scholarly journals The clinical and prognostic significance of HER2 and Ki67 expression in 2062 Chinese patients with resectable gastric cancer: a retrospective study

2020 ◽  
Author(s):  
Wenfan Wang ◽  
Zhiqiang Chen ◽  
Qinghua Zhang ◽  
Yanjie You ◽  
Ailing Ma ◽  
...  

Abstract Background The purpose of this study was to assess the prognostic value of the expression of human epidermal growth factor receptor 2 (HER2), Ki67, and their combination levels in the prognosis of Chinese patients with resectable gastric cancer (GC). Methods A total of 2062 Chinese GC patients were recruited with HER2 and Ki67 expression being evaluated using immunohistochemistry. Patients were divided into four groups according to HER2 and Ki67 expression. The distributions between HER2 and Ki67 expression levels and clinicopathological characteristics were compared using the Chi-square test. The relationship between HER2 and Ki67 expression level and overall survival were evaluated with the univariate and multivariate Cox regression analysis. Results There was no statistical differences between the overall survival (OS) rate and the expression level of HER2 (P = 0.748) or Ki67 (P = 0.063), but there were significant relationships between the OS rates and the combining expression levels of HER2/Ki67 (P < 0.05). Further, Ki67, sex, T stage, N stage, TNM stage, and adjuvant chemotherapy were significant and independent risk factors for GC survival (P < 0.05). Conclusions Our study illustrated that Ki67, but not HER2 acted as an independent prognostic factor in Chinese resectable GC patients. The evaluation of the combining expression levels of HER2/Ki67 may be more useful to assess patient prognosis with resectable GC.

2020 ◽  
Author(s):  
Tailai An ◽  
Qian Liang ◽  
Tengfei Hao ◽  
Lingna Deng ◽  
Xiaofang Lu ◽  
...  

Introduction: ACP5 plays crucial roles in multiple pathological processes, including the genesis and progression of malignant tumors. We performed this study with the purpose of determining whether ACP5 is a crucial biomarker significantly related with prognoses of gastric cancer (GC) patients. Methods: The expression level of ACP5 level was assessed among 170 gastric cancer specimens using immunohistochemistry (IHC). The associations between ACP5 expression and clinicopathological variables were evaluated. Univariate and multivariate Cox regression analyses were performed to confirm independent prognostic factors for GC patients. Results: It was revealed that ACP5 expression level in gastric cancer tissue was significantly associated with depth of invasion (P=0.029), and TNM stage (P=0.036). ACP5 was demonstrated by multivariate Cox regression analysis to be an independent prognostic factor for overall survival (OS) (P=0.001) and recurrence-free survival (RFS) (P=0.011) of GC patients. Conclusions: The expression of ACP5 in GC tissue was significantly higher than that in normal tissues and its overexpression was associated with a poorer prognosis, suggesting its potential roles in preventing and treating GC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zongxian Zhao ◽  
Shuliang Li ◽  
Shilong Li ◽  
Jun Wang ◽  
Hai Lin ◽  
...  

Abstract Background Gastric cancer (GC) is one of the most common and fatal cancers worldwide. Effective biomarkers to aid the early diagnosis of GC, as well as predict the course of disease, are urgently needed. Hence, we explored the role and function of cadherin-6 (CDH6) in the diagnosis and prognosis of gastric cancer. Methods The expression levels of CDH6 in cancerous and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) dataset. The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and CDH6 expression were evaluated statistically, and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. 44 GC tissue samples, 20 donor-matched adjacent normal tissue samples, and associated detailed clinical information, were collected from the Tianjin Medical University General Hospital. CDH6 expression levels were determined for further validation. Results CDH6 was upregulated in GC samples compared to normal gastric tissue. Furthermore, GSEA identified the tricarboxylic acid (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism, oxidative phosphorylation, and the pentose phosphate pathway as differentially enriched in GC tissue samples. According to the area under the ROC curve (AUC) values (AUC = 0.829 in the TCGA and 0.966 in the GSE54129 dataset), CDH6 expression was associated with high diagnostic efficacy. Patients with high CDH6 levels in their GC tissues had a higher T number (according to the TNM classification) and a worse prognosis than those with low CDH6 expression. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). Conclusion CDH6 was upregulated in GC, and high CDH6 expression was indicative of a higher T number and a worse prognosis. Therefore, CDH6 represents a potentially independent molecular biomarker for the diagnostic and prognostic prediction of GC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanxia Zhang ◽  
Huiyun Wang ◽  
Yu Xia

Abstract Background The purpose of this study was to evaluate the diagnostic and prognostic significance of miR-211-5p in atherosclerosis (AS) by detecting the expression level in serum of patients with AS. Methods A total of 85 healthy controls and 90 asymptomatic AS patients participated in this study. The expression level of miR-211-5p in all subjects were measured by qRT-PCR. Spearman correlation coefficient was used to evaluate the correlation of miR-211-5p with CRP and CIMT. The ROC curve was established to assess the diagnostic value of miR-211-5p in AS. The Kaplan–Meier survival curve and multivariate COX regression analysis were used to evaluate the prognostic significance of miR-211-5p in AS. Results The expression levels of miR-211-5p in AS patients were significantly lower than in healthy controls (P < 0.001), and miR-211-5p showed a significant negative correlation with CRP (r =  − 0.639, P < 0.001) and CIMT (r =  − 0.730, P < 0.001). The AUC of the ROC curve was 0.900, the specificity and the sensitivity were 84.7% and 78.9%, respectively, which indicating that miR-211-5p had diagnostic value for AS. Survival analysis showed that patients with low miR-211-5p expression were more likely to have cardiovascular end-point events (Log rank P = 0.013). Conclusion Serum miR-211-5p could be used as a new biomarker for the diagnosis of AS, and the low expression of miR-211-5p is associated with the poor prognosis of AS.


2021 ◽  
Vol 7 (5) ◽  
pp. 3896-3904
Author(s):  
Daoting Deng ◽  
Hong Zhang ◽  
Junxi Liu ◽  
Lina Ma ◽  
Xinrui Lei ◽  
...  

To explore exosomal miR-375 expression in gastric cancer patients and its relationship with patient prognosis. A total of 53 patients diagnosed with gastric cancer in our hospital from May 2014 to May 2016 were included as the gastric cancer group, and 46 healthy women who came to our hospital for physical examination during the same period were enrolled as the healthy group. Exosomal miR-375 expression level was detected using qRT-PCR, and the diagnostic performance and prognostic significance of exosomal miR-375 in gastric cancer were explored. The gastric cancer group showed increased exosomal miR-375 expression than the healthy group (P< 0.05); Kaplan-Meier survival analysis exhibited that serum exosomal miR-375 has an AUC of 0.778, sensitivity of 69.57%, and specificity of 75.47%, whereas Cox regression analysis showed that the miR-375 expression in exosomes was an independent risk factor affecting the prognosis of gastric cancer patients (P< 0.05). Patient with gastric cancer showed upregulated miR-375 expression in serum exosomes. Serum exosomal miR-375 was found to has positive sensitivity and specificity in the diagnosis of gastric cancer, which may be associated with poor prognosis of gastric cancer patients.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jinfeng Zhu ◽  
Chen Luo ◽  
Jiefeng Zhao ◽  
Xiaojian Zhu ◽  
Kang Lin ◽  
...  

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p &lt; 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.


2021 ◽  
Author(s):  
Pegah Farrokhi ◽  
Alireza Sadeghi ◽  
Mehran sharifi ◽  
Payam Dadvand ◽  
Rachel Riechelmann ◽  
...  

AbstractAimThis study aimed to evaluate and compare the efficacy and toxicity of common regimens used as perioperative chemotherapy including ECF, DCF, FOLFOX, and FLOT to identify the most effective chemotherapy regimen with less toxicity.Material and MethodsThis retrospective cohort study was based on 152 eligible gastric cancer patients recruited in a tertiary oncology hospital in Isfahan, Iran (2014-2019). All resectable gastric cancer patients who had received one of the four chemotherapy regimens including ECF, DCF, FOLFOX, or FLOT, and followed for at least one year (up to five years) were included. The primary endpoint of this study was Overall Survival (OS), Progression-Free Survival (PFS), Overall Response Rate (ORR), and R0 resection. We also considered toxicity according to CTCAE (v.4.0) criteria as a secondary endpoint. Cox -regression models were used applied to estimate OS and PFS time, controlled for relevant covariates.ResultsOf included patients, 32(21%), 51(33.7%), 37(24.3%), and 32(21%) had received ECF, DCF, FOLFOX and FLOT, respectively. After the median 25 months follow-up, overall survival was higher with the FLOT regimen in comparison with other regimens (hazard ratio [HR] = 0. 052). The median OS of the FLOT regimen was not reachable in Kaplan-Meier analysis and the median OS was 28, 26, and 23 months for DCF, FOLOFX, and ECF regimens, respectively. On the other hand, a median PFS of 25, 17, 15, and 14 months was observed for FLOT, DCF, FOLFOX, and ECF regimens, respectively (Log-rank = 0. 021). FLOT regimen showed 84. 4% ORR which was notably higher than other groups (p-value<0. 01).ConclusionsFor resectable gastric cancer patients, the perioperative FLOT regimen seemed to lead to a significant improvement in patients’ OS and PFS in comparison with ECF, DCF, and FOLFOX regimens. As such, the FLOT regimen could be considered as the optimal option for managing resectable gastric cancer patients.


2021 ◽  
Author(s):  
Zongxian Zhao ◽  
Shuliang Li ◽  
Shilong Li ◽  
Jun Wang ◽  
Hai Lin ◽  
...  

Abstract BackgroundGastric cancer (GC) is one of the most common and fatal cancers worldwide and effective biomarkers aids in GC management and prognosis. Hence, we explored the role and function of cadherin 6 (CDH6) in diagnosis and prognosis of gastric cancer. MethodsThe expression level of CDH6 in GC tissue and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas dataset (TCGA). The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and expression of CDH6 were evaluated statistically and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. Forty-four GC tissues, corresponding adjacent normal tissues (n=20), and detailed clinical information were collected from Tianjin Medical University General Hospital, CDH6 expression level was detected for further validation. ResultsCDH6 was upregulated in GC samples compared with normal gastric tissue, and GSEA identified the citrate cycle tricarboxylic (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism oxidative phosphorylation, and pentose phosphate pathway as differentially enriched in GCs. According to the area under the ROC curve (AUC) (AUC=0.829 in TCGA and 0.966 in GSE54129), CDH6 had high diagnostic efficiency. Patients with high expression of CDH6 was associated with higher T classification and worse prognoses than those with low CDH6 expression in GC. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). ConclusionCDH6 was upregulated in GC and high CDH6 expression indicated higher T classification and worse prognoses. CDH6 could be a potentially independent molecular biomarker for diagnosis and prognosis of GC.


2020 ◽  
Vol 10 ◽  
Author(s):  
Xin Yin ◽  
Tianyi Fang ◽  
Yimin Wang ◽  
Chunfeng Li ◽  
Yufei Wang ◽  
...  

BackgroundSurgery combined with postoperative chemotherapy is an effective method for treating patients with gastric cancer (GC) in Asia. The important roles of systemic inflammatory response in chemotherapy have been gradually verified. The purpose of this study was to assess the difference in clinical effectiveness of FOLFOX (oxaliplatin + leucovorin + 5-fluorouracil) and XELOX (oxaliplatin + capecitabine), and the prognostic value of postoperative platelet–lymphocyte ratio (PLR) in the XELOX group.MethodsPatients who received radical gastrectomy combined with postoperative chemotherapy between 2004 and 2014 were consecutively selected into the FOLFOX and XELOX groups. Group bias was reduced through propensity score matching, which resulted in 278 patients in each group. Cut-off values of systemic immune inflammation (SII) score and PLR were obtained by receiver operating characteristic curve. Kaplan–Meier and Log-rank tests were used to analyze overall survival. The chi-square test was used to analyze the association between clinical characteristics and inflammatory indexes. Univariate and multivariate analyses based on Cox regression analysis showed independent risk factors for prognosis. The nomogram was made by R studio.ResultsPatients receiving XELOX postoperative chemotherapy had better survival than those receiving FOLFOX (P &lt; 0.001), especially for stage III GC (P = 0.002). Preoperative SII was an independent risk factor for prognosis in the FOLFOX group, and PLR of the second postoperative chemotherapy regimen in the XELOX group, combined with tumor size and pTNM stage, could construct a nomogram for evaluating recurrence and prognosis.ConclusionXELOX is better than FOLFOX for treatment of GC in Chinese patients, and a nomogram constructed by PLR, tumor size and pTNM stage can predict recurrence and prognosis.


2020 ◽  
Vol 162 (12) ◽  
pp. 3067-3080
Author(s):  
Yizhou Wan ◽  
Roushanak Rahmat ◽  
Stephen J. Price

Abstract Background Measurement of volumetric features is challenging in glioblastoma. We investigate whether volumetric features derived from preoperative MRI using a convolutional neural network–assisted segmentation is correlated with survival. Methods Preoperative MRI of 120 patients were scored using Visually Accessible Rembrandt Images (VASARI) features. We trained and tested a multilayer, multi-scale convolutional neural network on multimodal brain tumour segmentation challenge (BRATS) data, prior to testing on our dataset. The automated labels were manually edited to generate ground truth segmentations. Network performance for our data and BRATS data was compared. Multivariable Cox regression analysis corrected for multiple testing using the false discovery rate was performed to correlate clinical and imaging variables with overall survival. Results Median Dice coefficients in our sample were (1) whole tumour 0.94 (IQR, 0.82–0.98) compared to 0.91 (IQR, 0.83–0.94 p = 0.012), (2) FLAIR region 0.84 (IQR, 0.63–0.95) compared to 0.81 (IQR, 0.69–0.8 p = 0.170), (3) contrast-enhancing region 0.91 (IQR, 0.74–0.98) compared to 0.83 (IQR, 0.78–0.89 p = 0.003) and (4) necrosis region were 0.82 (IQR, 0.47–0.97) compared to 0.67 (IQR, 0.42–0.81 p = 0.005). Contrast-enhancing region/tumour core ratio (HR 4.73 [95% CI, 1.67–13.40], corrected p = 0.017) and necrotic core/tumour core ratio (HR 8.13 [95% CI, 2.06–32.12], corrected p = 0.011) were independently associated with overall survival. Conclusion Semi-automated segmentation of glioblastoma using a convolutional neural network trained on independent data is robust when applied to routine clinical data. The segmented volumes have prognostic significance.


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