Predictive value of machine learning models for lymph node metastasis in gastric cancer: A two-center study

BACKGROUND Gastric cancer is one of the most common malignant tumors in the digestive system,ranking sixth in incidence and fourth in mortality worldwide.Since 42.5%of metastatic lymph nodes in gastric cancer belong to nodule type and peripheral type,the application of imaging diagnosis is restricted.AIM To establish models for predicting the risk of lymph node metastasis in gastric cancer patients using machine learning(ML)algorithms and to evaluate their pre-dictive performance in clinical practice.METHODS Data of a total of 369 patients who underwent radical gastrectomy at the Depart-ment of General Surgery of Affiliated Hospital of Xuzhou Medical University(Xuzhou,China)from March 2016 to November 2019 were collected and retro-spectively analyzed as the training group.In addition,data of 123 patients who underwent radical gastrectomy at the Department of General Surgery of Jining First People’s Hospital(Jining,China)were collected and analyzed as the verifi-cation group.Seven ML models,including decision tree,random forest,support vector machine(SVM),gradient boosting machine,naive Bayes,neural network,and logistic regression,were developed to evaluate the occurrence of lymph node metastasis in patients with gastric cancer.The ML models were established fo-llowing ten cross-validation iterations using the training dataset,and subsequently,each model was assessed using the test dataset.The models’performance was evaluated by comparing the area under the receiver operating characteristic curve of each model.RESULTS Among the seven ML models,except for SVM,the other ones exhibited higher accuracy and reliability,and the influences of various risk factors on the models are intuitive.CONCLUSION The ML models developed exhibit strong predictive capabilities for lymph node metastasis in gastric cancer,which can aid in personalized clinical diagnosis and treatment.

Nomogram established using risk factors of early gastric cancer for predicting the lymph node metastasis

BACKGROUND For the prognosis of patients with early gastric cancer(EGC),lymph node metastasis(LNM)plays a crucial role.A thorough and precise evaluation of the patient for LNM is now required.AIM To determine the factors influencing LNM and to construct a prediction model of LNM for EGC patients.METHODS Clinical information and pathology data of 2217 EGC patients downloaded from the Surveillance,Epidemiology,and End Results database were collected and analyzed.Based on a 7:3 ratio,1550 people were categorized into training sets and 667 people were assigned to testing sets,randomly.Based on the factors influencing LNM determined by the training sets,the nomogram was drawn and verified.RESULTS Based on multivariate analysis,age at diagnosis,histology type,grade,T-stage,and size were risk factors of LNM for EGC.Besides,nomogram was drawn to predict the risk of LNM for EGC patients.Among the categorical variables,the effect of grade(well,moderate,and poor)was the most significant prognosis factor.For training sets and testing sets,respectively,area under the receiver-operating characteristic curve of nomograms were 0.751[95%confidence interval(CI):0.721-0.782]and 0.786(95%CI:0.742-0.830).In addition,the calibration curves showed that the prediction model of LNM had good consistency.CONCLUSION Age at diagnosis,histology type,grade,T-stage,and tumor size were independent variables for LNM in EGC.Based on the above risk factors,prediction model may offer some guiding implications for the choice of subsequent therapeutic approaches for EGC.

ScRNA-seq reveals the correlation between M2 phenotype of tumorassociated macrophages and lymph node metastasis of breast cancer

The process of lymphatic metastasis was proved to be associated with podoplanin-expressing macrophages in breast cancer(BC).This study aimed to investigate the role of the M2 phenotype of tumor-associated macrophages and mine the key M2 macrophages-related genes for lymph node metastasis in BC.We downloaded the GSE158399 dataset from the Gene Expression Omnibus(GEO)database,which includes transcriptomic profiles of individual cells from primary tumors,negative lymph nodes(NLNs),and positive lymph nodes(PLNs)of breast cancer patients.The cell subsets were identified by clustering analysis after quality control of the scRNA-seq using Seurat.The activation and migration capability of M2 macrophages were evaluated with R package“GSVA”.The key M2 macrophages-related genes were screened from the differential expressed genes(DEGs)and M2 macrophages activation and migration gene sets collected from MSigDB database.Our analysis identified three main cell types in primary tumors,NLNs,and PLNs:basal cells,luminal cells,and immune cell subsets.The further cell type classification of immune cell subsets indicated M2 macrophages accumulation in NLs and PLs.The GSVA enrichment scores for activation and migration capability were increased significantly in M2 macrophages from primary tumors than NLNs and PLNs(pvalue<0.001).Seven M2 macrophages activation-related and 15 M2 macrophages migration-related genes were significantly up-regulated in primary tumors than NLNs and PLNs.The proportion and GSVA enrichment scores for activation and migration of M2 macrophages may be potential markers for lymph node metastasis in breast cancer.Our study demonstrated that twenty-two up-regulated mRNA may be possible therapeutic targets for lymph node metastasis in breast cancer.

Prediction of lymph node metastasis in early gastric signet-ring cell carcinoma:A real-world retrospective cohort study

BACKGROUND Signet-ring cell carcinoma(SRCC)was previously thought to have a worse prognosis than other differentiated gastric cancer(GC),however,recent studies have shown that the prognosis of SRCC is related to pathological type.We hypothesize that patients with SRCC and with different SRCC pathological components have different probability of lymph node metastasis(LNM).AIM To establish models to predict LNM in early GC(EGC),including early gastric SRCC.METHODS Clinical data from EGC patients who had undergone gastrectomy at the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2022 were reviewed.The patients were divided into three groups based on type:Pure SRCC,mixed SRCC,and non-signet ring cell carcinoma(NSRC).The risk factors were identified through statistical tests using SPSS 23.0,R,and EmpowerStats software.RESULTS A total of 1922 subjects with EGC were enrolled in this study,and included 249 SRCC patients and 1673 NSRC patients,while 278 of the patients(14.46%)presented with LNM.Multivariable analysis showed that gender,tumor size,depth of invasion,lymphovascular invasion,ulceration,and histological subtype were independent risk factors for LNM in EGC.Establishment and analysis using prediction models of EGC showed that the artificial neural network model was better than the logistic regression model in terms of sensitivity and accuracy(98.0%vs 58.1%,P=0.034;88.4%vs 86.8%,P<0.001,respectively).Among the 249 SRCC patients,LNM was more common in mixed(35.06%)rather than in pure SRCC(8.42%,P<0.001).The area under the ROC curve of the logistic regression model for LNM in SRCC was 0.760(95%CI:0.682-0.843),while the area under the operating characteristic curve of the internal validation set was 0.734(95%CI:0.643-0.826).The subgroups analysis of pure types showed that LNM was more common in patients with a tumor size>2 cm(OR=5.422,P=0.038).CONCLUSION A validated prediction model was developed to recognize the risk of LNM in EGC and early gastric SRCC,which can aid in pre-surgical decision making of the best method of treatment for patients.

Pattern of No.12a lymph node metastasis in gastric cancer

Objective:The current standard D2 lymphadenectomy for gastric cancer(GC)includes dissection of lymph nodes(LNs)along the proper hepatic artery(No.12 a),however,the survival benefit remains controversial.The purpose of this study was to evaluate the pattern of No.12 a LN metastasis(LNM)in GC and explore the indications for No.12 a LN dissection.Methods:Medical records of 413 consecutive GC patients who underwent curative surgery in Zhongshan Hospital,Fudan University between January 2015 and December 2018 were enrolled and reviewed retrospectively.The correlation between No.12 a LNM and clinicopathologic characteristics of patients was analyzed.Results:The overall incidence of No.12 a LNM was 2.67%(11/413).Tumor location(P=0.012),depth of tumor infiltration(P<0.01)and N stage(P=0.018)were significant factors associated with No.12 a LNM.All the tumors with No.12 a LNM involved the lower third of the stomach and were in T3-4 stages.Patients with No.12 a LNM had extensive LNM than those without(20.91±4.25 vs.5.0±0.54,P<0.001).For advanced GC patients(stage III/IV)with tumors involving the lower third of the stomach,the incidence of No.12 a LNM increased to 10.7%(11/103).Patients with No.12 a LNM had a significantly poorer recurrence-free survival(RFS)(P=0.005)and overall survival(OS)(P=0.017).According to the result of multivariable Cox regression,No.12 a LNM was not an independent impact factor on RFS and OS.Conclusions:The overall incidence of No.12 a LNM was low but it was much higher in GC patients who had very advanced tumors involving the lower third of the stomach.No.12 a LN dissection should be considered for these patients to improve the survival outcomes.

Seven synchronous early gastric cancer with 28 lymph nodes metastasis

An 85 year male patient complaining epigastric discomfort was admitted.From the esophagogastroduodenoscopy,three early gastric cancer(EGCa)lesions had been identified and these were diagnosed as adenocarcinoma with poorly differentiated cell type.The patient underwent operation.From the post-operative mapping,however,additional 4 EGCa lesions were found,and the patient was diagnosed with 7 synchronous EGCa.Out of the 7 EGCa lesions,6 had shown invasion only to the mucosal layer and one had shown invasion into the 1/3layer of submucosa.In spite of such superficial invasions,28 of 48 lymph nodes had been identified as metastases.The multiple lesions of EGCa do not increase the risk of lymph node metastasis,but if their differentiations are poor or if they have lympho-vascular invasion,multiple lymph node metastases could incur even if the depth of invasion is limited to the mucosal layer or the upper portion of the submucosal layer.

Risk of station 12a lymph node metastasis in patients with lowerthird gastric cancer

BACKGROUND Controversy over the issue that No.12a lymph node involvement is distant or regional metastasis remains,and the possible inclusion of 12a lymph nodes in D2 lymphadenectomy is unclear.As reported,gastric cancer(GC)located in the lower third is highly related to the metastasis of station 12a lymph nodes.AIM To investigate whether the clinicopathological factors and metastasis status of other perigastric nodes can predict station 12a lymph node metastasis and evaluate the prognostic significance of station 12a lymph node dissection in patients with lower-third GC.METHODS A total of 147 patients with lower-third GC who underwent D2 or D2+lymphadenectomy,including station 12a lymph node dissection,were included in this retrospective study from June 2003 to March 2011.Survival prognoses were compared between patients with or without station 12a lymph node metastasis.Logistic regression analyses were used to clarify the association between station 12a lymph node metastasis and clinicopathological factors or metastasis status of other perigastric nodes.The metastasis status of each regional lymph node was evaluated to identify the possible predictors of station 12a lymph node metastasis.RESULTS Metastasis to station 12a lymph nodes was observed in 18 patients with lowerthird GC,but not in 129 patients.The incidence of station 12a lymph node involvement was reported as 12.2%in patients with lower-third GC.The overall survival of patients without station 12a lymph node metastasis was significantly better than that of patients with station 12a metastasis(P<0.001),which could also be seen in patients with or without extranodal soft tissue invasion.Station 12a lymph node metastasis and extranodal soft tissue invasion were identified as independent predictors of poor prognosis in patients with lower-third GC.Advanced pN stage was defined as independent risk factor significantly correlated with station 12a lymph node positivity.Station 3 lymph node staus was also proven to be significantly correlated with station 12a lymph node involvement.CONCLUSION Metastasis of station 12a lymph nodes could be considered an independent prognosis factor for patients with lower-third GC.The dissection of station 12a lymph nodes may not be ignored in D2 or D2+lymphadenectomy due to difficulties in predicting station 12a lymph node metastasis.

Feasibility of endoscopic treatment and predictors of lymph node metastasis in early gastric cancer

BACKGROUND Endoscopic submucosal dissection (ESD) has been routinely performed in applicable early gastric cancer (EGC) patients as an alternative to conventional surgical operations that involve lymph node dissection. The indications for ESD have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. The risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for EGC. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. In addition, whether patients who meet the expanded indications for ESD can be managed safely remains controversial. AIM To determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC. METHODS We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients’ clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses. RESULTS LNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren’s types. Multivariate analysis demonstrated SM1 invasion (odds ration [OR]= 2.285, P = 0.03), SM2 invasion (OR = 3.230, P < 0.001), LVI (OR = 15.702, P < 0.001), mucinous adenocarcinoma (OR = 2.823, P = 0.015), and large lesion size (OR = 1.900, P = 0.006) to be independent risk factors. CONCLUSION The absolute indications for ESD are reasonable, and the feasibility of expanding the indications for ESD requires further investigation. The predictors of LNM include invasion depth, LVI, mucinous adenocarcinoma, and lesion size.

Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

Accurate prediction of lymph node(LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer(EGC). However,consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search,we identified several independent variables associated with LN metastasis in EGC,which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand,even if we use these promising parameters,we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN(SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review,we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition,we evaluated the history of sentinel node navigation surgery and the usefulness for EGC.

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics.METHODS We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy.PD-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive score.All PD-L1+PT staged as pN+were also tested for PD-L1 expression in their LNM.PD-L1(-)GC with pN+served as the comparison group.RESULTS Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the LNM.Regarding PD-L1(-)PT,9.1%(4/44)had PD-L1+in the LNM.The agreement between PT and LNM had a kappa value of 0.483.Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites.There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM.This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Risk factors for lymph node metastasis and evaluation of reasonable surgery for early gastric cancer

AIM: To give the evidence for rationalizing surgical therapy for early gastric cancer with different lymph node status. METHODS: A series of 322 early gastric cancer patients who underwent gastrectomy with more than 15 lymph nodes retrieved were reviewed in this study. The rate of lymph node metastasis was calculated. Univariate and multivariate analyses were performed to evaluate the independent factors for predicting lymph node metastasis. RESULTS: No metastasis was detected in No.5, 6 lymph nodes (LN) during proximal gastric cancer total gastrectomy, and in No.10, 11p, 11d during for combined resection of spleen and splenic artery and in No.15 LN during combined resection of transverse colon mesentery. No.11p, 12a, 14v LN were proved negative for metastasis. The global metastastic rate was 14.6% for LN, 5.9% for mucosa, and 22.4% for submucosa carcinoma, respectively. The metastasis in group Ⅱ?was almost limited in No.7, 8a LN. Multivariate analysis identified that the depth of invasion, histological type and lymphatic invasion were independent risk factors for LN metastasis. No metastasis from distal cancer (≤ 1.0 cm in diameter) was detected in group Ⅱ?LN. The metastasis rate increased significantly when the diameter exceeded 3.0 cm. All tumors (≤ 1.0 cm in diameter) with LN metastasis and mucosa invasion showed a depressed macroscopic type, and all protruded carcinomas were > 3.0 cm in diameter. CONCLUSION: Segmental/subtotal gastrectomy plus D1/D1 + No.7 should be performed for carcinoma (≤ 1.0 cm in diameter, protruded type and mucosa invasion).Subtotal gastrectomy plus D2 or D1 + No.7, 8a, 9 is the most rational operation, whereas No.11p, 12a, 14v lymphadenectomy should not be recommended routinely for poorly differentiated and depressed type of submucosa carcinoma (> 3.0 cm in diameter). Total gastrectomy should not be performed in proximal, so does combined resection or D2+/D3 lymphadenectomy.

STAT-3 correlates with lymph node metastasis and cell survival in gastric cancer

AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor of cytokine signaling-1(SOCS-1),survivin and Bcl-2 in gastric cancer patients after gastrectomy by immunohistochemical method.In addition,in situ hybridization was used to further demonstrate the mRNA expression of STAT3 in gastric cancer.RESULTS:With the univariate analysis,expressions of STAT3,pSTAT3,SOCS-1,survivin and Bcl-2,the size of primary tumor and the lymph node metastasis were found to be associated with the overall survival(OS) of gastric cancer patients.However,only pSTAT3 expression and the lymph node metastasis were identified as the independent factors of OS of gastric cancer with multivariate analysis.STAT3 expression was correlated with the lymph node metastasis.There were positive correlations between expressions of STAT3,survivin,Bcl-2 and pSTAT3 in gastric cancer,whereas there was negative correlation between STAT3 expression and SOCS-1 expression in gastric cancer.CONCLUSION:STAT3 can transform into pSTAT3 to promote the survival and inhibit the apoptosis of gastric cancer cells.SOCS-1 might be the valid molecular antagonist to inhibit the STAT3 expression in gastric cancer.

Risk of lymph node metastasis in mixed-type early gastric cancer determined by the extent of the poorly differentiated component

AIM: To predict the rate of lymph node(LN) metastasis in diffuse- and mixed-type early gastric cancers(EGC) for guidelines of the treatment.METHODS: We reviewed 550 cases of EGC withdiffuse- and mixed-type histology. We investigated the clinicopathological factors and histopathological components that influence the probability of LN metastasis, including sex, age, site, gross type, presence of ulceration, tumour size, depth of invasion, perineural invasion, lymphovascular invasion, and LN metastasis status. We reviewed all slides and estimated the proportions of each tumour component; pure diffuse type, mixed-predominantly diffuse type(diffuse > intestinal type), mixed-predominantly intestinal type(intestinal > diffuse type), and mixed diffuse = intestinal type. We calculated the extents of the respective components.RESULTS: LN metastasis was observed in 12.9%(71/550) of early gastric cancers cases [15/288 mucosal EGCs(5.2%) and 56/262 submucosal EGCs(21.4%)]. Of 550 cases, 302 were diffuse-type and 248 were mixed-type EGCs. Of 248 mixed-type EGCs, 163 were mixed-predominantly diffuse type, 82 were mixed-predominantly intestinal type, and 3 were mixed diffuse = intestinal type. Mixed-type cases with predominantly diffuse type histology showed a higher frequency of LN metastasis(20.2%) than cases of pure diffuse type(9.3%) and predominantly intestinal type(12.2%) histology. We measured the dimensions of each component(intestinal and diffuse type) to determine the association of the extent of each component with LN metastasis in mixed-type gastric carcinoma. The total tumour size and the extent of poorly differentiated components was associated with LN metastasis, while that of signet ring cell components was not.CONCLUSION: We recommend careful identification and quantitative evaluation of mixed-type early gastric cancer components after endoscopic resection to determine the intensity of the treatment.

Construction and external validation of a nomogram that predicts lymph node metastasis in early gastric cancer patients using preoperative parameters

Objective: To create a nomogram to predict the incidence of lymph node metastasis(LNM) in early gastric cancer(EGC) patients and to externally validate the nomogram.Methods: To construct the nomogram,we retrospectively analyzed a primary cohort of 272 EGC patients.Univariate analysis and a binary logistic regression were performed.A nomogram predicting the incidence of LNM in EGC patients was created.The discrimination ability of the nomogram was measured using the concordance index(c-index),and the nomogram was also calibrated.Then,another prospective cohort of 81 patients was analyzed to validate the nomogram.Results: In the primary cohort,LNM was pathologically confirmed in 37(13.6%) patients.In multivariate analysis,the presence of an ulcer,the maximum lesion diameter observed via gastroscopy,the thickness of the lesion observed via endoscopic ultrasonography,and the presence of enlarged lymph nodes on computed tomography(CT) were independent risk factors for LNM.A nomogram was then created based on the regression model with the c-index of 0.905,and the calibration curve of the nomogram fell approximately on the ideal 45-degree line.The cut-off score of the nomogram was 110,and the sensitivity,specificity,positive predictive and negative predictive values of the nomogram in the primary cohort were 81.1%,86.0%,47.6% and 96.7%,respectively,and in the prospective validation cohort were 75.0%,91.0%,60.0% and 95.5%,respectively.The calibration curve of the external validation cohort was almost on the 45-degree line.Conclusions: We developed an effective nomogram predicting the incidence of LNM for EGC patients.

Association of serum vascular endothelial growth factor-C and lymphatic vessel density with lymph node metastasis and prognosis of patients with gastric cancer

AIM： To investigate whether serum vascular endothelial growth factor-C （SVEGF-C）, VEGF-C, and lymphatic vessel density （LVD） in tumor tissues are related to lymph node metastasis （LNM） and prognosis in gastric cancer. METHODS： SVEGF-C levels of 80 gastric cancer patients and 20 healthy donors were examined using ELISA. VEGF-C expression and LVD were examined using immunohistochemical staining. Kaplan-Meier survival analysis was performed to determine their influence on the prognosis of the patients. RESULTS： The SVEGF-C level in gastric cancer patients （595.9 ± 201.0 ng/L） was significantly higher （P = 0.000） than controls （360.0 ± 97.4 ng/L）. Both SVEGF-C and LVD were significantly higher in poorly differentiated adenocarcinomas, T3 and T4, LNM, distant metastasis, and pTNM groups Ⅲ and Ⅳ （P = 0.000）. The sensitivity and specificity of SVEGF-C for predicting LNM were 82.8% and 81.8%, respectively （cut-off = 542.5 ng/L）. The positive expression rate of VEGF-C was significantly higher in cancerous than in normal tissues （65% vs 20%; P = 0.001）. VEGF-C expression up-regulation was significantly related to differentiation, depth of invasion, LNM, distant metastasis, and pTNM stage （P = 0.000）. LVD was 10.7 ± 3.1/200 HP in the experimental group vs 4.9 ± 1.3/200 HP in controls （P = 0.000）; LVD in cancerous tissues with and without LNM was 12.0 ± 2.7/200 HP vs 7.6 ± 0.5/200 HP, respectively （P = 0.000）. SVEGF-C and LVD were significantly higher in VEGF-C positive than in negative patients （P = 0.000）; SVEGF-C level was related to LVD （P = 0.000）. Kaplan-Meier survival analysis factors predicating poor prognosis were： SVEGF-C level （P = 0.001）, VEGF-C expression and LVD （both P = 0.000）. CONCLUSION： SVEGF-C level, VEGF-C and LVD are related to LNI and poor prognosis of patients with gastric cancer, SVEGF-C may be a biomarker for LNI in gastric cancer,

Prognostic role of lymph node metastasis in early gastric cancer

Objective： To clarify the relationship between clinicopathological features and lymph node metastasis and to propose the potential indications of lymph node metastasis for prognosis in early gaswic cancer （EGC） patients. Methods： We retrospectively observed 226 EGC patients with lymph node resection, and analyzed the associations between lymph node metastasis and clinicopathological parameters using the chi-square test in univariate analysis and logistic regression analysis in multivariate analysis. Overall survival analysis was determined using the Kaplan-Meier and log-rank test. We conducted multivariate prognosis analysis using the Cox proportional hazards model. Results： Of all the EGC patients, 7.5% （17/226） were histologically shown to have lymph node metastasis. The differentiation, lymphovascular invasion and depth of invasion were independent risk factors for lymph node metastasis in EGC. The 5- and 10-year survival rates were significantly lower in patients with lymph node metastasis than in those without and the patients also had shorter progress-free survival time. Lymph node metastasis and tumor size were independent prognostic factors for EGC. The status of the lymph nodes was a significant factor in predicting recurrence or metastasis after surgery. Conclusions： The undifferentiated carcinoma and lymphovascular and/or submucosal invasion were associated with a higher incidence of lymph node metastasis in EGC patients, whom need to perform subsequent D2 lymphadenectomy or laparoscopic lymph node dissection and more rigorous follow-up or additional chemotherapy/radiation after D2 gastrectomy for poor prognosis and high recurrence/metastasis rate.

Potentially predictive microRNAs of gastric cancer with metastasis to lymph node

AIM:To detect the expression of 60 microRNAs(miRNAs)in gastric cancer tissues and find new predictive biomarkers of gastric cancer with metastasis.METHODS:The expressions of 60 candidate miRNAs in 30 gastric cancer tissues and paired normal tissues were detected by stem-loop real-time reverse transcription-polymerase chain reaction.After primary screening of miRNAs expression,5 selected miRNAs were further testified in another 22 paired gastric tissues.Based on the expression level of miRNAs and the status of metastasis to lymph node(LN),receiver-operating-characteristic(ROC)curve were used to evaluate their ability in predicting the status of metastasis to LN.RESULTS:Thirty-eight miRNAs expressions in gastric cancer tissues were significantly different from those in paired normal tissues(P<0.01).Among them,31miRNAs were found to be up-expressed in cancer tissues and 1 miRNAs were down-expressed≥1.5 fold vs paired normal gastric tissue.Five microRNAs(miR-125a-3p,miR-133b,miR-143,miR-195 and miR-212)were differently expressed between different metastatic groups in 30 gastric cancer biopsies(P<0.05).Partial correlation analysis showed that hsa-mir-212 and hsa-mir-195 were correlated with the status of metastasis to LN in spite of age,gender,tumor location,tumor size,depth of invasion and cell differentiation.ROC analysis indicated that miR-212 and miR-195 have better sensi-tivities(84.6%and 69.2%,respectively)and specifici-ties(both 100%)in distinguishing biopsies with metastasis to LN from biopsies without metastasis to LN.CONCLUSION:miR-212 and miR-195 could be independent biomarkers in predicting the gastric cancer with metastasis to LN.

CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric carcinoma

AIM To investigate the role of CXC chemokine receptor (CXCR)-7 and CXCL12 in lymph node and liver metastasis of gastric carcinoma. METHODS In 160 cases of gastric cancer, the expression of CXCR7 and CXCL12 in tumor and matched tumoradjacent non-cancer tissues, in the lymph nodes around the stomach and in the liver was detected using immunohistochemistry to analyze the relationship between CXCR7/CXCL12 expression and clinicopathological features and to determine whether CXCR7 and CXCL12 constitute a biological axis to promote lymph node and liver metastasis of gastric cancer. Furthermore, the CXCR7 gene was silenced and overexpressed in human gastric cancer SGC-7901 cells, and cell proliferation, migration and invasiveness were measured by the MTT, wound healing and Transwell assays, respectively. RESULTS CXCR7 expression was up-regulated in gastric cancer tissues (P = 0.011). CXCR7/CXCL12 expression was significantly related to high tumor stage and lymph node (r = 0.338, P = 0.000) and liver metastasis (r = 0.629, P = 0.000). The expression of CXCL12 in lymph node and liver metastasis was higher than that in primary gastric cancer tissues (chi(2) = 6.669, P = 0.010; chi(2) = 25379, P = 0.000), and the expression of CXCL12 in lymph node and liver metastasis of gastric cancer was consistent with the positive expression of CXCR7 in primary gastric cancer (r = 0.338, P = 0.000; r = 0.629, P = 0.000). Overexpression of the CXCR7 gene promoted cell proliferation, migration and invasion. Silencing of the CXCR7 gene suppressed SGC-7901 cell proliferation, migration and invasion. Human gastric cancer cell lines expressed CXCR7 and showed vigorous proliferation and migratory responses to CXCL12. CONCLUSION The CXCR7/CXCL12 axis is involved in lymph node and liver metastasis of gastric cancer. CXCR7 is considered a potential therapeutic target for the treatment of gastric cancer.

Unveiling lymph node metastasis in early gastric cancer

With respect to gastric cancer treatment,improvements in endoscopic techniques and novel therapeutic modalities[such as endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)]have been developed.Currently,EMR/ESD procedures are widely accepted treatment modalities for early gastric cancer(EGC).These procedures are most widely accepted in Asia,including in Korea and Japan.In the present era of endoscopic resection,accurate prediction of lymph node(LN)metastasis is a critical component of selecting suitable patients for EMR/ESD.Generally,indications for EMR/ESD are based on large Japanese datasets,which indicate that there is almost no risk of LN metastasis in the subgroup of EGC cases.However,there is some controversy among investigators regarding the validity of these criteria.Further,there are currently no accurate methods to predict LN metastasis in gastric cancer(for example,radiologic methods or methods based on molecular biomarkers).We recommend the use of a 2-step method for the management of early gastric cancer using endoscopic resection.The first step is the selection of suitable patients for endoscopic resection,based on endoscopic and histopathologic findings.After endoscopic resection,additional surgical intervention could be determined on the basis of a comprehensive review of the endoscopic mucosal resection/endoscopic submucosal dissection specimen,including lymphovascular tumor emboli,tumor size,histologic type,and depth of invasion.However,evaluation of clinical application data is essential for validating this recommendation.Moreover,gastroenterologists,surgeons,and pathologists should closely collaborate and communicate during these decisionmaking processes.

Survival prognostic analysis of laparoscopic D2 radical resection for locally advanced gastric cancer: A multicenter cohort study

BACKGROUND With the development of minimally invasive surgical techniques,the use of laparoscopic D2 radical surgery for the treatment of locally advanced gastric cancer(GC)has gradually increased.However,the effect of this procedure on survival and prognosis remains controversial.This study evaluated the survival and prognosis of patients receiving laparoscopic D2 radical resection for the treatment of locally advanced GC to provide more reliable clinical evidence,guide clinical decision-making,optimize treatment strategies,and improve the survival rate and quality of life of patients.METHODS A retrospective cohort study was performed.Clinicopathological data from 652 patients with locally advanced GC in our hospitals from December 2013 to December 2023 were collected.There were 442 males and 210 females.The mean age was 57±12 years.All patients underwent a laparoscopic D2 radical operation for distal GC.The patients were followed up in the outpatient department and by telephone to determine their tumor recurrence,metastasis,and survival.The follow-up period ended in December 2023.Normally distributed data are expressed as the mean±SD,and normally distributed data are expressed as M(Q1,Q3)or M(range).Statistical data are expressed as absolute numbers or percentages;theχ^(2) test was used for comparisons between groups,and the Mann-Whitney U nonparametric test was used for comparisons of rank data.The life table method was used to calculate the survival rate,the Kaplan-Meier method was used to construct survival curves,the log rank test was used for survival analysis,and the Cox risk regression model was used for univariate and multifactor analysis.RESULTS The median overall survival(OS)time for the 652 patients was 81 months,with a 10-year OS rate of 46.1%.Patients with TNM stages II and III had 10-year OS rates of 59.6%and 37.5%,respectively,which were significantly different(P<0.05).Univariate analysis indicated that factors such as age,maximum tumor diameter,tumor diffe-rentiation grade(low to undifferentiated),pathological TNM stage,pathological T stage,pathological N stage(N2,N3),and postoperative chemotherapy significantly influenced the 10-year OS rate for patients with locally advanced GC following laparoscopic D2 radical resection for distal stomach cancer[hazard ratio(HR):1.45,1.64,1.45,1.64,1.37,2.05,1.30,1.68,3.08,and 0.56 with confidence intervals(CIs)of 1.15-1.84,1.32-2.03,1.05-1.77,1.62-2.59,1.05-1.61,1.17-2.42,2.15-4.41,and 0.44-0.70,respectively;P<0.05].Multifactor analysis revealed that a tumor diameter greater than 4 cm,low tumor differentiation,and pathological TNM stage III were independent risk factors for the 10-year OS rate in these patients(HR:1.48,1.44,1.81 with a 95%CI:1.19-1.84).Additionally,postoperative chemotherapy emerged as an independent protective factor for the 10-year OS rate(HR:0.57,95%CI:0.45-0.73;P<0.05).CONCLUSION A maximum tumor diameter exceeding 4 cm,low tumor differentiation,and pathological TNM stage III were identified as independent risk factors for the 10-year OS rate in patients with locally advanced GC following laparoscopic D2 radical resection for distal GC.Conversely,postoperative chemotherapy was found to be an independent protective factor for the 10-year OS rate in these patients.