Staging Of Gastric Cancer Research Articles

Prognostic Value of PD-L1 Immunohistochemical Marker in Gastric Carcinoma and Its Correlation with HER2 Status.

Objective:Programmed death-ligand 1 (PD-L1) and human epidermal growth factor receptor 2 (HER2) are currently considered as prognostic markers and therapeutic targets in many human cancers. This study aims to evaluate immunohistochemical (IHC) expression of PD-L1 in gastric cancer (GC) and explore its prognostic role in terms of association with HER2 expression, different clinico-pathological variables, in particular density and cluster designation (CD)8 positivity in tumor infiltrating lymphocytes (TILs) and with patients’ disease-free and overall survival (DFS, OS). Methods:This retrospective cohort study included 111 diagnosed primary GC patients who underwent surgical resection at the Gastrointestinal Surgery Center (GISC), Faculty of Medicine, Mansoura University, Egypt. After demographic, clinicopathological and survival data collection, histopathological evaluation was done for GC typing, staging and assessment of the histopathological prognostic parameters. IHC was performed for PD-L1, HER2 and CD8. PDL-1 was scored using the Combined Positive Score (CPS). Results: PD-L1 was expressed in 43.2% of GCs at a CPS cut-off value ≥ 1. PDL-1 positivity was significantly associated with high TILs and CD8+ TILs (p=0.008, 0.016 respectively), indicating its contribution to tumor microenvironment along with the TILs. Multivariate analysis spotted PD-L1 positivity as an independent prognostic predictor for shorter OS in GC (p=0.013), with a tendency toward shorter DFS. Only 9.9% GCs were HER2 positive (score +3) with no significant association with PD-L1. Conclusion:PDL-1 is a promising prognostic and therapeutic target in GC that may direct the selection of patients for immunotherapy and checkpoint-blockade (pembrolizumab) therapy.

The clinical features, management, and survival of elderly patients with gastric cancer.

It is anticipated that the number of elderly patients with gastric cancer (GC) will increase with population aging; however, most studies on GC set the upper age limit at 80 years old, studies on the prognosis of elderly patients with GC over 80 years old is very limited. In this study, we conducted a retrospective analysis of this sub-cohort. This retrospective cohort study aimed to analyze the clinical data of patients aged >80 who died of GC in People's Liberation Army General Hospital between 1985 and 2020. We collected clinical informations about pathological GC types, differentiation degrees, clinical stages, anatomic sites and Bormann types of the selected case. Characteristics of participants, such as smoking, drinking, and tumor history, age, gender, and complications, were also recorded. The Kaplan-Meier method, a multivariate Cox multivariate proportional hazard model, and logistic regression were used to analyze the patient overall survival (OS) rates and treatment outcomes. The study included 92 patients (83.7% men) with a median OS of 45 months. The most common site for GC was the gastric antrum (GA), the most common site of metastatic spread was the liver, and the most common pathological GC type was tubular adenocarcinoma/papillary adenocarcinoma (TAC/PAC). Furthermore, the prevalent complications were hypertension, coronary heart disease, and diabetes. Diabetes was a risk factor affecting the total survival time [hazard ratio (HR) =2.326, P=0.029]. The most often-used GC treatment was curative surgery. The survival time was significantly longer in the curative surgery group and curative surgery + adjuvant chemotherapy group compared with the support care group (HR =0.119, P=0.001; HR =0.110, P=0.001). There was no significant difference in survival time among the palliative chemotherapy group, palliative surgery group, and support care group. Tumor staging was significantly correlated with OS rate, the median survival time of patients at stage III and stage IV GC were significantly lower than the median survival time of patients at stage I GC (HR =6.235, P=0.001; HR =30.955, P=0.001). For patients over 80 years old with good physical conditions in the early stage of GC, more active treatment can still bring better prognosis.

MiR-4484 regulates the expression of integrin α 6 in gastric cancer tissues and its significance

Objective: To investigate the relationship between the expression of integrin α 6 (ITGA6), miR-4484 and the pathologic stage of gastric cancer. Methods: Gastric cancer tissues and normal gastric mucosa tissues adjacent to cancer (>5 cm from tumor margin) of 30 patients with primary gastric cancer who underwent direct surgical resection without adjuvant therapy from June to September 2017 in West China Hospital of Sichuan University were selected. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of miR-4484 and ITGA6, western blot was used to detect the expression level of ITGA6 protein, dual luciferase reporter gene was used to verify the relationship between ITGA6 and miR-4484. Spearman's correlation analysis was used to determine the relationship between miR-4484 and ITGA6 expression levels in gastric cancer tissues. Results: The expression level of ITGΑ6 in gastric cancer (32.30±13.47) was higher than that in matched normal gastric tissues (24.55±10.25, P=0.015), the area under the receiver operating characteristic (ROC) curve was 0.660 and the diagnostic sensitivity and specificity were 43.3% and 96.7%, respectively. The expression level of miR-4484 in gastric cancer (4.11±2.87) was lower than that of matched normal gastric tissues (5.75±2.80, P=0.029), the area under the ROC curve was 0.690 and the diagnostic sensitivity and specificity were 30.0% and 86.7%, respectively. The expression level of miR-4484 was negatively correlated with ITGA6 in gastric cancer tissues (r=-0.621, P<0.001). The expression level of ITGA6 protein in gastric cancer tissues (0.65±0.19) was higher than that in normal adjacent tissues (0.26±0.12, P<0.001). Compared with ITGA6 3'UTR wild-type+ miR-NC group, ITGA6 3'UTR wild-type+ miRNA mimics group had lower luciferase activity (50.69±5.10, 34.00±1.19, P<0.001), while the luciferase activity of ITGA6 3'UTR wild-type+ ASO miR-4484 group was higher than that of ITGA6 3'UTR wild-type+ miR-NC group (82.44±6.37, 50.69±5.10, P<0.001), indicated that ITGA6 was the direct target gene of miR-4484. The expression levels of miR-4484 in T1, T2, T3 and T4 (4a and 4b) gastric cancer tissues were 9.98±2.24, 5.28±2.03, 2.92±2.04 and 4.11±2.87, respectively, with statistical significance (P<0.001). The expression levels of ITGA6 in N0, N1, N2 and N3 gastric cancer tissues were 29.55±8.32, 21.71±3.75, 24.60±8.79 and 40.69±15.83, respectively, with statistical significance (P=0.022). The expression levels of miR-4484 in N0, N1, N2 and N3 gastric cancer tissues were 5.01±3.52, 5.48±2.76, 5.88±1.83 and 2.30±1.56, respectively, with statistical significance (P=0.032). The expression levels of ITGA6 in M0 and M1 gastric cancer tissues were 26.28±7.66 and 52.08±8.12, respectively, with statistical significance (P<0.001). The expression levels of miR-4484 in M0 and M1 gastric cancer tissues were 4.95±2.74 and 1.34±0.80, respectively, with statistical significance (P<0.001). Conclusions: ITGA6 is upregulated in gastric cancer tissues, while miR-4484 is downregulated in the gastric cancer group, and its expression level is related to the clinicopathological features of gastric cancer. ITGA6 is the direct target gene of miR-4484, implicates that miR-4484 may inhibit the invasion and metastasis of gastric cancer by regulating the expression of ITGA6. Both miR-4484 and ITGA6 may be the new prognostic markers and potential therapeutic targets of gastric cancer.

Yield of routine staging laparoscopy in patients with gastric cancer in Alberta, Canada.

Background:Despite guidelines recommending diagnostic laparoscopy in patients with gastric cancer, implementation is low. We aimed to explore trends in the use of laparoscopy for staging of gastric cancer in Alberta, Canada, determine the rate of positive findings and identify factors predictive of positive staging laparoscopy (SL) findings in this patient population.Methods:In August 2018, we sent a survey to all general surgeons in Alberta who were members of the Alberta Association of General Surgeons to identify those treating gastric cancer. The survey inquired about type of practice (academic or community), gastric cancer case volume, routine versus selective use of SL and, if selective use of SL, criteria used to select cases. Participants were also asked to provide data from their SL cases from July 2007 to February 2019. We double-checked surgeon records with chart review. The primary outcome was evidence of metastatic disease on SL or cytologic examination or both. We performed logistic regression analysis to identify factors predictive of positive laparoscopy findings.Results:The survey was completed by 41 of 127 surgeons (response rate 32.3%). We reviewed 116 cases from 5 surgeons at 4 centres. Gross metastatic disease or positive findings on cytologic examination or both were identified in 37 patients (31.9%). On univariate analysis, the following were associated with an increased risk of identification of metastatic disease at laparoscopy: visualization of the primary tumour on computed tomography (CT) (odds ratio [OR] 9.8, 95% confidence interval [CI] 1.2–76.5), presence of abdominal lymphadenopathy greater than 1 cm (OR 2.4, 95% CI 1.1–5.4) and presence of ascites (OR 19.1, 95% CI 2.2–161.8). Visualization of the primary tumour on CT (OR 8.4, 95% CI 1.0–68.3) and the presence of ascites (OR 15.9, 95% CI 1.8–137.0) remained statistically significant predictors on multivariate analysis.Conclusion:Metastatic disease was identified at SL in almost one-third of cases, which suggests that SL should still be used routinely in gastric cancer staging in Canadian centres. Our study identified several preoperative imaging findings associated with evidence of metastatic disease on laparoscopy; however, further studies are needed to establish robust predictors of positive findings before advocating for a selective SL approach.

Kinesin family member 2A links with advanced tumor stage, reduced chemosensitivity and worse prognosis in gastric cancer.

BackgroundKinesin family member 2A (KIF2A) induces gastric cancer (GC) growth and invasion, while its clinical relevance in GC patients is not reported. This study aimed to investigate the linkage of KIF2A with clinicopathological features, prognosis, and chemosensitivity of GC.MethodsA total of 160 surgical GC patients were reviewed, with their tumor and adjacent tissues acquired for immunohistochemical (IHC) assay to measure KIF2A expression, then scored by a semi‐quantitative method (IHC score: 0–12). KIF2A siRNA or nonsense‐siRNA were transfected into HGC‐27 and NCI‐N87 cells underwent various concentrations of capecitabine or oxaliplatin treatment followed by chemosensitivity assessment.ResultsKinesin family member 2A expression was elevated in the tumor tissue compared to the adjacent tissue (IHC score: 5.6 ± 3.1 vs. 2.9 ± 1.7, p < 0.001). Besides, tumor KIF2A expression was related to larger tumor size (p = 0.014), higher N stage (p = 0.004) and TNM stage (p = 0.011); however, it was not linked with other clinicopathological features (all p > 0.05). Signally, tumor KIF2A high expression predicted poor overall survival (p = 0.037). After adjustment via multivariate Cox's regression, tumor KIF2A high expression independently linked with worse disease‐free survival (p = 0.033). Finally, KIF2A knockdown improved the oxaliplatin chemosensitivity vastly but only slightly affected capecitabine chemosensitivity in HGC‐27 and NCI‐N87 cells.ConclusionKinesin family member 2A reflects larger tumor size, advanced TNM stage, improved chemosensitivity, and predicts unfavorable survival in GC.

Relationship between nutritional biomarkers and occlusal status in gastric cancer patients using the Eichner index: Observational study.

Systemic inflammatory responses and nutritional status are useful prognostic factors in gastric cancer patients. Since oral hypofunction causes undernutrition, we cross-sectionally investigated whether nutritional biomarkers were affected by the occlusal supporting zone status.In 114 gastric cancer patients, the gastric cancer stage, body mass index, albumin levels, total lymphocyte counts, cholesterol levels, C-reactive protein levels, and 4 nutritional biomarkers - the Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio, prognostic nutrition index (PNI), and controlling nutritional status (CONUT) - were evaluated. Oral conditions were assessed by determining the number of remaining teeth. The occlusal supporting status was based on the Eichner classification. Patients were assigned into 3 groups per their occlusal status, and mean values were compared using the Kruskal-Wallis test. The mean age and body mass index were 72.2 ± 8.5 (50-89) years and 22.0 ± 3.6 (14.8-33.4), respectively. There were 42, 39, 23, and 10 patients in stages I, II, III, and IV, respectively. The mean number of remaining teeth was 18.1 ± 9.5. According to the Eichner classification, there were 45, 42, and 27 patients in groups A, B, and C, respectively. The GPS and neutrophil-lymphocyte ratio values and CONUT frequencies between groups A and C were significantly different (P = .033, P = .00097, P = .04, respectively; Mann-Whitney U test). PNI values were lower in group C with poor occlusal support zones than in group A with stable occlusal support zones.Occlusal supporting zone reductions were undernutrition associated. Eichner Class C patients with few occlusal supporting zones had poor GPS, PNI, and CONUT values and were undernourished.

Accuracy of preoperative staging of gastric stump cancer.

In this study, the accuracy of preoperative staging for gastric stump cancer, which has not been thoroughly investigated since the condition is rare, was investigated using computed tomography and gastroscopic imaging. Between February 1994 and April 2018, 49 patients with gastric stump cancer, following subtotal or total gastrectomy, were reviewed retrospectively. Preoperative diagnoses of clinical T and clinical N categories were compared with post-operative pathological diagnoses (pT and pN categories). Positive predictive values, accuracy, sensitivity and specificity were also evaluated. The overall accuracy of T staging was 40.8%. The positive predictive value for cT3/T4 was 96.3%, whereas the positive predictive value for cT1/T2 was 72.7%. The overall accuracy for N staging was 61.2%. The positive predictive value of lymph node positive patients was 73.3%. The positive predictive value and sensitivity of over stage II were 96.6% and 84.8%, respectively. The accuracy of preoperative diagnosis using both computed tomography and gastroscopy imaging may be feasible for T3/T4 advanced gastric stump cancer, whereas diagnosing T1/2 gastric stump cancer must be carefully considered due to high misdiagnosis rates, relating to depth.

Kidney Transplant Recipients Have Higher Malignancy Prevalence Than Hemodialyzed Patients

Kidney transplant is the preferred therapy for end-stage kidney disease; however, it has been associated with some serious complications, including malignancy, which became the second leading cause of death among kidney allograft recipients. The aim of this study was to assess the prevalence of malignancy in hemodialyzed patients and in kidney transplant recipients. A cross-sectional study was conducted in 114 prevalent hemodialyzed patients, including 7 on the waiting list and 350 kidney allograft recipients. Hemodialyzed patients and kidney allograft recipients did not differ in regard to sex, dialysis vintage, and cause of end-stage renal failure, but were significantly older. Among wait-listed patients, only 1 had a history of malignancy (gastric cancer stage G1). Among kidney allograft recipients, in 70 patients, malignancy developed (in total 20% of the studied population). The leading malignancy was skin cancer (18 cases), followed by post-transplant lymphoproliferative disorder (PTLD) in 10 cases, lung cancer (small cell and non-small cell lung cancer; 4 cases), renal cell carcinoma (3 cases), brain cancer (glioma; 3 cases), colorectal cancer (3 cases), Kaposi sarcoma (2 cases), Merkel carcinoma (2 cases), metastatic disease of unknown origin (2 cases), and other 23 malignancies were in a single patient (including 1 leukemia and 1 multiple myeloma). Twenty-six deaths were recorded in kidney allograft recipients with malignancy, mainly in PTLD, Kaposi sarcoma, Merkel carcinoma, sarcoma, glioma, and melanoma. Despite the lower prevalence of malignancy on hemodialyzed population, cancer screening in both potential transplant recipients and kidney allograft recipients is a prerequisite, because nowadays there is a scarcity of data in this area. It may be due to previous immunosuppression, long-term dialysis vintage, immunocompromised status, and immunosuppressive therapy after transplant, in particular in high-risk patients.

Thrombospondin-2 holds prognostic value and is associated with metastasis and the mismatch repair process in gastric cancer

BackgroundThis study aims to investigate thrombospondin 2 (TSP2) expression levels in gastric cancer (GC) and determine the relationship between TSP2 and clinical characteristics and prognosis.MethodsThe online database Gene Expression Profile Interactive Analysis (GEPIA) was used to analyse TSP2 mRNA expression levels in GC. The Kaplan–Meier plotter prognostic analysis tool was used to evaluate the influence of TSP2 expression on clinical prognosis in GC patients. TSP2 expression levels were analysed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. The relationship between the clinicopathological characteristics and prognosis of GC patients was assessed. Transwell experiments were used to evaluate the effect of TSP2 on HGC27 and AGS cell invasion and migration. The EdU experiment was used to detect the effect of transfection of TSP2 on cell proliferation, and the flow cytometry experiment was used to detect the effect of TSP2 on cell apoptosis and the cell growth cycle. Western blotting (Wb) technology was used to detect MMP, E-cadherin, N-cadherin, Vimentin, Snail, AKT, PI3K, and VEGF protein expression in HGC27 cells.ResultsCompared with normal tissues, TSP2 mRNA expression in GC was significantly upregulated and was closely related to the clinical stage of GC. High TSP2 expression significantly affected the OS, FP and PPS of patients with GC. Among these patients, TSP2 expression levels did not affect the prognosis of patients with GC in the N0 subgroup but significantly affected the prognosis of patients with GC in the N (1 + 2 + 3) subgroup. TSP2 protein expression levels were significantly higher in GC tissue compared with normal tissues (P < 0.01). The overall survival (OS) and relapse-free survival (RFS) of patients with high TSP2 expression were lower than those of patients with low TSP2 expression. Cells transfected with the TSP2-silencing sequence exhibited increased apoptosis and inhibition of proliferation, migration and invasion. AKT and PI3K expression in cells was significantly downregulated (P < 0.01). AKT, PI3K and VEGF expression in cells transfected with the TSP2 silencing sequence was significantly reduced. Proliferation, migration, invasion ability, and TSP2 expression levels significantly correlated with mismatch repair genes, such as PMS2, MSH6, MSH2, and MLH1 (P < 0.05).ConclusionTSP2 expression is significantly increased in GC. TSP2 expression is closely related to metastasis and the mismatch repair process in GC patients and affects GC patient prognosis. The mechanism may involve regulating gastric cancer cell proliferation and migration by modulating the VEGF/PI3K/AKT signalling pathway. TSP2 is a potential marker and therapeutic target for the prognosis of GC patients.

N6-Methyladenosine Regulators Promote Malignant Progression of Gastric Adenocarcinoma.

N6-methyladenosine (m6A) RNA methylation is dynamically and reversibly regulated by methyltransferases, binding proteins, and demethylases. The restoration of m6A to adenosine could result in demethylation modifications. Abnormalities in m6A epigenetic modifications in cancer are of increasing interest in recent years. According to the progression and prognostic performance of m6A epigenetic modifications in gastric adenocarcinoma (STAD), this study comprehensively analyzed the m6A modification patterns of gastric adenocarcinoma specimens in The Cancer Genome Atlas (TCGA) database based on 20 m6A regulators. Here, we found that 20 m6A RNA methylation regulators were high-expressed in gastric adenocarcinoma. m6A RNA methylation regulators were closely associated with pT staging of gastric cancer. Based on such findings, we developed a prognostic model using four m6A RNA methylation regulators (IGF2BP1, RBM15, FTO, ALKBH5), and the FTO was confirmed as an independent prognostic marker.

RETRACTED: PINK1 deficiency in gastric cancer compromises mitophagy, promotes the Warburg effect, and facilitates M2 polarization of macrophages.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and authors. Following the publication of the above article, the Editor was notified by a concerned reader that the authors supplied duplicated images. Specifically, that in Fig. 5A, both FACS panels are identical and in Fig. 5E, two different proteins (HK2 and PDK1) have the same western blot. After checking the data in relation with Fig. 5A and Fig. 5E, the authors have confirmed that the two pictures indeed have the problems of duplication. The authors reported that this problem came from the authors’ unintentional behavior, which may be due to a copy and paste error in the manner of image processing. The authors sincerely apologize for the inconvenience caused to our Editors and readers. Due to this duplication error, the authors and Editor have made the decision to retract this paper.

Preoperative Systemic Immune–Inflammation Index (SII) as a Superior Predictor of Long-Term Survival Outcome in Patients With Stage I–II Gastric Cancer After Radical Surgery

BackgroundSystemic immune–inflammation index (SII), calculated by immunoinflammatory cell counts of peripheral blood, is considered a predictor of survival outcome in several solid tumors, including gastric cancer (GC). However, there is no study focusing on the prognostic value of SII in the early stage of GC. This study aims to compare prognostic prediction capabilities of several inflammatory indices, nutritional indices, and tumor markers to further verify the superior prognostic value of SII in stage I–II GC patients after surgery.MethodsIn this study, 548 patients (358 in the training group and 190 in the validation group) with stage I–II GC after radical surgery were retrospectively analyzed. The peripheral blood indices of interest were SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), advanced lung cancer inflammation index (ALI), systemic inflammation score (SIS), prognostic nutritional index (PNI), body mass index (BMI), albumin, carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate-associated antigen 19-9 (CA19-9), and alpha-fetoprotein (AFP). The time-dependent receiver operating characteristic (t-ROC) curves and the area under the curve (AUC) were used to determine the optimal cutoff value and prognostic ability of each parameter. Kaplan–Meier curves and multivariable Cox regression models were used to evaluate independent prognostic factors. The nomogram was constructed based on the result of bidirectional stepwise regression model.ResultsThe optimal cutoff value of SII was 508.3. The 5-year overall survival rate of the low SII (SII-L) group was significantly higher than that of the high SII (SII-H) group (92% vs. 80%, P < 0.001), especially in the elderly and stage II patients (91% vs. 73%, P = 0.001; 86% vs. 67%, P = 0.003, respectively). The significant prognostic values of SII were consistent in most subgroups. In multivariate analysis, SII and CA19-9 were the only two independent prognostic hematology indices. The AUC value of SII (0.624) was greater than that of CA19-9 (0.528) and other prognostic parameters. Adding SII to the conventional model improved the predictive ability of 5-year overall survival as shown by the significantly increased net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (P = 0.033, P = 0.053, respectively) and modestly improved consistency index (C-index) (increased by 1.6%). External validation of SII-based nomogram demonstrated favorable predictive performance and discrimination. In addition, interactive web dynamic nomogram was published to facilitate clinical use.ConclusionSII is a simple but powerful index with a high predictive value to predict survival outcome in patients with stage I–II GC after radical operation. The SII-based nomogram can provide intuitive and accurate prognosis prediction of individual patients.

Laparoscopic vs open total gastrectomy for advanced gastric cancer following neoadjuvant therapy: A propensity score matching analysis

BACKGROUNDLaparoscopic total gastrectomy (LTG) has drawn increasing attention over the years. Although LTG has shown surgical benefits compared to open TG (OTG) in early stage gastric cancer (GC), little is known about the surgical and oncological outcomes of LTG for advanced GC following neoadjuvant therapy (NAT).AIMTo compare the long- and short-term outcomes of advanced GC patients who underwent LTG vs OTG following NAT.METHODSAdvanced GC patients who underwent TG following NAT between April 2011 and May 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences were enrolled and stratified into two groups: LTG and OTG. Propensity score matching analysis was performed at a 1:1 ratio to overcome possible bias.RESULTSIn total, 185 patients were enrolled (LTG: 78; OTG: 109). Of these, 138 were paired after propensity score matching. After adjustment for propensity score matching, baseline parameters were similar between the two groups. Compared to OTG, LTG was associated with a significantly shorter length of hospital stay (P = 0.012). The rates of R0 resection, lymph node harvest, and postoperative morbidity did not significantly differ between the two groups. Overall survival (OS) outcomes were comparable between the two groups. Pathological T and N stages were found to be independent risk factors for OS.CONCLUSIONLTG can be a feasible method for advanced GC patients following NAT, as it appears to be associated with better short- and comparable long-term outcomes compared to OTG.

Evaluation of PARP-1 by immunohistochemistry in a sample of Iraqi patients with gastric cancer

PARP-1 is a protein enzyme with a major role in DNA repair that is overexpressed in many malignancies. It is correlated with susceptibility and metastasis to lymph nodes in gastric cancer (GC). The objective of the present investigation is to estimate PARP1 expression in patients with gastric cancer and detected if it could be used as a predictive marker. Furthermore, we aimed to find the correlation between PARP1 expression and clinicopathological parameters, such as gender, age, invasion depth, histopathological type, involvement of lymph nodes, grade, and stages of GC. This is a retrospective study from the period 2018-2020. Fifty randomly selected subjects (10 normal and 40 GC) were examined for formalin-fixed, paraffin-embedded blocks (FFPE) of stomach tissue . The diagnosis reports were collected from the Pathology Department of the Gastroenterology and Hepatology Teaching Hospital and some private hospitals in Baghdad, Iraq. Hematoxylin and eosin (H&amp;E) and immunohistochemical (IHC) staining of PARP1 were applied for the histological sections. Statistical analysis was accomplished by SPSS system at P&lt;0.05. There were significant differences between the patients and control groups in the expression level of PARP1. There were also significant correlations between PARP1 expression and each of the histopathological subtype, grade, invasion depth, involvement of lymph node, and stages in patients. However, non- significant associations were found between the expression and the age and gender of patients. These results indicate that PARP1 could be employed as a good prospective marker for gastric cancer.

Chinese experts consensus on standardized surgical management of specimens from radical gastrectomy (2022 edition)

In the standardized diagnosis and treatment process of advanced gastric cancer, there is a unappreciated key link between standard radical surgery and accurate pathological reports. That is, the process of dissection, fixation, sampling and recording of the specimen by the surgeons, starting from specimen isolation to the management of the pathologist. Standardizing this process can not only accurately reflect the detailed distribution and exact number of lymph nodes, but also clarify the pathological stage of gastric cancer, so as to make adjuvant treatment plans. Moreover, it can also reflect the scope of intraoperative lymph node dissection to ensure the standardized implementation of surgery, including the overall dissection principle (en bloc resection), and therefore can provide a solid foundation for later related researches. So far, there is still a lack of complete and unified standard for the surgical management of specimens after radical gastrectomy in China. On the basis of the relevant researches and clinical practice about specimen management at home and abroad, the Chinese Journal of Gastrointestinal Surgery, in the name of the Gastric Cancer Professional Committee, Chinese Anticancer Association, as well as the Oncogastroenterology Professional Committee, Chinese Anticancer Association, organized dozens of experts to formulate a consensus on the standardized surgical management of specimens after repeated discussions and revisions for two years. This consensus is aimed to standardize the preparations, basic requirements and sample processing procedures before the surgical treatment of postoperative specimens after a radical surgery for gastric cancer patients, including the processing time of specimens, the processing and data archiving of gastric specimens, and lymph node grouping, sorting and fine sorting records, etc and with the purpose of standardizing the surgical treatment of postoperative specimens on the basis of standardized diagnosis and treatment of gastric cancer, in order to further promote the high-quality development of gastric cancer surgery in China.

Downregulation of LOC441461 Promotes Cell Growth and Motility in Human Gastric Cancer.

Simple SummaryLong noncoding RNAs (lncRNAs) are important regulators of cell progression or regression in gastric cancer (GC). The lncRNA LOC441461 was downregulated in TNM stage IV GC. The downregulation of LOC441461 promoted the proliferation, cell cycle progression, and metastasis of GC cells in vitro. We confirmed, with predictable targets, that LOC441461 interacts with transcription factors and promotes tumor progression. Our study suggests LOC441461 as a potential biomarker, which could also lead to a therapeutic target in patients with advanced TNM stage gastric cancer.Gastric cancer is a common tumor, with a high mortality rate. The severity of gastric cancer is assessed by TNM staging. Long noncoding RNAs (lncRNAs) play a role in cancer treatment; investigating the clinical significance of novel biomarkers associated with TNM staging, such as lncRNAs, is important. In this study, we investigated the association between the expression of the lncRNA LOC441461 and gastric cancer stage. LOC441461 expression was lower in stage IV than in stages I, II, and III. The depletion of LOC441461 promoted cell proliferation, cell cycle progression, apoptosis, cell motility, and invasiveness. LOC441461 downregulation increased the epithelial-to-mesenchymal transition, as indicated by increased TRAIL signaling and decreased RUNX1 interactions. The interaction of the transcription factors RELA, IRF1, ESR1, AR, POU5F1, TRIM28, and GATA1 with LOC441461 affected the degree of the malignancy of gastric cancer by modulating gene transcription. The present study identified LOC441461 and seven transcription factors as potential biomarkers and therapeutic targets for the treatment of gastric cancer.

The Value of Gastric Cancer Staging by Endoscopic Ultrasonography Features in the Diagnosis of Gastroenterology.

This research was aimed at exploring the application value of endoscopic ultrasonography (EUS) in the diagnosis of gastric cancer staging and the correlation between staging and clinical features of gastric cancer. A total of 72 patients with gastric cancer were selected and randomly divided into two groups. The patients in the pathological group underwent postoperative pathological examination, while those in the EUS group received preoperative EUS examination. The results showed that the staging accuracy of EUS was 73.33% for T1, 78.57% for T2, 27% for T3, and 100% for T4, compared with the pathological staging. The accuracy of N- and N+ was 42.5% and 82.3% in EUS, respectively, and the total accuracy was 55.7%. There was no considerable difference in the accuracy of T staging between early gastric cancer and advanced gastric cancer (P > 0.05), but there was a considerable difference in N staging (P < 0.05). Lymph node metastasis affected the accuracy of N staging (P < 0.05). The number and location of metastatic lymph nodes did not affect the judgment of metastatic lymph nodes (P > 0.05). In addition, the proportion of understaging and overstaging was greatly different among different lesion sizes and histological types of gastric cancer (P < 0.05). To sum up, the accuracy of EUS for T and N staging of gastric cancer needed to be improved. The location of gastric cancer lesions affected the accuracy of T staging, while the depth of invasion and lymph node metastasis affected the accuracy of N staging.

Increasing frequency of gene copy number aberrations is associated with immunosuppression and predicts poor prognosis in gastric adenocarcinoma.

Patients with Epstein-Barr virus-positive gastric cancers or those with microsatellite instability appear to have a favourable prognosis. However, the prognostic value of the chromosomal status (chromosome-stable (CS) versus chromosomal instable (CIN)) remains unclear in gastric cancer. Gene copy number aberrations (CNAs) were determined in 16 CIN-associated genes in a retrospective study including test and validation cohorts of patients with gastric cancer. Patients were stratified into CS (no CNA), CINlow (1-2 CNAs) or CINhigh (3 or more CNAs). The relationship between chromosomal status, clinicopathological variables, and overall survival (OS) was analysed. The relationship between chromosomal status, p53 expression, and tumour infiltrating immune cells was also assessed and validated externally. The test and validation cohorts included 206 and 748 patients, respectively. CINlow and CINhigh were seen in 35.0 and 15.0 per cent of patients, respectively, in the test cohort, and 48.5 and 20.7 per cent in the validation cohort. Patients with CINhigh gastric cancer had the poorest OS in the test and validation cohorts. In multivariable analysis, CINlow, CINhigh and pTNM stage III-IV (P < 0.001) were independently associated with poor OS. CIN was associated with high p53 expression and low immune cell infiltration. CIN may be a potential new prognostic biomarker independent of pTNM stage in gastric cancer. Patients with gastric cancer demonstrating CIN appear to be immunosuppressed, which might represent one of the underlying mechanisms explaining the poor survival and may help guide future therapeutic decisions.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined with Surgery: A 12-Year Meta-Analysis of this Promising Treatment Strategy for Advanced Gastric Cancer at Different Stages.

This meta-analysis was designed to systematically assess the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) combined with surgery for different stages of advanced gastric cancer (AGC) during the last 12 years. The Cochrane Library, PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched online, and papers were retrieved from other sources. Next, randomized controlled trials (RCTs) and high-quality nonrandomized controlled trials (NRCTs) were selected for this analysis. The meta-analysis was conducted with RevMan5.4 software. The 10 RCTs and 13 NRCTs selected for the study included 1892 patients. The overall survival rates were higher in the HIPEC group at 1 year (risk ratio [RR], 0.52; P = 0.004) and 3 years (RR, 0.63; P < 0.00001) than in the control group for the patients without peritoneal cancer, and the HIPEC group had a significant reduction in the recurrence rate (RR, 0.60; p < 0.00001). Among the patients with peritoneal carcinomatosis (PC), the HIPEC group had significantly higher overall survival rates at 1 year (RR, 0.62; P = 0.00001), 2 years (RR, 0.85; P = 0.002), and 3 years (RR, 0.87; P = 0.0001), with an increase in the overall median survival time of 4.67 months. The two groups showed no statistically significant difference in terms of complications for patients with PC (RR, 1.03; P = 0.93) or without PC (RR, 1.15; P = 0.51). For local AGC without PC, standard surgery combined with prophylactic HIPEC could prolong survival and reduce the recurrence rate without more complications. The prognosis of this treatment strategy for patients with PC is closely related to patient selection. Complete cytoreduction combined with therapeutic HIPEC could prolong survival.

Identification of Combinations of Plasma lncRNAs and mRNAs as Potential Biomarkers for Precursor Lesions and Early Gastric Cancer.

Patients with gastric cancer (GC) are usually first diagnosed at an advanced stage due to the absence of obvious symptoms at an early GC (EGC) stage. Therefore, it is necessary to identify an effective screening method to detect precursor lesions of GC (PLGC) and EGC to increase the 5-year survival rate of patients. Cell-free RNA, as a biomarker, has shown potential in early diagnosis, personalised treatment, and prognosis of cancer. In this study, six RNAs (CEBPA-AS1, INHBA-AS1, AK001058, UCA1, PPBP, and RGS18) were analysed via real-time quantitative polymerase chain reaction (RT-qPCR) using the plasma of patients with EGC and PLGC to identify diagnostic biomarkers. The receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic accuracy. Among the six RNAs, four lncRNAs (CEBPA-AS1, INHBA-AS1, AK001058, and UCA1) were upregulated and two mRNAs (PPBP and RGS18) were downregulated in the plasma of patients with PLGC and EGC. According to the findings of the ROC analysis, the four-RNA combination of INHBA-AS1, AK001058, UCA1, and RGS18 had the highest area under the curve (AUC) value for determining risk of GC in patients with PLGC and the six-RNA combination including CEBPA-AS1, INHBA-AS1, AK001058, UCA1, PPBP, and RGS18 had the highest AUC value for determining the risk of GC in patients with EGC. The results suggest the potential usefulness of noninvasive biomarkers for the molecular diagnosis of GC at earlier stages.