Evaluation of the tumor-targeting specific imaging and killing effect of a CEA-targeting nanoparticle in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a prevalent digestive malignancy with significant global mortality and morbidity rates. Improving diagnostic capabilities for CRC and investigating novel therapeutic approaches are pressing clinical imperatives. Additionally, carcinoembryonic antigen (CEA) has emerged as a highly promising candidate for both colorectal tumor imaging and treatment. METHODS: A novel active CEA-targeting nanoparticle, CEA(Ab)-MSNs-ICG-Pt, was designed and synthesized, which served as a tumor-specific fluorescence agent to help in CRC near-infrared (NIR) fluorescence imaging. In cell studies, CEA(Ab)-MSNs-ICG-Pt exhibited specific targeting to RKO cells through specific antibody-antigen binding of CEA, resulting in distribution both within and around these cells. The tumor-targeting-specific imaging capabilities of the nanoparticle were determined through in vivo fluorescence imaging experiments. Furthermore, the efficacy of the nanoparticle in delivering chemotherapeutics and its killing effect were evaluated both in vitro and in vivo. RESULTS: The CEA(Ab)-MSNs-ICG-Pt nanoparticle, designed as a novel targeting agent for carcinoembryonic antigen (CEA), exhibited dual functionality as a targeting fluorescent agent. This CEA-targeting nanoparticle showed exceptional efficacy in eradicating CRC cells in comparison to individual treatment modalities. Furthermore, it exhibits exceptional biosafety and biocompatibility properties. CEA(Ab)-MSNs-ICG-Pt exhibits significant promise due to its ability to selectively target tumors through NIR fluorescence imaging and effectively eradicate CRC cells with minimal adverse effects in both laboratory and in vivo environments. CONCLUSION: The favorable characteristics of CEA(Ab)-MSNs-ICG-Pt offer opportunities for its application in chemotherapeutic interventions, tumor-specific NIR fluorescence imaging, and fluorescence-guided surgical procedures.

Drug Efficacy Comparison of pH-Sensitive and Non-pH-Sensitive Taxol Delivery Nanoparticles in Cancer Therapy.

Taxol is one of the most widely used chemotherapeutic agents but is restricted by its poor solubility and severe side effects in clinical practice. To overcome these limitations, pH-sensitive nanoparticles, Acetalated Dextran6k-PEG5k-PLA2k-Taxol (ADPP-PTX), non-pH-sensitive nanoparticles, and Propionic Anhydride modified Dextran6k-PEG5k-PLA2k-Taxol (PDPP-PTX) are developed for the delivery of Taxol. Compared with PDPP-PTX, ADPP-PTX shows higher sensitivity to acid response and greater anti-proliferative effect on cancer cells. In the in vivo study, ADPP-PTX treatment effectively suppresses the growth of tumors, while only half the dose of Taxol is used, which significantly reduces systemic toxicity compared with Taxol and PDPP-PTX.

Enhanced Photodynamic Therapy Synergizing with Inhibition of Tumor Neutrophil Ferroptosis Boosts Anti-PD-1 Therapy of Gastric Cancer.

For tumor treatment, the ultimate goal in tumor therapy is to eliminate the primary tumor, manage potential metastases, and trigger an antitumor immune response, resulting in the complete clearance of all malignant cells. Tumor microenvironment (TME) refers to the local biological environment of solid tumors and has increasingly become an attractive target for cancer therapy. Neutrophils within TME of gastric cancer (GC) spontaneously undergo ferroptosis, and this process releases oxidized lipids that limit T cell activity. Enhanced photodynamic therapy (PDT) mediated by di-iodinated IR780 (Icy7) significantly increases the production of reactive oxygen species (ROS). Meanwhile, neutrophil ferroptosis can be triggered by increased ROS generation in the TME. In this study, a liposome encapsulating both ferroptosis inhibitor Liproxstatin-1 and modified photosensitizer Icy7, denoted LLI, significantly inhibits tumor growth of GC. LLI internalizes into MFC cells to generate ROS causing immunogenic cell death (ICD). Simultaneously, liposome-deliver Liproxstatin-1 effectively inhibits the ferroptosis of tumor neutrophils. LLI-based immunogenic PDT and neutrophil-targeting immunotherapy synergistically boost the anti-PD-1 treatment to elicit potent TME and systemic antitumor immune response with abscopal effects. In conclusion, LLI holds great potential for GC immunotherapy.

Risk factors of additional surgery after non-curative endoscopic submucosal dissection for early gastric cancer.

BACKGROUND: The criteria for surgical intervention after non-curative endoscopic submucosal dissection (ESD) of early gastric cancer are unclear. We aimed to clarify the risk factors for residual cancer and lymph node metastasis after non-curative ESD and to identify recommendations for additional surgery. METHODS: We collected data on 133 consecutive patients who underwent additional surgery after non-curative ESD of early gastric cancer at Nanjing Drum Tower Hospital from January 2013 to July 2022. Univariate and multivariate analyses were performed to seek risk factors of residual cancer and lymph node metastasis. RESULTS: The incidence rates of residual cancer and lymph node metastasis were 13.5% (18/133) and 10.5% (14/133), respectively. There was neither residual tumor nor lymph node metastasis in 104 (78.2%) cases. Multivariate analyses elucidated that horizontal margin was an independent risk factor for local residual cancer, whereas lymphatic infiltration was an independent risk factor for lymph node metastasis. Patients with mixed histological types were more likely to suffer lymph node metastasis and further undergo additional surgery after non-curative ESD than pure histological type. CONCLUSIONS: Additional gastrectomy with lymph node dissection was strongly recommended in patients with lymphatic infiltration after non-curative ESD of early gastric cancer. Patients with mixed histological type have a high propensity for lymph node metastasis and should be treated as a separate subtype.

Dual tracer navigation for lymph node dissection in laparoscopic radical gastrectomy (DANCE trial): a protocol for a prospective, randomized clinical trial.

BACKGROUND: Lymph node (LN) metastasis is the most common metastasis route in gastric cancer. Extensive dissection of LNs can significantly improve the prognosis of patients with gastric cancer. Recently, multiple clinical studies have demonstrated that either indocyanine green (ICG) or carbon nanoparticles (CNs) can assist to promote the dissection of LNs during laparoscopic radical gastrectomy. Considering the pros and cons of the two tracers, this study proposed a novel method of dual tracer (ICG combined with CNs) for lymphatic tracing in laparoscopic gastric cancer surgery. METHODS: This trial is a prospective, randomized controlled trial (RCT) with an estimation of 516 participants that randomize into 4 groups (1:1:1:1), namely control group, ICG group, CNs group, and dual tracer group. The primary outcome is the number of dissected LNs. The secondary outcomes include positive rate, false positive rate, negative rate, false negative rate, number of metastatic LNs, relationship between LN metastasis and tracer stained, operation duration, blood loss, incision length, morbidity and mortality rate, 3-year DFS (disease free survival), PFS (progression-free survival), and OS (overall survival). DISCUSSION: This study will investigate the efficacy and safety of a novel strategy using dual tracers for laparoscopic gastrectomy. The protocol has been approved by the Ethics Committee of Nanjing Drum Tower Hospital (2021-361-02). The trial findings will be published in peer-reviewed journals. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100051309). Registered 18 September 2021, https://www.chictr.org.cn/showproj.html?proj=133764 .

Subserosal Indocyanine Green Plus Submucosal Carbon Nanoparticle Navigated Laparoscopic Gastrectomy (DANCE-01): a Cohort Study.

BACKGROUND: Indocyanine green (ICG) and carbon nanoparticle (CN) have been widely used for radical gastrectomy. However, synchronous application of ICG and CN in gastrectomy has not been tried yet. For the first time, we herein reported a novel strategy using dual tracers in laparoscopic radical gastrectomy. METHODS: This is a single-center, single-armed, prospective study. For each qualified patient, submucosal CN was injected the day before surgery, and subserosal ICG was injected immediately before surgery. Standard D2 laparoscopic gastrectomy and lymph node examination were subsequently performed. Demographics, lymph nodes (LNs) and postoperative outcome were collected for analysis. To analyze the safety and efficacy of this novel strategy, two contemporary historic control groups using single tracer were established. RESULTS: A total of 60 patients underwent dual tracer laparoscopic gastrectomy and were divided into distal (n = 41) and total (n = 19) groups. An average of 53.3 and 62.2 LNs was harvested from two groups, respectively. The average operation duration was 213.3 and 250.0 min, and intra-operative blood loss was 100.2 ml and 94.7 ml. None received combined organ resection. Margin negativity and R0 resection were achieved in all patients. Three (7.3%) complications occurred in distal group. None required second operation or deceased. Postoperative hospitalization was 9.7 and 9.6 days, respectively. Compared to single tracer, more LNs (p < 0.01), shorter operation time (p < 0.01), less blood lost (p < 0.01) and accelerated postoperative recovery (p < 0.01) were observed in dual tracer group. CONCLUSIONS: We propose a novel, feasible and safe tracing strategy for laparoscopic gastrectomy. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100051309).

Tissue specific imprinting on innate lymphoid cells during homeostasis and disease process revealed by integrative inference of single-cell transcriptomics.

Introduction: Innate lymphoid cells (ILCs) are key components of the immune system, yet the similarity and distinction of the properties across tissues under homeostasis, inflammation and tumor process remain elusive. Methods: Here we performed integrative inference of ILCs to reveal their transcriptional profiles and heterogeneity from single-cell genomics. We collected a large number of ILCs from human six different tissues which can represent unique immune niches (circulation, lymphoid tissue, normal and inflamed mucosa, tumor microenvironment), to systematically address the transcriptional imprinting. Results: ILCs are profoundly imprinted by their organ of residence, and tissue-specific distinctions are apparent under pathological conditions. In the hepatocellular carcinoma microenvironment, we identified intermediate c-kit+ ILC2 population, and lin-CD127- NK-like cells that expressed markers of cytotoxicity including CCL5 and IFNG. Additionally, CD127+CD94+ ILC1s were preferentially enriched in inflamed ileum from patients with Crohn's disease. Discussion: These analyses depicted a comprehensive characterization of ILC anatomical distribution and subset heterogeneity, and provided a base line for future temporal or spatial studies focused on tissue-specific ILC-mediated immunity.

Mixed Histologic Type is a Risk Factor for Lymph Node Metastasis in Submucosal Invasive Early Gastric Cancer.

INTRODUCTION: The treatment regimen for early gastric cancer (EGC) with mixed histologic type remains controversial. We aimed to clarify the relationship between mixed histologic type and lymph node metastasis (LNM) in EGC, with emphasis on submucosal invasive EGC. METHODS: We collected data on 730 consecutive EGC patients at Nanjing Drum Tower hospital between June 2010 and May 2019. Risk factors of LNM and overall survival were analyzed to compare the prognostic differences between different histologic types. RESULTS: Mixed-type EGC patients had higher LNM rates than differentiated-type patients (29.2 % versus 10.6 %, P < 0.001), while no significant difference was found between mixed-type and undifferentiated-type EGC patients (29.2% versus 24.0%, P = 0.225). Multivariate analyses identified tumor location (cardiac and bottom versus antrum), larger tumor size, submucosal invasion, histologic differentiation (undifferentiated-type, mixed-type versus differentiated-type), and lymphovascular invasion as independent risk factors for LNM in EGC patients. Subgroup analysis further elucidated that mixed histologic type was associated with LNM in submucosa invasive EGC, but not in mucosa-confined EGC. There was no statistical significance in overall survival and disease-specific survival of submucosal invasive EGC patients who underwent radical gastrectomy with lymphadenectomy between different histologic types (P = 0.151). CONCLUSIONS: Mixed histologic type may be an independent risk factor for LNM in submucosal invasive EGC. Curative resection with lymphadenectomy should be considered the appropriate treatment for submucosal invasive EGC with mixed histologic type.

Tracers in Gastric Cancer Surgery.

The treatment of gastric cancer mainly depends on radical gastrectomy. Determination of appropriate surgical margins and adequate lymph node (LN) resection are two major surgical steps that directly correlate with prognosis in gastric cancer. Due to the expanding use of minimally invasive procedures, it is no longer possible to locate tumors and LNs through touch. As an alternative, tracers have begun to enter the field due to their capacities for intraoperative visualization. Herein, we summarize the application of contemporary tracers in gastric cancer surgery, including isosulfan blue, methylene blue, patent blue, indocyanine green, carbon particles, and radioactive tracers. Their mechanisms, administration methods, detection efficiency, and challenges, as well as perspectives on them, are also outlined.

Comparison of short-term outcomes between robotic-assisted and laparoscopic gastrectomy guided by carbon nanoparticle suspension injection in gastric cancer.

BACKGROUND: The clinical application of robotic-assisted gastrectomy remains controversial, especially as clinical studies of this operation navigated by carbon nanoparticle suspension injection (CNSI) have not been conducted. This study aims to assess the perioperative safety and efficacy of CNSI-guided robotic-assisted gastrectomy in patients with gastric cancer by focusing on short-term outcomes. METHODS: A retrospective analysis of patients who underwent CNSI-guided laparoscopic or robotic-assisted gastrectomy with a pathological diagnosis of gastric cancer was conducted. Data on demographics, surgical management, clinical-pathological results and short-term outcomes were compared among the groups. RESULTS: A total of 126 eligible patients were separated into the robotic-assisted gastrectomy (RAG) group (n = 16) and the laparoscopic gastrectomy (LG) group (n = 110) in total. The operation time of the RAG group is longer than the LG group (p = 0.0000). When it comes to perioperative and short-term complications, there exists no statistical difference between the two groups. CONCLUSION: The time required for CNSI-guided robotic-assisted gastrectomy is longer than that for CNSI-guided laparoscopic gastrectomy. CNSI-guided robotic-assisted gastrectomy is safe and effective.

Oxygen tank for synergistic hypoxia relief to enhance mitochondria-targeted photodynamic therapy.

BACKGROUND: Mitochondria play an essential role in cellular redox homeostasis maintenance and meanwhile serve as an important target for organelle targeted therapy. Photodynamic therapy (PDT) is a promising strategy for organelle targeted therapy with noninvasive nature and highly spatiotemporal selectivity. However, the efficacy of PDT is not fully achieved due to tumor hypoxia. Moreover, aerobic respiration constantly consumes oxygen and leads to a lower oxygen concentration in mitochondria, which continuously limited the therapeutic effects of PDT. The lack of organelle specific oxygen delivery method remains a main challenge. METHODS: Herein, an Oxygen Tank is developed to achieve the organelle targeted synergistic hypoxia reversal strategy, which not only act as an oxygen storage tank to open sources and reduce expenditure, but also coated with red blood cell membrane like the tank with stealth coating. Within the oxygen tank, a mitochondrion targeted photosensitizer (IR780) and a mitochondria respiration inhibitor (atovaquone, ATO) are co-loaded in the RBC membrane (RBCm) coated perfluorocarbon (PFC) liposome core. RESULTS: Inside these bio-mimic nanoparticles, ATO effectively inhibits mitochondrial respiration and economized endogenous oxygen consumption, while PFC supplied high-capacity exogenous oxygen. These Oxygen modulators reverse the hypoxia status in vitro and in vivo, and exhibited a superior anti-tumor activity by mitochondria targeted PDT via IR780. Ultimately, the anti-tumor effects towards gastric cancer and colon cancer are elicited in vivo. CONCLUSIONS: This oxygen tank both increases exogeneous oxygen supply and decreases endogenous oxygen consumption, may offer a novel solution for organelle targeted therapies.

Glucose Metabolism Intervention-Facilitated Nanomedicine Therapy.

Ordinarily, cancer cells possess features of abnormally increased nutrient intake and metabolic pathways. The disorder of glucose metabolism is the most important among them. Therefore, starvation therapy targeting glucose metabolism specifically, which results in metabolic disorders, restricted synthesis, and inhibition of tumor growth, has been developed for cancer therapy. However, issues such as inadequate targeting effectiveness and drug tolerance impede their clinical transformation. In recent years, nanomaterial-assisted starvation treatment has made significant progress in addressing these challenges, whether as a monotherapy or in combination with other medications. Herein, representative researches on the construction of nanosystems conducting starvation therapy are introduced. Elaborate designs and interactions between different treatment mechanisms are meticulously mentioned. Not only are traditional treatments based on glucose oxidase involved, but also newly sprung small molecule agents targeting glucose metabolism. The obstacles and potential for advancing these anticancer therapies were also highlighted in this review.

Risk Factor and Surgical Outcome of Petersen's Hernia After Gastrectomy in Gastric Cancer.

BACKGROUND: Petersen's hernia is a life-threatening complication after gastrectomy. This study is dedicated to identify risk factors for Petersen's hernia and compare clinical outcomes between patients receiving early or delayed surgical interventions. METHODS: Data from all patients who received gastrectomy due to gastric cancer were collected. Clinical characteristics were compared between Petersen and non-Petersen groups, bowel necrosis and non-necrotic groups. Propensity score matching (PSM) was conducted to generate two comparative groups. Univariate analysis and multivariate logistic regression were performed for risk factor evaluation. RESULTS: A total of 24 cases of Petersen's hernia were identified from 1,481 cases of gastrectomy. PSM demonstrated that lower body mass index [BMI; odds ratio (OR) = 0.2, p < 0.01] and distal gastrectomy (OR = 6.2, p = 0.011) were risk factors for Petersen's hernia. Longer time interval from emergence visit to laparotomy (p = 0.042) and elevated preoperative procalcitonin (p = 0.033) and C-reactive protein (CRP; p = 0.012) were associated with higher risk of bowel necrosis in Petersen's hernia. Early surgical intervention resulted in less bowel necrosis rate (p = 0.012) and shorter length of necrotic bowel (p = 0.0041). CONCLUSIONS: Low BMI and distal gastrectomy are independent risk factor for Petersen's hernia after gastrectomy. Curtailing observing time and executing prompt surgery are associated with bowel viability and better outcome in patients with Petersen's hernia.

Novel CircRNAs in Hub ceRNA Axis Regulate Gastric Cancer Prognosis and Microenvironment.

Gastric cancer (GC) is one of the most prevalent malignancies with an unfavorable survival rate. Immunotherapy may contribute to a better prognosis. However, several phase III trials failed. Circular RNA (circRNA) is a novel type of non-coding RNA, plays a vital role in the progression of tumors. The expression and function of circRNA in the GC immune microenvironment remain obscure. In this study, we utilized a bioinformatic analysis to construct a circRNA/microRNA (miRNA)/messenger RNA (mRNA) network involved in the progression and prognosis of GC. CircRNA DYRK1A_017, circRNA FLNA_118, miR-6512-3p, miR-6270-5p, and VCAN were identified as the key molecules in the hub regulatory axis. Dysregulation of this axis contributed to the cancer-associated signaling pathways (epithelial-mesenchymal transition [EMT], Nuclear factor kappa ß-Tumor necrosis factor-α (NFκß-TNFα) signaling, and angiogenesis) and aberrant immune microenvironment (infiltration by tumor associated macrophage, regulatory T cell, and mast cell). More importantly, the immunosuppressive tumor microenvironment may reveal the mechanism of novel circRNAs in tumors and serve as the target of immunotherapy.

The short-term and long-term outcomes of indocyanine green tracer-guided laparoscopic radical gastrectomy in patients with gastric cancer.

BACKGROUND: The safety and efficacy of indocyanine green (ICG) imaging navigational laparoscopic gastrectomy remain controversial. This study is to evaluate the short-term and long-term outcomes of ICG-guided laparoscopic radial gastrectomy in patients with gastric cancer. METHODS: Consecutive patients with definitive diagnosis of gastric cancer that underwent laparoscopic radical gastrectomy were collected retrospectively. Propensity score matching (PSM) at 1:1 ratio was performed to compare the outcomes of two groups. RESULTS: A total of 122 qualified patients were divided into ICG group (n = 34) and non-ICG group (n = 88). PSM yielded 28 patients with comparable baseline characteristics into each group. The number of retrieved lymph node in ICG group was significantly higher than that in non-ICG group (P = 0.0196). There was no statistical difference of perioperative, short-term, and long-term complications between the two groups. CONCLUSION: ICG-guided laparoscopic radical gastrectomy is safe and effective, and ICG-navigated lymphadenectomy improves the number of retrieved lymph nodes for patients with gastric cancer.

Comparative short-term and long-term outcomes between internal and external intestinal plication in the management of small bowel obstruction.

BACKGROUND: Small bowel obstruction (SBO) is common and usually requires surgical intervention. Intestinal plication is a traditional but critical strategy for SBO in certain scenarios. This study is to compare the short-term and long-term outcome between internal and external plications in the management of SBO. METHODS: All patients receiving intestinal plication in our hospital were retrospectively collected. Short-term outcome including postoperative complications, reoperation, postoperative ICU stay, starting day of liquid diet and postoperative hospitalization, as well as long-term outcome including recurrence of obstruction, readmission, reoperation and death were compared between groups. Gut function at annual follow-up visits was evaluated as well. RESULTS: Nine internal and 11 external candidates were recruited into each group. The major causes of plication were adhesive obstruction, abdominal cocoon, volvulus and intussusception. Lower incidence of postoperative complication (p = 0.043) and shorter postoperative hospitalization (p = 0.049) was observed in internal group. One patient receiving external plication died from anastomosis leakage. During the 5-year follow-up period, the readmission rate was low in both groups (22.2 % vs. 9.1 %), and none of patients required reoperation or deceased. None of patients exhibited gut dysfunction, and all patients restored normal gut function after 4 years. Patients in external group demonstrated accelerated recovery of gut function after surgery. CONCLUSIONS: This study compares short-term and long-term outcome of patients receiving internal or external intestinal plication. We suggest a conservative attitude toward external plication strategy. Surgical indication for intestinal plication is critical and awaits future investigations.

Risk factors for lymph node metastasis in gastric neuroendocrine tumor: a retrospective study.

BACKGROUND: Lymph node metastasis (LNM) plays a vital role in the determination of clinical outcomes in patients with gastric neuroendocrine tumor (G-NET). Preoperative identification of LNM is helpful for intraoperative lymphadenectomy. This study aims to investigate risk factors for LNM in patients with G-NET. METHODS: We performed a retrospective study involving 37 patients in non-LNM group and 82 patients in LNM group. Data of demographics, preoperative lab results, clinical-pathological results, surgical management, and postoperative situation were compared between groups. Significant parameters were subsequently entered into logistic regression for further analysis. RESULTS: Patients in LNM group exhibited older age (p = 0.011), lower preoperative albumin (ALB) (p = 0.003), higher carcinoembryonic antigen (CEA) (p = 0.020), higher International normalized ratio (p = 0.034), longer thrombin time (p = 0.018), different tumor location (p = 0.005), higher chromogranin A positive rate (p = 0.045), and higher Ki-67 expression level (p = 0.002). Logistic regression revealed ALB (p = 0.043), CEA (p = 0.032), tumor location (p = 0.013) and Ki-67 (p = 0.041) were independent risk factors for LNM in G-NET patients. CONCLUSIONS: ALB, CEA, tumor location, and Ki-67 expression level correlate with the risk of LNM in patients with G-NET.

Controlling Nutritional Status (CONUT) score as a predictive marker for short-term complications following gastrectomy of gastric cancer: a retrospective study.

BACKGROUND: It is well established that the controlling nutritional status (CONUT) score was correlated with long-term outcomes in gastric cancer (GC), but the significance of CONUT for postoperative short-term outcomes remains unclear. The study aimed to characterize the relationship between CONUT and short-term complications following gastrectomy of GC. METHODS: We collected data on 1479 consecutive GC patients at Nanjing Drum Tower Hospital between January 2016 and December 2018. Univariate and multivariate analyses of predictive factors for postoperative complications were performed. The cutoff value of the CONUT score was determined by Youden index. RESULTS: Among all of the patients, 431 (29.3%) patients encountered postoperative complications. Multivariate analyses identified CONUT was an independent predictor for postoperative short-term complications (OR 1.156; 95% CI 1.077-1.240; P < 0.001). Subgroup analysis elucidated that CONUT was related to postoperative complications both in early gastric cancer and advanced gastric cancer. We further explored that patients with high CONUT score had prolonged hospital stay (12.3 ± 6.0 vs 11.1 ± 4.6, P < 0.001) and more total hospital charges (7.6 ± 2.4 vs 7.1 ± 1.6, P < 0.001). CONCLUSIONS: The present study demonstrated that the preoperative CONUT was an independent predictor for short-term complications following gastrectomy of GC.

Identification of hub genes in gastric cancer by integrated bioinformatics analysis.

BACKGROUND: Gastric cancer (GC) is one of the most common cancer worldwide. With the high rates of metastasis and recurrence, its overall survival remains poor at the present time. Hence, seeking new potential therapeutic targets of GC is important and urgent. METHODS: We retrieved the gene expression profiles and clinical data from The Cancer Genome Atlas (TCGA) datasets. After screening differentially expressed genes (DEGs), we carried out the survival analysis for overall survival to pick out robust DEGs. To explore the role of these robust DEGs, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Subsequently, protein interactions network was constructed utilizing the Search Tool for the Retrieval of Interacting Genes (STRING) database. We then presented the module analysis and filtered out hub genes by the Cytoscape software. Finally, Kaplan-Meier analysis was utilized to demonstrate the prognostic role of these hub genes. RESULTS: According to the gene expression profiles of TCGA and the survival analysis, 238 robust DEGs were filtered out, consisting of 140 up-regulated and 98 down-regulated genes. The up-regulated DEGs were mainly enriched in systemic lupus erythematosus, cytokine activity, and alcoholism, while down-regulated DEGs were mainly enriched in steroid hormone receptor activity, immune response, and metabolism. Through the construction of the protein-protein interaction (PPI) network, eight hub genes were finally screened out, including CCR8, HIST1H3B, HIST1H2AH, HIST1H2AJ, NPY, HIST2H2BF, GNG7, and CCL25. CONCLUSIONS: Our study picked out eight hub genes, which might be potential prognostic biomarkers for GC and even be treatment targets for clinical implication in the future.