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While genetic alterations in several regulators of the cell cycle have a significant impact on the gastric carcinogenesis process, the prognostic role of them remains to be further elucidated. The TCGA-STAD training set were downloaded and the mRNA expression matrix of cell cycle genes was extracted and corrected for further analysis after taking the intersection with GSE84437 dataset. Differentially expressed mRNAs were identified between tumor and normal tissue samples in TCGA-STAD. Univariate Cox regression analysis and lasso Cox regression model established a novel seven-gene cell cycle signature (including GADD45B, TFDP1, CDC6, CDC25A, CDC7, SMC1A and MCM3) for GC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was found to be an independent prognostic factor for GC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. The signature was further validated in the GSE84437 dataset. In tissue microarray, CDC6 and MCM3 protein expression were significant differences by the immunohistochemistry-based H-score between tumor tissues and adjacent tissues, and CDC6 is an independent prognostic factor for GC. Interestingly, our GSEA revealed that low-risk patients were more related to cell cycle pathways and might benefit more from therapies targeting cell cycle. Our study identified a novel robust seven-gene cell cycle signature for GC prognosis prediction that may serve as a beneficial complement to clinicopathological staging. The signature might provide potential biomarkers for the application of cell cycle regulators to therapies and treatment response prediction.

In China, it has been well recognized that some female patients with esophageal squamous cell carcinoma (ESCC) have different overall survival (OS) time, even with the same tumor-node-metastasis (TNM) stage, challenging the prognostic value of the TNM system alone. An effective predictive model is needed to accurately evaluate the prognosis of female ESCC patients.To construct a novel prognostic model with clinical and reproductive data for Chinese female patients with ESCC, and to assess the incremental prognostic value of the full model compared with the clinical model and TNM stage.A new prognostic nomogram incorporating clinical and reproductive features was constructed based on univariatie and Cox proportional hazards survival analysis from a training cohort (A clinical-reproductive model including incidence area, age, tumor differentiation, lymph node metastasis (N) stage, estrogen receptor alpha (ESR1) and beta (ESR2) expression, menopausal age, and pregnancy number was constructed to predict OS in female ESCC patients. Compared to the clinical model and TNM stage, the time-dependent ROC and C-index of the clinical-reproductive model showed a good discriminative ability for predicting 1-, 3-, and 5-years OS in the primary training, internal and external validation sets. Based on the optimal cut-off value of total prognostic scores, patients were classified into high- and low-risk groups with significantly different OS. The estrogen response was significantly associated with p53 and apoptosis pathways in esophageal cancer.The clinical-reproductive prognostic nomogram has an incremental prognostic value compared with the clinical model and TNM stage in predicting OS in Chinese female ESCC patients.

BackgroundThis study was intended to construct a brand new prognostic nomogram after combine clinical and pathological characteristics to increases prognostic value in patients with esophageal squamous cell carcinoma.MethodsA total of 1,634 patients were included. Subsequently, the tumor tissues of all patients were prepared into tissue microarrays. AIPATHWELL software was employed to explore tissue microarrays and calculate the tumor-stroma ratio. X-tile was adopted to find the optimal cut-off value. Univariate and multivariate Cox analyses were used to screen out remarkable characteristics for constructing the nomogram in the total populations. A novel prognostic nomogram with clinical and pathological characteristics was constructed on the basis of the training cohort (n=1,144). What’s more performance was validated in the validation cohort (n=490). Clinical-pathological nomogram were assessed by concordance index, time-dependent receiver operating characteristic, calibration curve and decision curve analysis.ResultsThe patients can divide into two groups with cut-off value of 69.78 for the tumor-stroma ratio. It is noteworthy that the survival difference was noticeable (PPConclusionsAs evidently revealed by the research findings, tumor-stroma ratio is an independent prognostic factor in patients with esophageal squamous cell carcinoma. The clinical-pathological nomogram has an incremental value compared TNM stage in predicting overall survival.

BACKGROUND Primary small cell carcinoma of the esophagus (PSCE) is a highly invasive malignant tumor with a poor prognosis compared with esophageal squamous cell carcinoma. Due to the limited samples size and the short follow-up time, there are few reports on elucidating the prognosis of PSCE, especially on the establishment and validation of a survival prediction nomogram model covering general information, pathological factors and specific biological proteins of PSCE patients. AIM To establish an effective nomogram to predict the overall survival (OS) probability for PSCE patients in China. METHODS The nomogram was based on a retrospective study of 256 PSCE patients. Univariate analysis and multivariate Cox proportional hazards regression analysis were used to examine the prognostic factors associated with PSCE, and establish the model for predicting 1-, 3-, and 5-year OS based on the Akaike information criterion. Discrimination and validation were assessed by the concordance index (C-index) and calibration curve and decision curve analysis (DCA). Histology type, age, tumor invasion depth, lymph node invasion, detectable metastasis, chromogranin A, and neuronal cell adhesion molecule 56 were integrated into the model. RESULTS The C-index was prognostically superior to the 7th tumor node metastasis (TNM) staging in the primary cohort [0.659 (95%CI: 0.607-0.712) vs 0.591 (95%CI: 0.517-0.666), P = 0.033] and in the validation cohort [0.700 (95%CI: 0.622-0.778) vs 0.605 (95%CI: 0.490-0.721), P = 0.041]. Good calibration curves were observed for the prediction probabilities of 1-, 3-, and 5-year OS in both cohorts. DCA analysis showed that our nomogram model had a higher overall net benefit compared to the 7th TNM staging . CONCLUSION Our nomogram can be used to predict the survival probability of PSCE patients, which can help clinicians to make individualized survival predictions.

Purpose Some studies indicated that gender is associated with prognostic of cancer, However, currently the prognostic value of gender for gastric cardia adenocarcinoma (GCA) survival is unclear. The aim of our study is to reveal the influence of gender on the prognosis of patients with GCA. Patients and methods A total of 42,345 cases Chinese GCA patients were enrolled from our previously established GCA and esophageal cancer databases. The clinicopathological characteristics were retrieved from medical records in hospital. The follow-up was performed through letter, telephone or home interview. Among GCA patients, there were 32,544 (76.9%) male patients with the median age 62 years (range 17–97) and 9,801 (23.1%) female patients with the median age 61 years (range 17–95 years). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival. Cox proportional hazards model was used for competing risk analyses, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated. Results Men had shorter GCA-specific survival than women by multivariate analysis (HR 1.114; 95% CI 1.061 to 1.169; P vs. male, P vs. male, P vs. male, P = 0.035). It was worth noting that in patients with stages I, II, III, and IV, female patients survive longer than male patients (P = 0.049; P = 0.011; P P = 0.044, respectively). Conclusion Gender is an independent prognostic factor for patients with GCA. In comparison with men, women have a significantly better outcome. Smoking and drinking may be protective factors for male GCA patients.

Riboflavin is an essential micronutrient for normal cellular growth and function. Lack of dietary riboflavin is associated with an increased risk for esophageal squamous cell carcinoma (ESCC). Previous studies have identified that the human riboflavin transporter SLC52A3a isoform (encoded by SLC52A3) plays a prominent role in esophageal cancer cell riboflavin transportation. Furthermore, SLC52A3 gene single nucleotide polymorphisms rs3746804 (T>C, L267P) and rs3746803 (C >T, T278M) are associated with ESCC risk. However, whether SLC52A3a (p.L267P) and (p.T278M) act in riboflavin transportation in esophageal cancer cell remains inconclusive. Here, we constructed the full-length SLC52A3a protein fused to green fluorescent protein (GFP-SLC52A3a-WT and mutants L267P, T278M, and L267P/T278M). It was confirmed by immunofluorescence-based confocal microscopy that SLC52A3a-WT, L267P, T278M, and L267P/T278M expressed in cell membrane, as well as in a variety of intracellular punctate structures. The live cell confocal imaging showed that SLC52A3a-L267P and L267P/T278M increased the intracellular trafficking of SLC52A3a in ESCC cells. Fluorescence recovery after photobleaching of GFP-tagged SLC52A3a meant that intracellular trafficking of SLC52A3a-L267P and L267P/T278M was rapid dynamics process, leading to its stronger ability to transport riboflavin. Taken together, the above results indicated that the rs3746804 (p.L267P) polymorphism promoted intracellular trafficking of SLC52A3a and riboflavin transportation in ESCC cells.

Quinoa is a good gluten-free resource for food processing, especially bread making, and can improve and prevent the development of complications associated with celiac disease (CD). However, lack of gluten affects quinoa bread quality. Previous research showed that soy protein isolate (SPI) could improve gluten-free bread quality to some extent. Therefore, this study investigated the effects of SPI on the physical properties of quinoa dough and gluten-free bread quality characteristics.Results showed that, with appropriate SPI substitution, the farinograph properties of quinoa flour significantly improved (P 0.05). The sample with 8% SPI substitution showed a better development time (DT, 3.30 ± 0.20 min), stability time (ST, 8.80 ± 0.10 min) and softening degree (SD, 8.80 ± 0.10 FU), which were close to those of wheat flour, although more water absorption (WA, 76.40 ± 2.10%) was needed than for wheat flour (66.30 ± 3.10%). The extensograph properties of quinoa flour also significantly improved after 8% SPI substitution (P 0.05). Furthermore, SPI substitution increased G' moduli of quinoa dough and decreased tan δ to some extent, providing better rheological properties closer to those of wheat dough. SPI substitution also improved the quality and texture of quinoa bread and reduced the gap with wheat bread. When SPI substitution was 8%, the specific volume, hardness and springiness of quinoa bread were 2.29 ± 0.05 mL gThese results suggested that SPI substitution would be an effective way to develop higher-quality gluten-free bread. © 2022 Society of Chemical Industry.

Owing to the measurement difficulty and the required time needed to analyze wear processes of ball screws, very few studies have been reported. Here, on the basis of a test bench and a Taylor Hobson surface profilometer, the measuring procedure for the raceway surface profiles of ball screws was proposed first. Then the raceway surface profiles of a typical ball screw were measured after 1.42 million running revolutions. Finally, a combinational method including the statistical parameters, recurrence analysis, and fractal dimensional was used to characterize the lubricated wear process. Results show that the increase of the surface roughness (Ra) and maximum peak-to-valley height (Rz) can be up to 396% and 395%, the recurrence rate can decrease more than 59%, and the ratio between the minimum and maximum values of the fractal dimension can be 77% after 1.42 million running revolutions. Further analysis showed that the three methods all reflected the raceway wear dependence on the number of revolutions, and the linear correlation of the fractal dimension method with the number of revolutions was the strongest, which provides a new way to predict the wear states of ball screws by monitoring the worn states of the raceway surface profiles.

POLE mutations, which lead to an ultramutated phenotype in colorectal cancer (CRC), have been reported as a promising marker in immunotherapy. We performed sequencing of CRC cases in Zhejiang University (ZJU) and extracted obtainable data from recently published results, including The Cancer Genome Atlas (TCGA), Japanese studies and clinical trials, to present clinical patterns of POLE driver‐mutated CRC and reveal its heterogeneity. The rate of somatic POLE driver mutations has been reported as 2.60% (ZJU cohort), 1.50% (TCGA cohort), 1.00% (Japan cohort), and 1.00% (Lancet cohort). POLE driver mutations show a clearly increased mutation burden (mean TMB: 217.98 mut/Mb in ZJU; 203.13 mut/Mb in TCGA). Based on pooled data, more than 70.00% of patients with POLE driver mutations were diagnosed before they were 55 years old and at an early disease stage (Stage 0–II >70.00%), and more than 70.00% were male. Among Asian patients, 68.40% developed POLE driver mutations in the left‐side colon, whereas 64.00% of non‐Asian patients developed them in the right‐side colon (p, POLE could be a promising marker for immunotherapy, and its heterogeneity should not be ignored. Here we present the clinical patterns and heterogeneity of POLE driver mutations so that investigators and physicians will be better equipped to design clinical trials and analyze their data.

Background/purpose Genioplasty were used widely to correct chin deformities. The purpose of this study was to design and manufacture a dental-supported surgical guide for genioplasty surgery and assess for surgical accuracy. Materials and methods eleven patients with chin deformities were treated in this study. The computed tomography (CT) data of the patient's skull and the digital dental models of stone dental models were acquired preoperatively. For each patient, a virtual three-dimensional (3D) model of the skull was constructed and enhanced with digital dental models. A surgical simulation was then performed using computer-aided surgical simulation (CASS) technology based on clinical examination and 3D cephalometry. The surgery was simulated preoperatively which allowed the design of a cutting guide and a dental-supported repositioning guide for genioplasty, which was then 3D-printed and used during operation after disinfection. After surgery, the outcome was evaluated by superimposing the postoperative CT model onto the preoperative model, recording the linear and angular deviation of landmarks and plane, then measuring the differences between the planned and actual outcomes. Results The osteotomy and repositioning were successfully performed as planned using surgical guides. No inferior alveolar nerve damage was seen in this study. The dental-supported surgical guide showed excellent accuracy, with the largest differences between the planned and the postoperative chin segment being 0.9 mm and 3.2°. Conclusion The dental-supported surgical guide designed preoperatively provided a reliable method of transfer genioplasty planning. This can assist surgeons in accurately performing osteotomy and repositioning bone segments during a genioplasty.

Circular RNAs (circRNAs) play important roles in cancer progression. hsa_circRNA6448-14 originates from exon 5 to exon 11 of the TGFBI gene. We investigated the roles of hsa_circRNA6448-14 in esophageal squamous cell carcinoma (ESCC) with microarrays and quantitative real-time polymerase chain reaction (qRT-PCR), Kaplan-Meier analysis, loss-of-function and gain-of-function assays, and pull-down assays for miRNA binding. The hsa_circRNA6448-14-miRNA-mRNA network was drawn using Circos. hsa_circRNA6448-14 was significantly upregulated in ESCC tissues and cell lines. As a diagnostic biomarker, hsa_circRNA6448-14 had an area under the curve (AUC), sensitivity, and specificity of 0.906, 82.9%, and 85.5%, respectively. hsa_circRNA6448-14 upregulation was correlated with poor differentiation, advanced pTNM stage, poor disease-free survival (DFS), and poor overall survival (OS). Elevated hsa_circRNA6448-14 promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro. hsa_circRNA6448-14 functioned as a miRNA sponge to competitively bind miR-455-3p, and hsa_circRNA6448-14 expression negatively correlated with that of miR-455-3p. hsa_circRNA6448-14 promoted carcinogenesis in ESCC, suggesting that hsa_circRNA6448-14 could serve as a diagnostic and prognostic biomarker for ESCC.

Background: Preoperative assessment of patients is meaningful to predict survival in patients with malignant tumors. The prognostic nutritional index (PNI) is one of the most significant factors re...

Esophageal squamous cell carcinoma (ESCC) is one of the most common aggressive malignancies worldwide, particularly in northern China. The absence of specific early symptoms and biomarkers leads to late-stage diagnosis, while early diagnosis and risk stratification are crucial for improving overall prognosis. We performed UPLC-MS/MS on 450 ESCC patients and 588 controls consisting of a discovery group and two validation groups to identify biomarkers for early detection and prognosis. Bioinformatics and clinical statistical methods were used for profiling metabolites and evaluating potential biomarkers. A total of 105 differential metabolites were identified as reliable biomarker candidates for ESCC with the same tendency in three cohorts, mainly including amino acids and fatty acyls. A predictive model of 15 metabolites [all-trans-13,14-dihydroretinol, (±)-myristylcarnitine, (2S,3S)-3-methylphenylalanine, 3-(pyrazol-1-yl)-L-alanine, carnitine C10:1, carnitine C10:1 isomer1, carnitine C14-OH, carnitine C16:2-OH, carnitine C9:1, formononetin, hyodeoxycholic acid, indole-3-carboxylic acid, PysoPE 20:3, PysoPE 20:3(2n isomer1), and resolvin E1] was developed by logistic regression after LASSO and random forest analysis. This model held high predictive accuracies on distinguishing ESCC from controls in the discovery and validation groups (accuracies > 89%). In addition, the levels of four downregulated metabolites [hyodeoxycholic acid, (2S,3S)-3-methylphenylalanine, carnitine C9:1, and indole-3-carboxylic acid] were significantly higher in early cancer than advanced cancer. Furthermore, three independent prognostic markers were identified by multivariate Cox regression analyses with and without clinical indicators: a high level of MG(20:4)isomer and low levels of 9,12-octadecadienoic acid and L-isoleucine correlated with an unfavorable prognosis; the risk score based on these three metabolites was able to stratify patients into low or high risk. Moreover, pathway analysis indicated that retinol metabolism and linoleic acid metabolism were prominent perturbed pathways in ESCC. In conclusion, metabolic profiling revealed that perturbed amino acids and lipid metabolism were crucial metabolic signatures of ESCC. Both panels of diagnostic and prognostic markers showed excellent predictive performances. Targeting retinol and linoleic acid metabolism pathways may be new promising mechanism-based therapeutic approaches. Thus, this study would provide novel insights for the early detection and risk stratification for the clinical management of ESCC and potentially improve the outcomes of ESCC.

BackgroundThis study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA.MethodsA total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan–Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA.ResultsThere were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P P P P ConclusionThoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary.

Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival.To investigate the clinical features and survival factors in Chinese patients with PMME.The clinicopathological findings of ten cases with PMME treated at Henan Provincial People's Hospital were summarized. Moreover, the English- and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival.A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients (55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients (36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis (LNM) was 51.2% (107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the pT stage [The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and pT stage are independent prognosis factors for OS, and the pT stage is the prognosis factor for DFS in patients with PMME.

BACKGROUND Gastric cardia adenocarcinoma (GCA), which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries, is of similar geographic distribution with esophageal squamous cell carcinoma in China, and even referred as "sister cancer" by Chinese oncologists. The molecular mechanism for GCA is largely unknown. Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers. However, the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis. AIM To characterize E-cadherin expression in normal gastric cardia mucosa, dysplasia and GCA tissues, and its influence on prognosis for GCA. METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases. The enrollment criteria included radical surgery for GCA, but without any radio- or chemo-therapy before operation. The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue (n = 208) and dysplasia lesions (n = 156) were collected, and processed as tissue microarray for immunohistochemistry. The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter, telephone or home interview. E-cadherin protein expression was determined by two step immunohistochemistry. Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients. RESULTS Of the 4561 GCA patients, there were 3607 males with a mean age of 61.6 ± 8.8 and 954 females with a mean age of 61.9 ± 8.6 years, respectively. With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA, the positive immunostaining rates for E-cadherin decreased significantly from 100% to 93.0% and 84.1%, respectively (R2 = 0.9948). Furthermore, E-cadherin positive immunostaining rate was significantly higher in patients at early stage (0 and I) than in those at late stage (II and III) (92.7% vs 83.7%, P = 0.001). E-cadherin positive expression rate was significantly associated with degree of differentiation (P = 0.001) and invasion depth (P < 0.001). Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative (P = 0.026). It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis. However, in patients with negative lymph node metastasis, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.036). Similarly, in patients with late stage GCA, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.011). CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

This article provides a method based on self-organizing maps (SOM) neural network clustering and support vector machine (SVM) ensembles to predict the survival risk levels of esophageal cancer. Nine blood indexes related to patient survival are found by using SOM clustering method. Two critical thresholds for survival are found by plotting the receiver operating characteristic (ROC) curve twice, and the lifetime is divided into three risk levels. Using the SVM method, patients' risk levels are predicted and assessed. Four kernel functions of SVM are compared, and the prediction effect of RBF kernel function is better than other kernel functions. The parameters of SVM are optimized by using genetic algorithm (GA), particle swarm algorithm (PSO) and artificial bee colony (ABC) algorithm. Experimental results show that the prediction accuracies are improved by using optimization algorithms. After comparison, ABC-SVM has better prediction results than GA-SVM and PSO-SVM with a high prediction rate and fast running time.

Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer (CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients. Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database (1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments (radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival. Results: Among the 500 CEC patients, 278 (55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients (99.2%) were diagnosed with squamous cell carcinoma. In 171 (34.2%) patients who received surgery, 22 (12.9%) had undergone laryngectomy. In 322 (64.4%) patients who received non-surgical treatments, 245 (76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy (P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.

Aim: To determine the prevalence of Helicobacter pylori infection and correlation between H. pylori infection and single nucleotide polymorphism (SNPs) identified in gastric cardia adenocarcinoma (GCA) patients. Methods: A case control study was performed. 22 risks of GCA-related SNPs were identified by genotyping assay and the relationship between susceptibility loci for GCA and H. pylori infection was further analyzed. Results: Helicobacter pylori infection was associated with GCA significantly (odds ratio: 1.40; 95% CI: 1.29–1.53 p

Abnormal long non-coding RNAs (lncRNAs) have been detected in esophageal squamous cell carcinoma (ESCC). Here, we focused on lncRNA ZNF667-AS1 and its downstream mechanism in ESCC progression. Differentially expressed lncRNAs in ESCC were predicted by bioinformatics analysis. ZNF667-AS1, microRNA-1290 (miR-1290), and prune homolog 2 with BCH domain (PRUNE2) expression was determined with their relationship in cell biological processes analyzed also by means of gain- and loss-of-function assays. Xenograft mouse models were performed to re-produce the in vitro findings. We found a decline in ZNF667-AS1 expression in ESCC tissues and cell lines. ZNF667-AS1 overexpression indicated a favorable prognosis of ESCC sufferers. ZNF667-AS1 overexpression suppressed ESCC cell malignant potentials. ZNF667-AS1 reduced miR-1290 to result in upregulation of the miR-1290 target gene PRUNE2. The inhibiting property of ZNF667-AS1 on the malignant characteristics of ESCC cells was achieved by disrupting the miR-1290-mediated downregulation of PRUNE2. ZNF667-AS1 suppressed the tumorigenesis of ESCC in vivo. Collectively, our study demonstrates that ZNF667-AS1 can function as a tumor suppressor in ESCC by upregulating PRUNE2 and downregulating miR-1290.

The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients., The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, the authors identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, as well as the potential associations of these alterations with prognosis and dietary habits.

Background POLE/POLD1 mutation leads to ultra-mutated phenotype in colorectal cancer (CRC) and could be a promising marker for immunotherapy. Methods We sequenced 338 CRC patients in Asian and obtained 284 white CRC patients from TCGA. Results The prevalence of POLE/POLD1 mutations were different in racial (6.51% vs 11.27%; P=0.036) (table 1). The right-sided colon shows the highest rate of POLE/POLD1 mutations in both group (50% vs 65.63%, P=0.251), while Asian has a higher rate in the left-sided colon than White (36.40% vs 9.38%, P=0.016). We further calculate the prevalence of POLE/POLD1 mutation in different primary sites which proved prevalence are different depending on race (10.35% Asian vs 1.51% White; P=0.027). Conclusions We firstly report primary sites and racial heterogeneity of POLE/POLD1 mutation in CRC to call for more attention when designing clinical trials and data analysis.

The diagnosis of the degree of differentiation of tumor cells can help physicians to make timely detection and take appropriate treatment for the patient's condition. In this study, the original dataset is clustered into two independent types by the Kohonen clustering algorithm. One type is used as the development sets to find correlation indicators and establish predictive models of differentiation, while the other type is used as the validation sets to test the correlation indicators and models. In the development sets, thirteen indicators significantly associated with the degree of differentiation of esophageal squamous cell carcinoma are found by the Kohonen clustering algorithm. Thirteen relevant indicators are used as input features and the degree of tumor differentiations is used as output. Ten classification algorithms are used to predict the differentiation of esophageal squamous cell carcinoma. Artificial bee colony-support vector machine (ABC-SVM) predicts better than the other nine algorithms, with an average accuracy of 81.5% for the 10-fold cross-validation. Based on logistic regression and ReliefF algorithm, five models with the greater merit for the degree of differentiation are found in the development sets. The AUC values of the five models are 0.672, 0.628, 0.630, 0.628, and 0.608 (P < 0.05). The AUC values of the five models in the validation sets are 0.753, 0.728, 0.744, 0.776, and 0.868 (P < 0.0001). The predicted values of the five models are constructed as the input features of ABC-SVM. The accuracy of the 10-fold cross-validation reached 82.0 and 86.5% in the development sets and the validation sets, respectively.

BACKGROUND Preoperative pulmonary function plays an important role in selecting surgical candidates and assessing postoperative complications. Reduced pulmonary function is associated with poor survival in several cancers, but the prognostic value of preoperative pulmonary function in esophageal squamous cell carcinoma (ESCC) is unclear. Nutritional and systemic inflammation parameters are vital to cancer survival, and the combination of these parameters improves the prognostic value. The hemoglobin, albumin, lymphocytes and platelets (HALP) score is a novel prognostic indicator to reflect the nutritional and inflammation status, but the clinical effects of the HALP score combined with maximal voluntary ventilation (MVV), an important parameter of pulmonary function, have not been well studied in ESCC. AIM To investigate the prognostic value of MVV and HALP score for assessing postoperative survival of ESCC patients. METHODS Data from 834 ESCC patients who underwent radical esophagectomy with R0 resection were collected and retrospectively analyzed. Preoperative MVV and HALP data were retrieved from medical archives. The HALP score was calculated by the formula: Hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). The optimal cut-off values of MVV and HALP score were calculated by the receiver operating characteristic curve analysis. The Kaplan-Meier method with log-rank test was used to draw the survival curves for the variables tested. Multivariate Cox proportional hazard regression models were used to analyze the independent prognostic factors for overall survival. RESULTS MVV was significantly associated with gender (P < 0.001), age at diagnosis (P < 0.001), smoking history (P < 0.001), drinking history (P < 0.001), tumor length (P = 0.013), tumor location (P = 0.037) and treatment type (P = 0.001). The HALP score was notably associated with gender (P < 0.001), age at diagnosis (P = 0.035), tumor length (P < 0.001) and invasion depth (P = 0.001). Univariate Cox regression analysis showed that low MVV and low HALP score were associated with worse overall survival (all P < 0.001). Multivariate analysis showed that low MVV and the HALP score were both independent risk factors for overall survival (all P < 0.001). The combination of MVV and HALP score improved the prediction performance for overall survival than tumor-node-metastasis. Also, low combination of MVV and HALP score was an independent risk factor for poor overall survival (P < 0.001). CONCLUSION MVV, HALP score and their combination are simple and promising clinical markers to predict overall survival of ESCC patients.