Xiangyu Meng

Background: Emerging research indicates connections between endoplasmic reticulum (ER) stress and gastric cancer (GC), but related genetic factors remain unclear. This study is aimed at prioritizing ER stress‐related genes associated with GC risk using multiomics data. Methods: We integrated GC GWAS data from FinnGen (discovery) and United Kingdom Biobank (replication) cohorts with QTL datasets, including mQTLs, eQTLs, and pQTLs. Summary‐data‐based Mendelian randomization (SMR) and colocalization analyses were performed to prioritize candidate genes, followed by characterization using transcriptomic profiling (GSE118916), methylation‐expression correlation analysis (TCGA‐STAD), and single‐cell RNA‐seq analysis (GSE270680). Results: SMR analyses identified 83 mQTL, 10 eQTL, and 2 pQTL signals associated with GC risk. Among these, colocalization evidence was observed for 47 mQTL, 5 eQTL, and 2 pQTL signals. Transcriptomic analysis showed that PCSK6 , YOD1 , and RNF5 exhibited expression changes directionally consistent with their SMR associations with GC risk, whereas CTNNBIP1 showed an inconsistent expression pattern. PCSK6 was supported by mQTL, eQTL, and mQTL‐eQTL evidence but lacked colocalization. YOD1 , identified through pQTL‐SMR, showed strong colocalization evidence (PPH4 = 0.95). RNF5 was highlighted via eQTL‐SMR but lacked colocalization support. CTNNBIP1 was supported by mQTL, eQTL, and mQTL‐eQTL evidence and colocalization, with a significant methylation‐expression correlation observed in TCGA‐STAD. Single‐cell RNA‐seq revealed that PCSK6 was predominantly expressed in fibroblasts, YOD1 in epithelial cells and mast cells, and RNF5 broadly across fibroblasts, epithelial cells, and selected immune cells. Conclusions: This multiomics study prioritized PCSK6 , YOD1 , and RNF5 as ER stress‐related candidate genes showing genetic associations with GC risk and directionally consistent expression patterns, with single‐cell analysis indicating distinct cell‐type‐specific expression patterns. These findings offer useful context for future functional and mechanistic investigations of the prioritized candidate genes.

Low temperature plasma (LTP), as an emerging cancer treatment technology, has shown significant therapeutic potential due to its unique physical and chemical properties and biological effects. This article reviews the basic characteristics of LTP and its multiple mechanisms of application in tumor treatment. LTP can induce various cell death modes, including apoptosis, pyroptosis, and autophagy, through its unique chemical and physical properties. Additionally, studies have demonstrated that the combination of LTP with traditional chemotherapy drugs (such as cisplatin and paclitaxel) can enhance the anti-tumor efficacy of the drugs while reducing drug resistance. The combined application of LTP and nanomaterials also shows promising prospects. However, LTP still faces some challenges and limitations in medical applications. Future research needs to further explore the specific applications of LTP in different tumor types, optimize treatment plans, and develop more portable and efficient LTP devices to promote its application in clinical treatment.

Gastric cancer (GC) ranks as the third most prevalent malignancy and a leading cause of cancer-related mortality worldwide. However, the majority of patients with GC are diagnosed at an advanced stage, highlighting the urgent need for effective perioperative and postoperative chemotherapy to prevent relapse and metastasis. The current treatment strategies have limited overall efficacy because of intrinsic or acquired drug resistance. Recent evidence suggests that dysregulated long non-coding RNAs (lncRNAs) play a significant role in mediating drug resistance in GC. Therefore, there is an imperative to explore novel molecular mechanisms underlying drug resistance in order to overcome this challenging issue. With advancements in deep transcriptome sequencing technology, lncRNAs—once considered transcriptional noise—have garnered widespread attention as potential regulators of carcinogenesis, including tumor cell proliferation, metastasis, and sensitivity to chemo- or radiotherapy through multiple regulatory mechanisms. In light of these findings, we aim to review the mechanisms by which lncRNAs contribute to drug therapy resistance in GC with the goal of providing new insights and breakthroughs toward overcoming this formidable obstacle.

Introduction The Pfannenstiel incision is often used in gynecological Cesarean section; however, there is limited research on the use of the Pfannenstiel incision for specimen extraction in laparoscopic surgery for the treatment of colorectal cancer. Aim To evaluate the safety of using the...

Background: Hypoxia and inflammation tumor microenvironment (TME) play a crucial role in tumor development and progression. Although increased understanding of TME contributed to gastric cancer (GC) progression and prognosis, the direct interaction between macrophage and GC cells was not fully understood. Methods: Hypoxia and normoxia macrophage microarrays of GEO database was analyzed. The peripheral blood mononuclear cell acquired from the healthy volunteers. The expression of C-X-C Motif Chemokine Ligand 8 (CXCL8) in GC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR), western-blot, Elisa and immunofluorescence. Cell proliferation, migration, and invasion were evaluated by cell counting kit 8 (CCK8), colony formation, real-time imaging of cell migration and transwell. Flow Cytometers was applied to identify the source of cytokines. Luciferase reporter assays and chromatin immunoprecipitation were used to identify the interaction between transcription factor and target gene. Especially, a series of truncated and mutation reporter genes were applied to identify precise binding sites. The corresponding functions were verified in the complementation test and in vivo animal experiment. Results: Our results revealed that hypoxia triggered macrophage secreted CXCL8, which induced GC invasion and proliferation. This macrophage-induced GC progression was CXCL8 activated C-X-C Motif Chemokine Receptor 1/2 (CXCR1/2) on the GC cell membrane subsequently hyperactivated Janus kinase 1/ Signal transducer and activator of transcription 1 (JAK/STAT1) signaling pathway. Then, the transcription factor STAT1 directly led to the overexpression and secretion of Interleukin 10 (IL-10). Correspondingly, IL-10 induced the M2-type polarization of macrophages and continued to increase the expression and secretion of CXCL8. It suggested a positive feedback loop between macrophage and GC. In clinical GC samples, increased CXCL8 predicted a patient’s pessimistic outcome. Conclusion: Our work identified a positive feedback loop governing cancer cells and macrophage in GC that contributed to tumor progression and patient outcome.

Gastric cancer (GC) is a common malignant solid tumor that is characterized by high hypoxia. The transcription of genes associated with hypoxia affects tumor occurrence and development. Long non-coding RNAs (lncRNAs) have been reported to play important roles in cancer development. In this study, we screened for differentially expressed ncRNAs (non-coding RNA) and mRNAs between hypoxia-inducible factor-1 (HIF-1α) knockdown GC cells and scrambled GC cells. Microarray data revealed that HIF-1α regulated the expression of LINC01355 (Hypoxia Yield Proliferation Associated LncRNA, HYPAL). HYPAL was found to be significantly upregulated in GC cells and tissues and was correlated with poor GC prognosis. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays revealed that HIF-1α promoted HYPAL expression by binding the promoter region. A regulatory network for the competing endogenous RNA (ceRNA) was constructed using bioinformatics tools. Mechanistic studies revealed that HYPAL acted as a ceRNA of miR-431-5p to regulate CDK14 expression. Carcinogenic effects of HYPAL were evaluated in vitro and in vivo. The HIF-1α/HYPAL/miR-431-5p/CDK14 (Cyclin-dependent kinase 14) axis activated the Wnt/β-catenin signaling pathway and induced GC cell proliferation while inhibiting apoptosis. In conclusion, HYPAL is a potential molecular target for GC therapy.

Background: Totally laparoscopic gastrectomy (TLG) has recently been accepted as a treatment strategy for gastric cancer (GC). Aim: In this study, we conducted a meta-analysis to evaluate the safety and feasibility of TLG compared with laparoscopic-assisted gastrectomy (LAG) in GC. Methods: Feasible studies comparing the TLG and LAG published up to March 2019 were searched online. The data showing short-term and complication outcomes were extracted to be pooled and analyzed. Results: Thirty-four studies, including 7974 patients were eventually eligible. There was no statistically significant difference on operation time between the two groups (weighted mean difference [WMD] = 2.43, 95% confidence interval [CI]: −4.16 to 9.02, P = .47). The time of anvil insertion time was shorter in the TLG group compared with the LAG group (WMD = −1.87, 95% CI: −2.60 to −1.15, P < .01). The TLG was significantly superior to LAG in the comparison of less trauma. In terms of radical resection, the number of lymph nodes obtained by TLG was significantly more than that obtained by LAG (WMD = 2.65, 95% CI: 1.54–3.76, P < .01). The pooled meta-analysis suggested that the patients undergoing TLG had a quicker recovery and less pain. In the advanced gastric cancer gastrectomy, the TLG could receive a longer proximal margin compared with the LAG (WMD = 0.72, 95% CI: 0.48–0.95, P < .01). Regardless of the reconstruction method, the TLG was superior to the LAG in terms of surgical parameters and postoperative recovery. Like the LAG, the TLG was safe and advantageous. A lower risk trend of conversion to open laparotomy was observed in the TLG (relative risk [RR] = 0.72, 95% CI: 0.12–4.38, P = .72). The body mass index >25 kg/m ² patients undergoing totally laparoscopic gastrectomy (TLGA) had a lower risk of overall complications (RR = 0.88, 95% CI: 0.48–1.63, P = .69). The patients with early gastric cancer or Billroth-I anastomosis were suitable to undergo the TLG (a lower risk of anastomotic leakage [RR = 0.01, 95% CI: 0.00–0.23, P < .01] and gastralgia [RR = 0.27, 95% CI: 0.08–0.88, P = .03], respectively). Conclusions: The TLG was a safe and reliable procedure compared with the LAG with reduced trauma, faster recovery, and not more complications.

Background: Gastric cancer (GC) accounts for high mortality. RNA methylation has recently gained interest as markers in specific tumors. This study aimed to uncover the function of the roles of 25 RNA methylation regulators in GC. Methods: RNA sequence and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. “STRING” and R were performed to analyze the correlation among the methylase. COX and LASSO were performed to screen for prognostic associated RNA methylation regulators. A prognostic model was established based on the expression of methylase. RT-PCR and immunohistochemistry detected the expression of methylase in GC cells and tissue. Kaplan–Meier curve and Cox analysis were applied to evaluate the effectiveness of the model. Results: The prediction model was established based on the expression of m6A RNA methylation regulators FTO (fat mass and obesity-associated) and RBM15 (RNA binding motif protein 15). Based on the model, GC patients were divided into “high risk” and “low risk” groups to compare the differences in survival. The model was re-evaluated with the clinical data of our center. Conclusion: The two-methylase combination model was an independent prognostic factor of GC.

Background: To investigate the clinical significance of ubiquitin-specific peptidase 19 (USP19) expression in gastric cancer (GC) compared with that in normal tissues and gastric cell lines. Methods: USP19 protein expression was analyzed in 212 paired GC samples using immunohistochemical staining. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the level of USP19 in gastric cell lines. The biological functions of USP19 were investigated by MTT assay, colony-forming assay, wound healing assay and gelatin zymography, and apoptotic cells were detected by immunohistochemistry assays in SGC7901 xenograft models. Results: USP19 expression was significantly increased in GC cells and tissues, and the high level of USP19 expression was positively correlated with the Lauren’s classification and poor prognosis. Moreover, USP19 was identified as a novel independent prognostic biomarker in GC patients. Enhanced USP19 expression promoted GC cell proliferation and metastasis through reduced cleaved caspase-3 and increased MMP2/MMP9 expression and promoted enzyme activity in the study, and verified the results through The Cancer Genome Atlas (TCGA) and bioinformatic websites from the Kaplan–Meier plotter (http://kmplot.com) and GEPIA (http://gepia2.cancer-pku.cn.). Conclusion: Our study suggests that USP19 promoted tumor progression by inducing MMP2/MMP9 expression and related enzyme activity. Hence, USP19 may be a valuable prognostic predictor for GC, and the USP19-MMP2/MMP9 axis could serve as a therapeutic target.

Objective: The benefit of adjuvant therapy (AT) remains controversial in stage IB gastric cancer (GC). This study aimed to offer a reference for the rational indications of AT. Methods: We retrospectively included 1216 stage IB GC who experienced curative surgery from the SEER database between 2004 and 2015. These patients were allocated into two groups: Group AT and Group surgery alone (Group SA). We established a nomogram to predict OS and then divided whole cohort into low-risk and high-risk groups based on the OS predicted by the nomogram. Results: Six variables, which were significantly related with OS of entire patients after matched, were incorporated in the nomogram. These variables were age, examined lymph nodes, tumor site, marital, family income and stage IB. The C-index of the model was 0.637 and the calibration curve showed that the anticipated values were in accordance with the actual values. The decision curve demonstrated that the optimal clinical impact was achieved when the threshold possibility was 0–56%. Then, the entire cohort was separated into low-risk (≤159 points) as well as high-risk (>159 points) groups based on the projected 5-year OS of recursive partitioning analysis. Group SA revealed a significantly poorer OS than Group AT for high-risk patients (p < .001); on the other hand, there was a comparable OS for low-risk patients (p = .361). Conclusions: We have developed an effective, intuitional and applied prognostic tool to clinical decision-making. For stage IB GC after surgical resection, AT was only recommended for high-risk patients. However, AT may be dispensable for low-risk patients.