Risk and Prognosis of Subsequent Primary Gastric Cancer

Introduction: The incidence and prognostic impact of subsequent primary gastric cancer (GC) in a population of other cancer survivors is unclear. We aimed to evaluate susceptibility to subsequent primary GC in cancer survivors and prognosis of GC with prior cancer history. Methods: 2,211 and 23,416 GC cases with and without prior cancer history were retrospectively selected from the Surveillance, Epidemiology and End Results (SEER) database. Potential risk of developing subsequent primary GC was assessed through standardized incidence ratios (SIRs). Cox regression were adopted to analyze the influence of prior cancer history and clinical characteristic factors on the prognosis of subsequent primary GC. A nomogram was established to predict overall survival (OS). Propensity score matching (PSM) was conducted to eliminate possible bias. Results: Compared with general population, cancer survivors had an increased risk of subsequent primary GC (SIR 1.17, 95% CI 1.15-1.20, P<0.05). Prior cancer history was related to poor OS of GC [adjusted hazard ratio (aHR) 1.12, 95% CI 1.06-1.19, P<0.001], but not cancer-specific survival (aHR 0.97, 95% CI 0.89-1.05, P=0.441). In addition, age, grade, stage, year of diagnosis, surgery, TNM stage and tumor size were independent prognostic factors for OS in GC cases with prior cancers. The concordance index of the nomogram was 0.72 (95% CI 0.71-0.74), and calibrate curves showed good agreement between prediction by the nomogram and actual observation. Conclusions: Cancer survivors with increased risk of developing subsequent primary GC should strengthen their monitoring and follow-up to prevent occurrence of subsequent primary gastric cancer.

Haploinsufficiency by minute MutL homolog 1 promoter DNA methylation may represent unique phenotypes of microsatellite instability-gastric carcinogenesis

Promoter DNA methylation of MutL homolog 1 (MLH1) is considered to play a causative role in microsatellite instability (MSI) carcinogenesis in primary gastric cancer, and a high MSI status is associated with treatment sensitivity to human cancers. Nevertheless, clinicopathological analysis is defective for MLH1 methylation status in a quantitative manner. We newly developed quantitative methylation specific PCR using a TaqMan probe and applied it to 138 patients with primary gastric cancer who underwent gastrectomy in addition to basic molecular features such as MSI, Epstein Barr virus, and other DNA methylation status. (1) In primary gastric cancer, median methylation value was 0.055, ranging from 0 to 124.3. First, MLH1 hypermethylation was strongly correlated with MSI-High/MSI-Low status and suppressed immunostaining (P < 0.0001). (2) The MLH1 hypermethylation was associated with advanced age (P = 0.0048), antral location (P = 0.0486), synchronous multiple gastric cancer (P = 0.0001), and differentiated histology (P = 0.028). (3) Log-rank plot analysis identified the most relevant cut-off value (0.23) to reflect gentle phenotypes in MLH1 hypermethylation cases (P = 0.0019), especially in advanced gastric cancer (P = 0.0132), which are designated as haploinsufficiency of MSI (MSI-haplo) phenotype in this study. (4) In synchronous multiple gastric cancer, MLH1 hypermethylation was not necessarily confirmed as field cancerization. (5) MSI-haplo defined by MLH1 methylation status represented distinct prognostic phenotype even after molecular classifications. MLH1 hypermethylation designated as MSI-haplo may represent unique prognostic phenotype during gastric carcinogenesis.

Study on the Differential Value of Tumor Marker CA724 on Primary Gastric Cancer

We investigated the diagnostic value of the tumor marker CA724 in patients with primary gastric cancer. One hundred forty-six patients with primary gastric cancer were selected as the observation group; 89 patients with gastritis treated in the same period were included in the control group 1; 91 patients with healthy physical examination during the same period were included in the control group 2. Electrochemiluminescence immunoassay was used to determine the level of carbohydrate antigen CA724 in each group; the pathological data of the observation group were consulted, and the expression level of tumor marker CA724 under different pathological conditions was analyzed; ROC curve was drawn to evaluate the diagnostic value of CA724 in gastric cancer and gastritis. The level of CA724 in primary gastric cancer patients was significantly correlated with tumor diameter, tumor stage, differentiation type, and lymph node metastasis. The ROC curve was drawn with a CA724 cutoff value of 7.94 U/Ml. The AUC value of CA724 in primary gastric cancer patients was 0.815, with a diagnostic sensitivity of 84.68% and a specificity of 71.95%. In conclusion, CA724 was highly expressed in patients with primary gastric cancer, which can achieve the diagnostic differentiation of gastric cancer and gastritis, and obtain a high diagnostic efficiency, providing a reference basis for clinical diagnosis and treatment.

LncRNA HCP5 : A Potential Biomarker for Diagnosing Gastric Cancer

BackgroundIt has been reported that long non-coding RNAs (lncRNAs) can be regarded as a biomarker and had particular clinical significance for early screening and gastric cancer (GC) diagnosis. Therefore, this study aimed to investigate whether serum HCP5 could be a new diagnostic biomarker.MethodsFiltered out the HCP5 from the GEO database. The specificity of HCP5 was verified by real-time fluorescence quantitative PCR (qRT-PCR), and then the stability of HCP5 was verified by room temperature storage and repeated freeze-thaw experiments. Meanwhile, the accuracy of HCP5 was verified by agarose gel electrophoresis (AGE) and Sanger sequencing. Simultaneously, the expression level of serum HCP5 was detected by qRT-PCR in 98 patients with primary gastric cancer, 21 gastritis patients, 82 healthy donors, and multiple cancer types. Then, the methodology analysis was carried on. Moreover, receiver operating characteristic (ROC) was used to evaluate its diagnostic efficiency.ResultsqRT-PCR method had good repeatability and stability in detecting HCP5. The expression level of HCP5 in the serum of gastric cancer patients was remarkably higher than that of healthy controls, and it could distinguish gastritis patients from healthy donors. Besides, the expression of HCP5 was increased dramatically in MKN-45 and MGC-803. The FISH assay showed that HCP5 was mainly distributed in the cytoplasm of MKN-45 and BGC-823 cells. When HCP5 was combined with existing tumor markers, the diagnostic efficiency of HCP5 was the best, and the combined diagnosis of carcinoembryonic antigen (CEA), carbohydrate antigen199 (CA199), and HCP5 can significantly improve the diagnostic sensitivity. Besides, compared with the expression levels of thyroid cancer (THCA), colorectal cancer (CRC), and breast cancer (BRCA), serum HCP5 in gastric cancer was the most specific. Moreover, the high expression of serum HCP5 was related to differentiation, lymph node metastasis, and nerve invasion. The term of serum HCP5 after the operation was significantly lower than that of patients with primary gastric cancer.ConclusionSerum HCP5 can be used as a potential biomarker of non-invasive fluid biopsy, which had a unique value in the early diagnosis, development, and prognosis of gastric cancer.

The Research and Analysis of Bring Perigastric Tumor Deposits into The Staging of Primary Gastric Cancer

Background: The current significance of perigastric tumor deposits (TDs) in gastric cancer (GC) for indicating prognosis remains unclear. The aim of this study was to assess the prognostic value of perigastric TDs and a new TNM staging involving TDs for GC.Methods: The pathological data of 6672 patients with GC who underwent gastrectomy or operation of gastric cancer with other diseases between January 1, 2012 and December 31, 2017 at Chinese PLA General Hospital were analyzed retrospectively. The patients were divided into tumor deposits positive (TD+) group and tumor deposits negative (TD-) group. The differences between TD+ and TD- were analyzed by binary Logistic regression model. To draw survival curves, we used Kaplan-Meier methods. Multivariate Cox regression model and Log-rank test was used to analyze the data.Results: Perigastric TDs were found to be positive in 339 (5.09%) of the 6672 patients with GC of which 237 were males (69.91%) and 102 females (30.09%) (2.32:1). The median age was 59 years (ranging from 27 to 78 years). No significant differences were detected between the two groups. Univariate and multivariate survival analysis both indicated that GC patients with positive TDs had poorer prognosis than those with negative TDs (p<0.05). The 1-, 3-and 5-year overall survival rates of GC patients with TDs were 68.3%, 19.6%, and 11.2%, respectively, and were significantly poorer than those of the staged matched control group. There was statistical significance between the location of TDs and patient survival in patients with gastric cancer (p＜0.05). A new TNM staging was formulated according to the TDs location. When TDs appear on the gastric body, the original T1, T2, T3 stages change to T4a, and T4a, T4b change to T4b; when TDs appear in the lesser curvature, the previous N0, N1, N2, N3 stage change to N3; when the TDs located in the greater curvature or the distant tissue, the patient should be categorized as M1. After using the new stage, the survival curve of patients with TDs was closer to that of patients without TDs in each pTNM staging.Conclusion: 1. Tumor deposits is a bad prognostic factor in patients with primary gastric cancer. 2. The location of tumor deposits is associated with the prognosis of patients with primary gastric cancer. 3. The new stage is more suitable for patients with tumor deposits of gastric cancer.