenesis in vivo. CONCLUSIONS: MiR-378a-3p inhibits GC progression by directly targeting RAB31 and inhibiting the Hedgehog signaling pathway proteins GLI1/2.

Prognostic value of lymph node density on cancer staging system for gastric cancer without distal metastasis: a population-based analysis of SEER database.

BACKGROUND: Accurate tumor staging is the cornerstone of tumor treatment. Current tumor staging system for gastric cancer (GC) is based on regional positive lymph nodes while ignoring the total number of examined lymph nodes. We aim to assess the prognostic value of lymph node density (LND), the ratio of positive nodes to the total number examined nodes, in GC without distal metastasis. METHODS: Clinical information of patients with histologically confirmed GC and without distal metastasis was identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The X-Tile software was used to identify the ideal prognosis-related cutoff point for LND. The prognostic value of LND on cancer-specific survival (CSS) and overall survival (OS) was assessed in Cox regression models. Subgroup analysis stratified by LND was performed on current lymph node staging system to further explore the interaction between LND and current lymph node staging system. RESULTS: A total of 4281 participants were identified from the SEER database for the final analysis. The optimal prognosis-related cutoff values of LND were calculated as 0.1 and 0.4, and LND was divided into three levels: LND1 (< 0.1), LND2 (> = 0.1, < 0.4), and LND3 (> = 0.4). LND3 was associated with worse CSS and OS in GC patients. Compared to patients with LND1, those with LND2 and LND3 had 2.43 (HR = 2.43, 95% CI 2.09-2.84, P < 0.001) and 4.69 (HR = 4.69, 95% CI 4.02-5.48, P < 0.001) folds increase in mortality in CSS, respectively. Similar results were found in the evaluation of OS in GC patients. Subgroup analysis stratified by LND also found that patients in the same current lymph node stage still had different prognosis due to the different LND levels after adjustment for other prognosis-related covariates (all P values < 0.001). CONCLUSION: LND is an independent prognostic factor for GC without distal metastasis. In the current lymph node staging system, LND has potential value in further accurately classifying GC patients without distal metastasis.

Rspondin-1 contributes to the progression and stemness of gastric cancer by LGR5.

Gastric cancer is a one of the most common malignant tumors with poor prognosis worldwide. Leucine-rich G-protein-coupled receptor 5 (LGR5) is determined as a modulator of Wnt signaling cascade and R-spondins are a family of secretory agonists in the Wnt signaling and act as ligands to interact with LGR5. However, the function of Rspondin-1 in GC remains obscure. Here, we identified the effect of Rspondin-1 on GC progression. Rspondin-1 and LGR5 were upregulated in clinical gastric cancer tissues. CCK-8 assay revealed that the viability of GC cells was reduced by Rspondin-1 depletion and enhanced by Rspondin-1 overexpression. The depletion of Rspondin-1 decreased while the overexpression of Rspondin-1 increased the numbers of colony formation and Edu-positive GC cells. The depletion of Rspondin-1 attenuated the invasion and migration ability of GC cells. Moreover, sphere formation assays revealed that the knockdown of Rspondin-1 reduced the stemness of GC cells. The expression of cancer stem cell markers, including Nanog, OCT3/4, and SOX2 were suppressed by Rspondin-1 depletion in GC cells. Rspondin-1 induced tumor growth of gastric cancer cells in vivo. Mechanically, the cell viability and invasion suppressed by the depletion of Rspondin-1 in GC cells were rescued by LGR5 overexpression. Besides, the overexpression of LGR5 reversed Rspondin-1 knockdown-inhibited Nanog and OCT3/4 expression. Consequently, we concluded that Rspondin-1 contributes to the progression and stemness of gastric cancer by LGR5.

Can a single-port robot be safely used for robotic total gastrectomy for advanced gastric cancer? First experience using the da Vinci SP platform.

Background: Many studies have shown the operative feasibility and safety of robotic gastrectomy. Surgeons are pursuing single-port (SP) surgery to leverage the advantages of minimally invasive gastrectomy. The purpose of this study was to describe technical considerations and short-term outcomes from the first reported SP robotic total gastrectomy (RTG) using the da Vinci SP platform. Methods: A 75-year-old patient with a body-mass index of 19.8 kg/m2 and clinical stage III cancer (cT3N+M0) underwent SP RTG on 22 January 2022 at the Department of General Surgery, the Chinese PLA General Hospital. All procedures were performed successfully using the da Vinci SP robotic platform. Results: The SP RTG was successfully performed with D2 lymphadenectomy including No. 10 lymph-nodes dissection and extracorporeal Roux-en-Y anastomosis. Except for subcutaneous emphysema, no severe adverse events occurred during the operation. According to a visual analogue scale (VAS), the subjective feeling of post-operative pain was given a VAS score of 3 of 10 on Post-Operative Day 1 (POD 1), 1 of 10 on POD 3, and 1 of 10 on POD 7. We removed the gastric tube on POD 2 and advised sipping water, a liquid diet, and a soft diet on PODs 2, 4, and 6, respectively. The patient was discharged without any complications on POD 8. Conclusion: RTG is technically feasible and safe using the da Vinci SP robotic platform. To our knowledge, this is the first study using the da Vinci SP platform in RTG for advanced gastric cancer in elderly patients. To verify its superior operative outcomes, further clinical trials are needed.

Skin chronological aging drives age-related bone loss via secretion of cystatin-A.

Although clinical evidence has indicated an association between skin atrophy and bone loss during aging, their causal relationship and the underlying mechanisms are unknown. Here we show that premature skin aging drives bone loss in mice. We further identify that cystatin-A (Csta), a keratinocyte-enriched secreted factor, mediates the effect of skin on bone. Keratinocyte-derived Csta binds the receptor for activated C-kinase 1 in osteoblast and osteoclast progenitors, thus promoting their proliferation but inhibiting osteoclast differentiation. Csta secretion decreases with skin aging in both mice and humans, thereby causing senile osteoporosis by differentially decreasing the numbers of osteoblasts and osteoclasts. In contrast, topical application of calcipotriol stimulates Csta production in the epidermis and alleviates osteoporosis. These results reveal a mode of endocrine regulation of bone metabolism in the skin, and identify Csta as an epidermally derived hormone linking skin aging to age-related bone loss. Enhancers of skin Csta levels could serve as a potential topical drug for treatment of senile osteoporosis.

MiR-144-3p inhibits gastric cancer progression and stemness via directly targeting GLI2 involved in hedgehog pathway.

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC. METHODS: Paired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo. RESULTS: GLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo. CONCLUSIONS: MiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression.

CircRNAs in gastric cancer: current research and potential clinical implications.

Gastric cancer (GC) has a dismal prognosis and is also one of the most commonly diagnosed malignancies worldwide. circRNAs are covalently closed circular RNA molecules without 5'-cap and a 3'-tail, currently listed among the broad noncoding RNA family. circRNAs participate in a variety of pathophysiological processes relevant to human diseases, especially malignancies, including GC. Compelling evidence has shown that circRNAs can function by sponging miRNAs, interacting with RNA binding proteins, and encoding proteins or peptides. Yet, our current understanding of these RNA circles remains very limited. Here, we overview the biogenesis, characteristics, functions, and degradation of circRNAs. Moreover, we give an account of the circRNAs that have been linked with GC, describing their functions and mechanisms of action in the context of GC. Next, we discuss the potential value of circRNAs as diagnostic or prognostic GC biomarkers and summarize future prospects, important questions, and challenges of circRNA-based therapeutics.

Proteomics provides individualized options of precision medicine for patients with gastric cancer.

While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.

Could neoadjuvant chemotherapy increase postoperative complication risk of laparoscopic total gastrectomy? A mono-institutional propensity score-matched study in China.

BACKGROUND: The potential survival benefit of neoadjuvant chemotherapy (NC) in patients with advanced gastric cancer has been widely recognized. With the development of minimally invasive surgery, which is represented by laparoscopy, the effect of NC on the safety of laparoscopic gastrectomy remains to be further explored. AIM: To compare the short-term outcomes of laparoscopic total gastrectomy (LTG) after NC (NC-LTG) with LTG alone. METHODS: A total of 92 patients who underwent NC-LTG and 381 patients who received LTG alone at the Chinese PLA General Hospital between September 2015 and September 2020 were retrospectively included in our study. We used propensity-score matching (PSM) to balance baseline bias. After 1:1 PSM, 73 patients were included in each group with no statistically significant difference in baseline characteristics. RESULTS: The NC-LTG group exhibited a longer operation time (244.10 ± 48.13 min vs 225.74 ± 45.33 min, P = 0.019) and increased intraoperative blood loss [150 (100-300) mL vs 100 (100-200) mL, P = 0.011] compared to the LTG group. The 30-d postoperative morbidity of the NC-LTG group was 20.5% (15/73), and that of the LTG group was 13.7% (10/73). There were no significant differences in 30-d severe complication rates or anastomotic leakage rates. Subgroup analysis showed that the patients with pTNM (pathological tumor-node-metastasis classification) T0N0-II in the NC-LTG group underwent a longer operation than the LTG group, while no significant difference was found in any perioperative index for the pTNM III patients. A multivariate analysis showed that an operation time longer than 240 min was an independent risk factor (odds ratio = 3.021, 95% confidence interval: 1.160-7.868, P = 0.024), while NC was not an independent risk factor for postoperative complications in LTG. CONCLUSION: Despite a longer operation time and more blood loss after NC-LTG, which indicate surgical difficulty, NC-LTG exhibits acceptable short-term outcomes compared to LTG, suggesting the safety and feasibility of NC-LTG.

Effect of preoperative nutrition therapy type and duration on short-time outcomes in gastric cancer patient with gastric outlet obstruction.

OBJECTIVE: To avoid perioperative complications caused malnutrition, nutrition therapy is necessary in gastric outlet obstruction (GOO) patients. Compared to parenteral nutrition (PN), enteral nutrition (EN) is associated with many advantages. This study aimed to investigate whether preoperative EN has beneficial clinical effects compared to preoperative PN in gastric cancer patients with GOO undergoing surgery. METHODS: According to the methods of preoperative nutrition therapy, 143 patients were divided into EN group (n=42) and PN group (n=101) between January 2013 and December 2017 at the Chinese People's Liberation Army General Hospital. Multiple logistic regression models were used to assess the association between the methods of preoperative nutrition therapy and postoperative day of flatus passage. The generalized additive model and two-piecewise linear regression model were used to calculate the inflection point of the preoperative nutritional therapy time on the postoperative day of flatus passage in the PN group. RESULTS: EN shortened the postoperative day of flatus passage in gastric cancer patients with GOO, which is a protective factor, especially in patients who underwent non-radical operations and the postoperative day of flatus passage reduced when the preoperative PN therapy was up to 3 d and a longer PN therapy (>3 d) did not accelerate the postoperative recovery of gastrointestinal functions. CONCLUSIONS: Preoperative EN therapy would benefit gastric cancer patients with GOO by accelerating postoperative recovery. For patients with absolute obstruction, no more than 3-day PN therapy is recommended if patients can tolerate general anesthesia and surgery.