<i><scp>CGB</scp>5</i> expression is independently associated with poor overall survival and recurrence‐free survival in patients with advanced gastric cancer

Yang, Yuxin; Shi, Yonghong; Hou, Yan; Lu, Ying; Yang, Jinliang

doi:10.1002/cam4.1364

Cited by 17 publications

(10 citation statements)

References 31 publications

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“…It has been considered as an independent prognostic factor for GC, which is consistent with our results[ 25 ]. Furthermore, CGB5 is correlated with a poor prognosis in patients with advanced GC[ 26 , 27 ]. It has been reported that LGR6 might be involved in the development of GC via the PI3K/AKT/mTOR axis[ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer

Qiu¹,

Song²,

Liu³

et al. 2020

WJGO

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BACKGROUND Gastric cancer (GC) is the most commonly diagnosed malignancy worldwide. Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC. AIM To construct an immune-related gene (IRG) signature for accurately predicting the prognosis of patients with GC. METHODS Differentially expressed genes (DEGs) between 375 gastric cancer tissues and 32 normal adjacent tissues were obtained from The Cancer Genome Atlas (TCGA) GDC data portal. Then, differentially expressed IRGs from the ImmPort database were identified for GC. Cox univariate survival analysis was used to screen survival-related IRGs. Differentially expressed survival-related IRGs were considered as hub IRGs. Genetic mutations of hub IRGs were analyzed. Then, hub IRGs were selected to conduct a prognostic signature. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prognostic performance of the signature. The correlation of the signature with clinical features and tumor-infiltrating immune cells was analyzed. RESULTS Among all DEGs, 70 hub IRGs were obtained for GC. The deletions and amplifications were the two most common types of genetic mutations of hub IRGs. A prognostic signature was identified, consisting of ten hub IRGs (including S100A12, DEFB126, KAL1, APOH, CGB5, GRP, GLP2R, LGR6, PTGER3 , and CTLA4 ). This prognostic signature could accurately distinguish patients into high- and low- risk groups, and overall survival analysis showed that high risk patients had shortened survival time than low risk patients ( P < 0.0001). The area under curve of the ROC of the signature was 0.761, suggesting that the prognostic signature had a high sensitivity and accuracy. Multivariate regression analysis demonstrated that the prognostic signature could become an independent prognostic predictor for GC after adjustment for other clinical features. Furthermore, we found that the prognostic signature was significantly correlated with macrophage infiltration. CONCLUSION Our study proposed an immune-related prognostic signature for GC, which could help develop treatment strategies for patients with GC in the future.

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Section: Discussionmentioning

confidence: 99%

Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer

Qiu¹,

Song²,

Liu³

et al. 2020

WJGO

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“…β-hCG is well-known as an sensitive biomarker for trophoblastic tumors and diseases. Recently, studies have found that β-hCG was ectopically elevated in the histological and serological samples of renal cell carcinoma [14], hepatocellular carcinoma [15], gastric cancer [16] and colon cancer patients [17]. Moreover, β-hCG was regarded as a biomarker to surveille recurrence and follow-up of malignant germ cell and sex cord-stromal tumors as Class 2B evidence in the 2018 NCCN clinical practice guidelines in Ovarian Cancer [18].…”

Section: Discussionmentioning

confidence: 99%

β-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway

Wei

Gao

et al. 2018

Cell Cycle

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Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with typically extensive intraperitoneal implantation leading to poor prognosis. Our previous study preliminarily demonstrated β-hCG can promote tumorigenesis in immortalized nontumorigenic ovarian epithelial cells. In this study, the roles and mechanisms of β-hCG in regulating EOC proliferation and metastasis were thoroughly explored. First, histologically, β-hCG was aberrantly overexpressed in human EOC metastatic tissues, and significantly correlated with FIGO stage, tumor size, differentiation, histologic grade and high grade serous ovarian carcinoma (HGSOC) (P < 0.05). However, serologically, β-hCG expression showed no significant difference between EOC and nonmalignant ovarian patients. Second, β-hCG was confirmed to have no significant effects on EOC proliferation in vitro and in vivo, while β-hCG upregulation was proven to promote migration and invasion ability in ES-2 and OVCAR-3 cells in vitro (P < 0.05), and β-hCG downregulation in SKOV3 cells had the opposite effect. Moreover, more invadopodia protrusions, mitochondria accumulations and cytoskeletal rearrangements were observed in β-hCG-overexpressing ES-2 cells, while β-hCG-depleted SKOV3 cells produced the opposite effect. Furthermore, β-hCG was confirmed to clearly facilitate intraperitoneal metastasis in nude mouse orthotopic ovarian xenograft models. Importantly, these effects of β-hCG were mediated by activation of the ERK/MMP2 signaling pathway, independently of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) presence, and inhibition the pathway with the p-ERK1/2 inhibitor SCH772984 significantly impaired the tumor-promoting effects induced by β-hCG. Collectively, these data provide new insight into the roles and mechanisms of β-hCG in regulating EOC metastasis through ERK/MMP2 signaling pathway and may become a new target for therapeutic intervention.

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“…In addition, high expression of CCL21 was related to lymph node metastasis and poor prognosis in GC patients [ 27 ]. CGB5 was found to be overexpressed in most GC tissues and was considered as an independent predictor of OS and recurrence-free survival for GC patients [ 28 ]. As the specific ligand of HER4, the role of NRG4 in GC remains controversial.…”

Section: Discussionmentioning

confidence: 99%

A signature of seven immune‐related genes predicts overall survival in male gastric cancer patients

et al. 2021

Cancer Cell Int

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Background Gastric cancer (GC) has a high mortality rate and is one of the most fatal malignant tumours. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) associated with the prognosis of male GC. Methods RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from the Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT. Results A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified to be significantly associated with the overall survival (OS) of male GC patients. Survival analysis indicated that patients in the high-risk group exhibited a poor clinical outcome. The results of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and validated cohorts. Besides, the results of tumour-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumour immune microenvironment. Conclusions Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.

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CGB5 expression is independently associated with poor overall survival and recurrence‐free survival in patients with advanced gastric cancer

Cited by 17 publications

References 31 publications

Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer

Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer

β-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway

A signature of seven immune‐related genes predicts overall survival in male gastric cancer patients

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