Stage Gastric Cancer Patients Research Articles

Fluorescence-Guided Laparoscopy after Oral Hypericin Administration for Staging of Locally Advanced Gastric Cancer-A Pilot Study.

(1) Background: Laparoscopic staging is essential in gastric cancer (GC) to rule out peritoneal metastasis (PM). Hypericin, a plant-derived fluorescent compound, has been suggested to improve laparoscopic visualization of PM from GC. This prospective, single-arm, open-label clinical trial aimed to assess the feasibility and safety of oral hypericin administration as well as the suitability of fluorescence-guided laparoscopy (FGL) for improving the sensitivity and specificity of staging in GC patients (EudraCT-Number: 2015-005277-21; clinicaltrials.gov identifier: NCT-02840331). (2) Methods: GC patients received Laif® 900, an approved hypericin-containing phytopharmaceutical, once orally two to four hours before white light and ultraviolet light laparoscopy. The peritoneal cancer index was evaluated, biopsies taken and hypericin concentrations in serum and peritoneal tissue were determined by mass spectrometry. (3) Results: Between 2017 and 2021, out of 63 patients screened for eligibility, 50 patients were enrolled and treated per protocol. The study intervention was shown to be feasible and safe in all patients. Standard laparoscopy revealed suspicious lesions in 27 patients (54%), among whom 16 (59%) were diagnosed with PM. FGL identified suspicious areas in 25 patients (50%), among whom PM was confirmed in 13 cases (52%). Although hypericin concentrations in serum reached up to 5.64 ng/mL, no hypericin was detectable in peritoneal tissue biopsies. (4) Conclusions: FGL in patients with GC was shown to be feasible but futile in this study. Sufficient levels of hypericin should be ensured in target tissue prior to reassessing FGL with hypericin.

Study on the diagnostic value of MDCT extramural vascular invasion in preoperative N staging of gastric cancer patients

BackgroundTo explore the diagnostic value of multidetector computed tomography (MDCT) extramural vascular invasion (EMVI) in preoperative N Staging of gastric cancer patients.MethodsAccording to the MR-defined EMVI scoring standard of rectal cancer, we developed a 5-point scale scoring system to evaluate the status of CT-detected extramural vascular invasion(ctEMVI), 0–2 points were ctEMVI-negative status, and 3–4 points were positive status for ctEMVI. Patients were divided into ctEMVI positive group and ctEMVI negative group. The correlation between ctEMVI and clinical features was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of ctEMVI for pathological metastatic lymph nodes and N staging, The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of pathological N staging using ctEMVI and short-axis diameter were generated and compared.ResultsThe occurrence rate of lymphovascular invasion (LVI) and proportion of tumors with a greatest diameter > 6 cm in the ctEMVI positive group was higher than that in the ctEMVI negative group (P < 0.05). Spearman correlation analysis showed a positive correlation between ctEMVI and LVI, N stage, and tumor size (P < 0.05). For ctEMVI scores ≥ 3,The AUC of ctEMVI for diagnosing lymph node metastasis, N stage ≥ N2, and N3 stage were 0.857, 0.802, and 0.758, respectively. The sensitivity, NPV and accuracy of ctEMVI for diagnosing N stage ≥ N2 were superior to those of short-axis diameter (P < 0.05), while sensitivity, specificity, PPV, NPV, and accuracy of ctEMVI for diagnosing N3 stage were superior to those of short-axis diameter (P < 0.05).ConclusionctEMVI has important value in diagnosing metastatic lymph nodes and advanced N staging. As an important imaging marker, ctEMVI can be included in the preoperative imaging evaluation of patients, providing important assistance for clinical guidance and treatment.

Expression and clinical significance of ECHS1 in gastric cancer.

Background: Gastric cancer (GC), as one of the most common malignant tumors and the 3rd primary cause of death by cancer globally, poses a great threat to public health. Despite many advancements have been achieved in current treatment avenues for GC, the 5-year survival rates of GC patients remain substandard. Short-chain enoyl-CoA hydratase (ECHS1) exerts pro- or anti-cancer activities in different cancer backgrounds. However, its clinical significance and biological role in GC remain vague and need further investigation. Methods: The expression of ECHS1 in GC tumors and adjacent normal tissues was examined using the GEPIA platform and clinical samples. The effects of ECHS1 on GC cell proliferation and migration were evaluated using colony formation and transwell migration assays. Results: ECHS1 was upregulated in GC tumor tissues in both mRNA and protein levels and increased ECHS1 was markedly linked with tumor location, depth of tumor invasion, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage of GC patients. High ECHS1 expression was also linked with a shorter overal survival (OS), first progression (FP) and post progression survival (PPS). Further subgroup analysis showed that OS was significantly shorter in GC patients with high ECHS1 expression compared to those with low ECHS1 expression belonging to tumors with T3 stage, N2 stage or in instestinal Lauren subgroup. In addition, cytological experiments showed that there was higher ECHS1 expression in GC cell lines compared to the normal gastric epithelium (GES-1) cells, and ECHS1 can promote GC cell proliferation and migration in vitro. Conclusion: ECHS1 plays an oncogenic role in GC and might be a promising therapeutic target for GC.

Circulating Gastric Cancer Stem Cells as Blood Screening and Prognosis Factor in Gastric Cancer.

Gastric cancer (GC) is the fourth leading cause of cancer-related death, associated with late diagnosis and treatment resistance. Currently, screening tests for GC are not cost-effective or have low accuracy. Previously, we described an extended phenotype of gastric cancer stem cells (GCSCs; CD24+CD44+CD54+EpCAM+) that is associated with metastasis and tumor stage in GC patients. The goal of the current research is to evaluate the presence of these GCSCs in the peripheral blood of GC patients and healthy volunteers. A total of 73 blood samples were collected from 32 GC patients and 41 healthy volunteers. After peripheral blood mononuclear cell (PBMC) extraction, multiparametric flow cytometry was performed looking for GCSCs. Using clustering data through artificial intelligence (AI), we defined high/low levels of circulating GCSCs (cGCSCs) and proceeded to evaluate its association with clinical and prognostic variables. Finally, a diagnostic test analysis was performed evaluating patients and healthy volunteers. We found that cGCSCs are present in most GC patients with a mean concentration of 0.48%. The AI clustering showed two groups with different cGCSC levels and clinical characteristics. Through statistical analysis, we confirmed the association between cGCSC levels and lymph node metastasis, distant metastasis, and overall survival. The diagnostic test analysis showed sensibility, specificity, and area under the curve (AUC) of 83%, 95%, and 0.911, respectively. Our results suggest that the assessment of cGCSCs CD24+CD44+CD54+EpCAM+ could be a potential noninvasive test, with prognostic value, as well as highly sensitive and specific for screening or diagnosis of GC; however, a larger scale study will be necessary to confirm this.

Clinicopathological and prognostic significance of elevated BTF3 expression in gastric cancer.

The purpose of this paper was to explore the significance of basic transcription factor 3 (BTF3) in the process and clinicopathological parameters of gastric cancer (GC) patients. GC tissues were collected in our hospital to detect the mRNA expression of BTF3 by quantitative real-time polymerase chain reaction (Q-PCR). Western blot analysis was performed to detect the protein expression of BTF3. Kaplan-Meier method and Log-rank analysis were used to analyze the progression-free survival time and overall time of GC patients, while the Chi-square test was used to investigate the association between BTF3 and clinicopathological parameters of GC patients. SiRNA was designed to suppress the expression of BTF3. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and transwell assay were conducted to determine the viability and invasion ability of GC cells. BTF3 was found abnormally up-regulated in GC tissues and cells and was related to the Grade, Lymph node metastasis and stage of GC patients, as well as the poor progression-free survival and overall survival of them. Besides, inhibition of BTF3 in GC cells could trigger the reduction of cell viability and invasion ability. Our results demonstrated that BTF3 played an important role in the process of GC and could be regarded as a new target for the diagnosis and therapy of GC.

Identification of key genes associated with poor prognosis and neoplasm staging in gastric cancer.

Gastric cancer (GC) is highly biologically and genetically heterogeneous disease with poor prognosis. Increasing evidence indicates that biomarkers can serve as prediction and clinical intervention. Therefore, it is vital to identify core molecules and pathways participating in the development of GC. In this study, GSE54129, GSE56807, GSE63089, and GSE118916 were used for identified overlapped 75 DEGs. GO and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed DEGs mainly enriched in biological process about collagen-containing extracellular matrix and collagen metabolic. Next, protein-protein interaction network was built and the hub gene was excavated. Clinicopathological features and prognostic value were also evaluated. Hub genes were shown as below, FN1, COL1A2, COL1A1, COL3A1, COL4A1, COL6A3, COL5A2, SPARC, PDGFRB, COL12A1. Those genes were upregulation in GC and related to the poor prognosis (except COL5A2, P = .73). What is more, high expression indicated worse T stage and tumor, node, metastasis stage in GC patients. Later, the results of 25 GC tumor specimens and 34 normal tissues showed that FN1, COL3A1, COL4A1, SPARC, COL5A2, and COL12A1 were significantly upregulated in cancer samples. Our study systematically explored the core genes and crucial pathways in GC, providing insights into clinical management and individual treatment.

The prognostic role of neutrophil/lymphocyte ratio and monocyte/lymphocyte ratio in advanced stage gastric cancer patients receiving chemotherapy: a single center experience

Objective: Several studies revealed that peripheral blood Neutrophil/Lymphocyte ratio (NLR) and Monocyte/Lymphocyte Ratio (MLR) were prognostic in various cancer types. However, there are no excessive information about the prognostic significance of NLR and MLR in patients with advanced gastric cancer. As a result, we examined whether NLR and/or MLR could be used as a prognostic marker to predict survival outcomes in patients with advanced gastric cancer receiving palliative chemotherapy.&#x0D; &#x0D; Method: We retrospectively analyzed 119 patients with gastric cancer receiving chemotherapy. We evaluated the relationship between potential prognostic factors and overall survival (OS) times using the Kaplan-Meier method and Cox regression survival modelling.&#x0D; &#x0D; Results: The median overall survival of the patients was 6.9 (2.1-41.6) months. In univariate analysis, NLR (p&lt; 0.001), ECOG performance status (p&lt; 0.001), presence of liver metastases (p&lt; 0.001) and presence of peritoneal metastases (p&lt; 0.001) were found to be associated with survival. The multivariate survival model showed the high NLR (HR=1.59, 95% CI 1.6-2.40, p= 0.026), the patients with ECOG performance score 2-3 (HR=2.91, 95% CI 1.60-5.27, p

The ATR inhibitor VE-821 increases the sensitivity of gastric cancer cells to cisplatin

BackgroundChemoresistance is a common event after cancer chemotherapy, including gastric cancer (GC). Cisplatin has been reported to induce the DNA damage response (DDR), thus leading to chemoresistance. VE-821, a specific inhibitor of ATR, has been proven to suppress a variety of solid malignancies effectively. Our study aimed to explore the effect of VE-821 on enhancing the chemical sensitivity to cisplatin and clarify the potential molecular mechanisms. MethodsCell viability and apoptosis of MKN-45 and AGS were measured by CCK8 and flow cytometry assay respectively. Western blotting was used to detect the expression of target proteins. TCGA database was used to analyze the correlation between the ATR expression with the prognosis of GC patients. The viability of GC organoids was detected by Cell Titer Glo (CTG) through luminescence. ResultsCisplatin inhibited the proliferation and induced apoptosis of GC cells with a relatively high IC50 value, and increased the phosphorylation levels of ATR-CHK1 and H2AX. VE-821 achieved the same effects but by downregulating the phosphorylation levels of the ATR-CHK1 pathway. Besides, higher ATR expression in GC tissues was positively correlated with higher pathological stage in GC patients. Interestingly, ATR inhibition reversed cisplatin-induced STAT3 activation and enhanced H2AX levels. Moreover, VE-821 significantly sensitized GC cells to cisplatin, and these two drugs had synergistic effects in GC cell lines, organoids, and in vivo. ConclusionOur results suggested VE-821 sensitized GC cells to cisplatin via reversing DDR activation. And VE-821 treatment may be a promising therapeutic strategy for GC patients with cisplatin resistance.

MSC-NPRA loop drives fatty acid oxidation to promote stemness and chemoresistance of gastric cancer

Cisplatin (CDDP)-based chemotherapy is the preferred treatment strategy for advanced stage gastric cancer (GC) patients. Despite the efficacy of chemotherapy, the development of chemoresistance negatively affects the prognosis of GC and the underlying mechanism remains poorly understood. Accumulated evidence suggests that mesenchymal stem cells (MSCs) play important roles in drug resistance. The chemoresistance and stemness of GC cells were observed by colony formation, CCK-8, sphere formation and flow cytometry assays. Cell lines and animal models were utilized to investigate related functions. Western blot, quantitative real-time PCR (qRT-PCR) and co-immunoprecipitation were used to explore related pathways. The results showed that MSCs improved the stemness and chemoresistance of GC cells and accounted for the poor prognosis of GC. Natriuretic peptide receptor A (NPRA) was upregulated in GC cells cocultured with MSCs and knockdown of NPRA reversed the MSC-induced stemness and chemoresistance. At the same time, MSCs could be recruited to GC by NPRA, which formed a loop. In addition, NPRA facilitated stemness and chemoresistance through fatty acid oxidation (FAO). Mechanistically, NPRA protected Mfn2 against protein degradation and promoted its mitochondrial localization, which consequently improved FAO. Furthermore, inhibition of FAO with etomoxir (ETX) attenuated MSC-induced CDDP resistance in vivo. In conclusion, MSC-induced NPRA promoted stemness and chemoresistance by upregulating Mfn2 and improving FAO. These findings help us understand the role of NPRA in the prognosis and chemotherapy of GC. NPRA may be a promising target to overcome chemoresistance.

Imaging in Gastric Cancer: Current Practice and Future Perspectives

Gastric cancer represents one of the most common oncological causes of death worldwide. In order to treat patients in the best possible way, the staging of gastric cancer should be accurate. In this regard, endoscopy ultrasound (EUS) has been considered the reference standard for tumor (T) and nodal (N) statuses in recent decades. However, thanks to technological improvements, computed tomography (CT) has gained an important role, not only in the assessment of distant metastases (M status) but also in T and N staging. In addition, magnetic resonance imaging (MRI) can contribute to the detection and staging of primary gastric tumors thanks to its excellent soft tissue contrast and multiple imaging sequences without radiation-related risks. In addition, MRI can help with the detection of liver metastases, especially small lesions. Finally, positron emission tomography (PET) is still considered a useful diagnostic tool for the staging of gastric cancer patients, with a focus on nodal metastases and peritoneal carcinomatosis. In addition, it may play a role in the treatment of gastric cancer in the coming years thanks to the introduction of new labeling peptides. This review aims to summarize the most common advantages and pitfalls of EUS, CT, MRI and PET in the TNM staging of gastric cancer patients.

Up-regulated GRB7 protein in gastric cancer cells correlates with clinical properties and increases proliferation and stem cell properties.

It has been reported that GRB7 is closely related to a variety of human solid tumors, but its role in gastric cancer has not been reported yet. The purpose of this study was to investigate the expression level and intracellular effects of GRB7 in human gastric cancer. Real-time fluorescent quantitative PCR and Western blot were used to detect the expression of GRB7 in gastric cancer cell lines. The immunohistochemical staining and SPSS analysis verified the GRB7 protein expression. Stable gastric cancer cell lines, MTT experiments, clone formation experiments, cell cycle flow cytometry experiments, sphere formation experiments and lateral subpopulation cell sorting experiments were conducted to investigate the role of GRB7 in gastric cancer cells. We found that the expression of GRB7 in gastric cancer cell lines was higher than that of the corresponding normal gastric epithelial cells, and correspondingly higher in gastric cancer tissues than its paired adjacent tissues. GRB7 protein was expressed more highly in cancer tissues than in adjacent tissues. GRB7 protein expression levels were positively correlated with the clinical stage of gastric cancer patients, and negatively correlated with the survival prognosis of patients. GSEA analysis of GRB7 mRNA levels in gastric cancer tissues and normal gastric epithelial tissues from public databases showed that GRB7 may affect cell proliferation and related processes of intracellular stem cells. GRB7 can promote the proliferation of gastric cancer cells and is positively related to the self-renewal ability of gastric cancer stem cells. This study shows that GRB7 molecules highly expressed in gastric cancer tissues can promote the proliferation of gastric cancer cells and increase the proportion of gastric cancer stem cells, so it is expected to become a diagnostic molecule or potential therapeutic target for gastric cancer.

Metastatic lymph nodes and prognosis assessed by the number of retrieved lymph nodes in gastric cancer.

The prognostic value of quantitative assessments of the number of retrieved lymph nodes (RLNs) in gastric cancer (GC) patients needs further study. To discuss how to obtain a more accurate count of metastatic lymph nodes (MLNs) based on RLNs in different pT stages and then to evaluate patient prognosis. This study retrospectively analyzed patients who underwent GC radical surgery and D2/D2+ LN dissection at the Cancer Hospital of Harbin Medical University from January 2011 to May 2017. Locally weighted smoothing was used to analyze the relationship between RLNs and the number of MLNs. Restricted cubic splines were used to analyze the relationship between RLNs and hazard ratios (HRs), and X-tile was used to determine the optimal cutoff value for RLNs. Patient survival was analyzed with the Kaplan-Meier method and log-rank test. Finally, HRs and 95% confidence intervals were calculated using Cox proportional hazards models to analyze independent risk factors associated with patient outcomes. A total of 4968 patients were included in the training cohort, and 11154 patients were included in the validation cohort. The smooth curve showed that the number of MLNs increased with an increasing number of RLNs, and a nonlinear relationship between RLNs and HRs was observed. X-tile analysis showed that the optimal number of RLNs for pT1-pT4 stage GC patients was 26, 31, 39, and 45, respectively. A greater number of RLNs can reduce the risk of death in patients with pT1, pT2, and pT4 stage cancers but may not reduce the risk of death in patients with pT3 stage cancer. Multivariate analysis showed that RLNs were an independent risk factor associated with the prognosis of patients with pT1-pT4 stage cancer (P = 0.044, P = 0.037, P = 0.003, P < 0.001). A greater number of RLNs may not benefit the survival of patients with pT3 stage disease but can benefit the survival of patients with pT1, pT2, and pT4 stage disease. For the pT1, pT2, and pT4 stages, it is recommended to retrieve 26, 31 and 45 LNs, respectively.

The predictive potential of contrast-enhanced computed tomography based radiomics in the preoperative staging of cT4 gastric cancer.

The accuracy of preoperative staging is crucial for cT4 stage gastric cancer patients. The aim of this study was to develop the radiomics model and evaluate its predictive potential for differentiating preoperative cT4 stage gastric cancer patients into pT4b and no-pT4b patients. A multicenter retrospective analysis of 704 gastric cancer patients with preoperative contrast-enhanced computed tomography (CE-CT) staging cT4 between January 2008 and December 2021. These patients were divided into the training cohort (478 patients, the Affiliated Hospital of Qingdao University) and validation cohort (226 patients, the Weihai Wendeng District People's Hospital). According to the pathological stage of the tumors, the patients were divided into pT4b or no-pT4b stage. In the training cohort, the clinical and radiomics features were analyzed to construct the clinical model, tri-phase radiomics signatures and nomogram. Two kinds of methods were employed to achieve dimensionality reduction: (I) the least absolute shrinkage and selection operator (LASSO); and (II) the minimum redundancy maximum relevance (mRMR) algorithms. We utilized Logistic regression, support vector machine (SVM), Decision tree and Adaptive boosted tree (AdaBoost) algorithms as the machine learning classifiers. The nomogram was constructed on the clinical characteristics and the Rad-score. The performance of the models was evaluated by receiver operating characteristic (ROC) area under the curve (AUC), Decision Curve Analysis (DCA) curve and calibration curve. The 345 pT4b and 359 no-pT4b stage patients were included in this study. In the validation cohort, the AUC of the clinical model was 0.793 (95% CI: 0.732-0.855). The tri-phase radiomics features combined with the SVM algorithm was the best radiomics signature with an AUC of 0.862 (95% CI: 0.812-0.912). The nomogram was the best predictive model of all with an AUC of 0.893 (95% CI: 0.834-0.927). In the training and validation cohorts, the calibration curves and DCA curves of the nomogram showed satisfactory result. CE-CT-based radiomics nomogram offers good accuracy and stability in differentiating preoperative cT4 stage gastric cancer patients into pT4b and non-pT4b stages, which has a great clinical relevance for selecting the course of treatment for cT4 stage gastric cancer patients.

Detection Rate and Prognosis of Lymph Nodes in Gastric Cancer Using Nano Carbon Combined with In Vitro Anatomical Sorting.

In this study, we are going to investigate the effect of nano carbon combined with ex vitro anatomical sorting on the detection rate of lymph nodes (LNs) in gastric cancer (GC) along with the analysis of the correlation between LNs detection rate and patients' prognosis. The clinical data of patients undergoing radical gastrectomy in Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University from January 2018 to January 2019 were examined retrospectively. According to whether they adopt nano carbon tracing and specimen sorting method, patients were divided into nano carbon and control groups. The respective rate of detection and correlation of total and positive LNs, respectively, clinical treatment, tumor marker level, and long-term prognosis were matched between these groups. At the same time, the effects of the nano carbon tracer on the detection of total and positive LNs were evaluated. In nano carbon group, more LN specimens could be detected, and the number of positive LNs increased significantly. In addition, in patients with different infiltration stages and LN substations, more LNs could be detected in the nano carbon group for examination, and the detection rate of LNs with diameter less than 5 mm was also more. Furthermore, LNs (preferably positive in number) were correlated positively with the attained LNs number. Otherwise, the use of nano carbon suspension could better label LNs in each substation, especially N1 station, and improve micro-LN detection rate. At the same time, the positive metastasis rate in black-stained LNs was higher (31.67% vs. 13.51%). In relation to the clinical prognosis, CEA's level, i.e., CA199 and CA125, in the nano carbon group is controlled more effectively. Their condition was not easy to progress and relapse, and their mortality was further reduced. As a result, nano carbon, coupled with ex vitro anatomical sorting, may considerably enhance the detection rate of total and positive LNs, thereby improving the accuracy of clinical staging in GC patients, which has a good influence on their long-term prognosis.

Prognostic Value of the Pre-Treatment Prognostic Nutritional Index for Patients with Unresectable Locally-Advanced and Advanced Stage Upper Gastrointestinal Tract Cancer

PurposeThe prognostic nutritional index (PNI) is used to distinguish immune-nutritional status. Previous studies have shown that it is significantly associated with patient outcomes for various malignancies. This study aimed to evaluate the prognostic impact of PNI in patients with unresectable locally-advanced and advanced stage upper gastrointestinal tract cancer, including esophageal cancer and gastric cancer.MethodsA retrospective study of 170 unresectable stage III–IV esophageal cancer and gastric cancer patients was conducted from January 2018 to December 2020. In our retrospective analysis, the pretreatment PNI of patients was calculated and analyzed. The Youden index was estimated to select the optimal cut-off value for PNI. Univariate and multivariate flexible parametric proportional hazards models with restricted cubic splines (RCS) were used to identify independent prognostic factors, and the Kaplan–Meier method was used to estimate survival curves.ResultsThe median follow-up period was 5 months (ranging from 0.06 to 36.92 months). We determined 52.9 as the cut-off value by using the maximum Youden index. Subsequently, patients in the testing group were classified into high PNI and low PNI groups. Kaplan–Meier curves showed the low PNI group had significantly poorer overall survival (OS) than the high PNI group. Median OS in the low PNI group was 4.43 months compared with 8.23 months in the high PNI group (HR 2.42, 95% CI 1.33–4.40, p = 0.004). In the univariate analysis, low PNI, ECOG PS 2, and ECOG PS 3–4 were associated with OS. According to multivariate analysis, low PNI was an independent prognostic factor for OS (HR 2.31, 95% CI 1.24–4.29, p = 0.008).ConclusionPretreatment PNI is useful for independent prognosis of unresectable stage III–IV esophageal cancer and gastric cancer in patients.

P-167 Identification of peptides inhibitor clade A member 1 as a novel serum biomarker for gastric cancer and promotes liver metastasis

Approximately 9. 9%～18. 7% of gastric cancer (GC) patients experience liver metastasis (LM) during the course of the disease and is highly associated with poor prognosis. The development of sensitive biomarkers for detecting and predicting liver metastasis is required for a better clinical outcome. Serpin peptidase inhibitor clade A member 1 (SERPINA1) has been studied in several types of cancer; However, their functional in gastric cancer remains unknown. The present study aimed to evaluate SERPINA1 as a novel serum prognostic biomarker for gastric cancer and associated with liver metastasis. A retrospective cohort with 68 surgically resected gastric cancer patients and a prospective cohort with 45 gastric cancer patients with liver metastasis from The Sixth Affiliated Hospital of Sun Yat-sen University were constructed. Immunohistochemistry was performed to evaluate expression of SERPINA1 protein in tissue specimens. Enzyme-linked immunosorbent assays (ELISAs) were used to analyze the serum specimens. Detailed clinicopathological parameters as well as patients' survival were recorded. A nomogram including SERPINA1 expression was also constructed and validated to predict the prognosis of gastric cancer patients. SERPINA1 protein expression was also analyzed by western blot in human GC derived cell lines and a normal epithelial cell line. Functional experiments were performed by overexpression and downregulation of SERPINA1 in GC derived cell lines and a normal epithelial cell line. Serum SERPINA1 expression was obviously increased and associated with tumor stage in gastric cancer patients, and its high expression was significantly related to differentiated phenotype and vessel invasion, as well as liver metastasis. High SERPINA1 expression was significantly associated with hepatic recurrence after curative surgery, and cumulative incidences of hepatic recurrence were significantly greater in patients with high SERPINA1 expression compared with patients with low SERPINA1 expression. High SERPINA1 expression indicated a poor prognosis, and monogram including serum SERPINA1 expression could predict the prognosis of gastric cancer patients effectively. Moreover, serum ITGB6 expression was associated with ITGB6 expression in tumor tissues. On the other hand, SERPINA1 showed differential expression GC cell lines. By using western blotting, wound-healing and invasion assays in cell lines, overexpression of SERPINA1 increased the migration and invasion of gastric cancer cells, whereas knockdown of SERPINA1 decreased these functions. Moreover, SERPINA1 overexpression increased the protein levels of VEGFR2, which is a key regulator of the VEGF signaling pathway. The present study identified that SERPINA1 could serve as a novel serum biomarker for the risk stratification, prognostic prediction of gastric cancer patients and is also related to liver metastasis.

Diagnostic Value of Spiral CT and Magnetic Resonance Imaging Scanning in Gastric Cancer and Precancerous Lesions.

In order to explore the diagnostic value of spiral CT and magnetic resonance imaging scanning in gastric cancer and precancerous lesions, the author selected 56 gastric cancer patients treated in a medical center (group) as the experimental subjects, and all patients underwent MRI, multislice spiral CT scan, and enhanced CT scan two weeks before surgery; at the same time, the gastric cancer staging results of patients were diagnosed according to surgical pathology. All patients were examined under the condition of knowledge and performed breath-holding exercise before examination. The status, location, and extent of tumor lesions were evaluated. In comparison of T staging of gastric cancer patients with magnetic resonance scanning imaging and postoperative pathological examination results, among them, T staging of 3 patients did not match the results of pathological examination, the accuracy rates of T staging on magnetic resonance scanning imaging were T1 = 94.7%, T2 = 87.6%, T3 = 91.2%, and T4 = 94.7%, and the total accuracy was 92.1%. Comparison of helical CT scan imaging and postoperative pathological examination results is as follows. Among them, T staging of 8 patients did not match the results of pathological examination, 3 patients were ulcerative, 5 were protuberance, the accuracy rates of T staging in spiral CT scan imaging were T1 = 90.8%, T2 = 82.2%, T3 = 76.9%, and T4 = 87.6%, and the total accuracy was 84.5%. The total accuracy rate of imaging N staging was 77.5%, and the total accuracy rate of spiral CT scanning imaging N staging was 80.8%. The accuracy rates of M0 and M1 staging in magnetic resonance imaging were 100.0% and 96.5%, respectively, and the accuracy rates of M0 and M1 staging in spiral CT scan imaging were 96.5% and 96.5%, respectively. The accuracy rate of magnetic resonance imaging for the diagnosis of gastric cancer N staging was 77.4%, and the reason for the low accuracy rate was mainly because the enhancement effect was not obvious due to insufficient enhancement. The accuracy rate of spiral CT in diagnosing N staging of gastric cancer was 80.9%, which was mainly due to the small diameter of the middle celiac artery lymph nodes. Magnetic resonance and spiral CT scans have high value in the early diagnosis and staging of gastric cancer.

62: WHICH GASTRIC CANCER PATIENTS COULD BENEFIT FROM STAGING LAPAROSCOPY? A GIRCG MULTICENTER COHORT STUDY

Abstract Background and aim Staging laparoscopy is an important step of the staging of gastric cancer patients, however, its indication are universally accepted by the different guidelines.This study aimed to define those factors which could help in defining the most appropriate use of staging laparoscopy in a western population. Methods A retrospective cohort study was carried out, including 330 (226 cM- and 104 cM+) gastric cancer patients who had undergone staging laparoscopy between 2010–2020 in seven GIRCG centers. A model including easily-accessible clinical, biochemical and pathological markers was constructed to predict the risk of carcinomatosis. ROC curve and decision curve analyses were used to verify its accuracy and net benefit. Results In the cM- population staging laparoscopy could detect 70 cases who had peritoneal carcinomatosis or positive cytology, for a yield of 31.0%. In cM+ patients staging laparoscopy could exclude carcinomatosis in 15 cases. In cM- patients, intestinal type tumors (0.36, 0.14–0.92; P = 0.035), the presence of signet ring cells (2.58, 1.04–6.33; P = 0.039) and cancers of the upper third (3.36, 1.43–7.92; P = 0.005) were associated with the presence of peritoneal carcinomatosis and/or positive cytology. The ROC curve analysis of the model including the three variables showed an AUC of 0.75 (0.66–0.80, P &amp;lt; 0.001). The decision curve analyses showed that the model had a higher net benefit than the treating all strategy between threshold probabilities of 16 and 50%. Conclusion Staging laparoscopy is a useful tool to address the patient with gastric cancer to the most adequate treatment. In cM- patients the assessment of the location of the tumor, the Lauren’s histotype and the presence of signet ring cells may help in providing additional elements in indicating or not the use of staging laparoscopy.

Postoperative anxiety and depression in surgical gastric cancer patients: their longitudinal change, risk factors, and correlation with survival.

Anxiety and depression are important concerns negatively affecting life quality and prognosis in cancer patients. Then, this prospective cohort study aimed to explore the longitudinal change and potential risk factors for postoperative anxiety and depression in surgical gastric cancer patients.A total of 226 surgical gastric cancer patients were consecutively enrolled. The Hospital Anxiety and Depression Scale (HADS) was used to assess the anxiety and depression status at baseline (M0), 12th month (M12), 24th month (M24), and 36th month (M36) after hospital discharge, then the HADS for anxiety (HADS-A) score and HADS for depression (HADS-D) score were calculated. Diseasefree survival (DFS) and overall survival (OS) were evaluated.HADS-A and HADS-D scores were gradually increased from M0 to M36, and their occurrences and grades were also worsened piece by piece. Additionally, older age, female, unemployed before surgery, single/divorced/widowed marry status, poor education duration, diabetes, hyperlipidemia, large tumor size, high TNM stage, and adjuvant chemotherapy were independent risk factors for postoperative anxiety or depression. Regarding survival, DFS and OS appeared to be shorter in anxiety patients compared to nonanxiety patients at M0 but showed no statistical significance. However, DFS and OS were worse in depression patients compared to non-depression patients at M0.In conclusion, postoperative anxiety and depression are gradually worsened, relating to poor prognosis, and their main risk factors include female, single/divorced/widowed marry status, diabetes, hyperlipidemia, large tumor size, and high TNM stage in gastric cancer patients.

Quantification of Tumor Abnormal Proteins in the Diagnosis and Postoperative Prognostic Evaluation of Gastric Cancer.

Background:Abnormal glycosylation of proteins has been identified in almost all types of cancers and is closely related to the cancer progression, metastasis, and survival of cancer patients. This study was to explore the values of serum tumor abnormal protein (TAP), an abnormal glycochain protein, in the diagnosis and prognosis of gastric cancer (GC).Methods:A total of 335 GC patients were included as the study group, and another 335 subjects served as the control group. Tumor abnormal protein expression was compared between the 2 groups. Correlation analysis was used to assess the correlations of TAP with clinicopathological factors. Gastric cancer patients were divided into training set and test set at a ratio of 2:1. Univariate and multivariate Cox regression analyses in training set were used to evaluate the prognostic significance of TAP in GC patients and explore the independent risk factors for overall survival (OS) and disease-free survival (DFS) to establish a prognostic model, followed by testing of the model. According to the median of TAP, 335 GC patients were divided into 2 groups to plot the survival curves of OS and DFS.Results:Tumor abnormal protein expression in the study group was significantly higher than in the control group. Taking the best cut-off value of TAP (110.128 μm2) as the diagnostic criteria for GC, the sensitivity and specificity of TAP were 83.58% and 97.61%, respectively, and the area under the receiver operating characteristics (ROC) curve was 0.935, which was not inferior to computed tomography (CT). Tumor abnormal protein expression was an independent risk factor for OS and DFS. The prognostic predictive value of TAP was better than that of pathological stage in GC patients. The model with TAP was effective in predicting prognosis.Conclusion:Tumor abnormal protein is an effective indicator for early screening and prognostic evaluation of GC and can also assist the clinical diagnosis and treatment of GC.