Overexpression of cellular FLICE-inhibitory protein (FLIP) in gastric adenocarcinoma

2004 ◽  
Vol 106 (4) ◽  
pp. 397-405 ◽  
Author(s):  
Xiao-Dong ZHOU ◽  
Jie-Ping YU ◽  
Jin LIU ◽  
He-Sheng LUO ◽  
Hong-Xia CHEN ◽  
...  

The aim of the present study was to investigate the prevalence of c-FLIP [cellular FLICE-inhibitory protein, where FLICE is Fas-associated death domain (FADD)-like interleukin-1β-converting enzyme] expression in gastric adenocarcinoma and its possible implications for the progression of the cancer. Expression of c-FLIP in 48 gastric adenocarcinomas and their normal counterparts was analysed by reverse transcriptase PCR, Western blotting and immunohistochemistry. In situ cell apoptosis was detected by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay. As a result, c-FLIP transcripts were constitutively expressed in gastric adenocarcinomas and their levels were significantly higher than those in matched normal tissues (P<0.01). Immunohistochemically, the c-FLIP protein was also found to be expressed in all gastric adenocarcinomas (48/48), and 68.8% (33/48) showed an intense immunostaining; in contrast, only 75% (36/48) of normal gastric mucosa showed positive staining and none of them immunostained intensely. The abundance of c-FLIP protein was significantly higher in carcinoma than in normal gastric mucosa (6.93±0.58 versus 3.19±0.26, P<0.01) and showed a reverse correlation with apoptotic index in adenocarcinoma, but not in normal mucosa. In addition, abundance of c-FLIP was significantly associated with lymph node metastasis at both mRNA level (P<0.05) and protein level (P<0.01). Western-blot analysis showed that the expression levels of the long form of c-FLIP and the short form of c-FLIP in adenocarcinomas were 2.6-fold and 2.8-fold (P<0.01) higher than those in normal tissues respectively. However, no significant difference was found between the expression levels of the two isoforms in both adenocarcinomas or normal tissues. In conclusion, overexpression of c-FLIP is tumour specific, which may be one of the in vivo mechanisms by which tumour cells escape from apoptotic death during the malignant transformation, and plays an important role in lymph node metastasis of gastric adenocarcinoma, which ultimately contributes to the tumour progression.

2021 ◽  
Vol 11 (2) ◽  
pp. 126
Author(s):  
Noshad Peyravian ◽  
Stefania Nobili ◽  
Zahra Pezeshkian ◽  
Meysam Olfatifar ◽  
Afshin Moradi ◽  
...  

This study aimed at building a prognostic signature based on a candidate gene panel whose expression may be associated with lymph node metastasis (LNM), thus potentially able to predict colorectal cancer (CRC) progression and patient survival. The mRNA expression levels of 20 candidate genes were evaluated by RT-qPCR in cancer and normal mucosa formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients. Receiver operating characteristic curves were used to evaluate the prognosis performance of our model by calculating the area under the curve (AUC) values corresponding to stage and metastasis. A total of 100 FFPE primary tumor tissues from stage I–IV CRC patients were collected and analyzed. Among the 20 candidate genes we studied, only the expression levels of VANGL1 significantly varied between patients with and without LNMs (p = 0.02). Additionally, the AUC value of the 20-gene panel was found to have the highest predictive performance (i.e., AUC = 79.84%) for LNMs compared with that of two subpanels including 5 and 10 genes. According to our results, VANGL1 gene expression levels are able to estimate LNMs in different stages of CRC. After a proper validation in a wider case series, the evaluation of VANGL1 gene expression and that of the 20-gene panel signature could help in the future in the prediction of CRC progression.


2021 ◽  
pp. 1-7
Author(s):  
Lili Huang ◽  
Yan Zhou ◽  
Qiuwei Sun ◽  
Lei Cao ◽  
Xueguang Zhang

BACKGROUND and OBJECTIVE: Gastric adenocarcinoma (GAC) is one of the most common malignancies. Increasing data have indicated a correlation between soluble B7-H3 (sB7-H3) levels and tumor malignancies. In this study, we aim to investigate the level of soluble B7-H3 in serum of GAC patients. Further, we analyze the correlation between sB7-H3 level and tissue B7-H3 expression and explore the clinical evaluation value of sB7-H3 associated with pathological characteristics and prognosis of GAC patients. METHODS: One hundred and twenty-eight serum and tissue samples of GAC 20 serum and tissue samples of gastritis patients and 77 serum, 5 tissue samples of healthy controls were collected. The serum levels of sB7-H3 were detected by Enzyme-linked immunosorbent assay (ELISA), while the expression of membrane B7-H3 (mB7-H3) and Ki67 were evaluated by immunohistochemistry. The correlation between sB7-H3 and mB7-H3, sB7-H3 and Ki67, sB7-H3 or mB7-H3 and clinical features were analyzed by Pearson’s Chi-square test. RESULTS: Both serum level of sB7-H3 and tissue B7-H3 of GAC patients were significantly higher than those of gastritis patients and healthy controls. sB7-H3 level was correlated with total B7-H3 expression in tissues (r= 0.2801, P= 0.0014). Notably, the concentration of sB7-H3 was correlated with its expression of membrane form in tumor cells (r= 0.3251, P= 0.002) while not in stromal cells (r= 0.07676, P= 0.3891). Moreover, the levels of sB7-H3 in patients with TNM stage III/IV or with Infiltration depth T3/T4 or with lymph node metastasis were significantly higher than those of patients with TNM stage I/II (P= 0.0020) or with Infiltration depth T1/T2 (P= 0.0169) or with no lymph node metastasis (P= 0.0086). Tumor B7-H3 score, but not stromal B7-H3 score, in patients with TNM stage III/IV or with lymph node metastasis was significantly higher than those with TNM stage I/II (P= 0.0150) or with no lymph node metastasis (P= 0.182). CONCLUSIONS: Soluble B7-H3 level may reflect the tissue B7-H3 expression on tumor cells of GAC tissues. Elevated level of sB7-H3 in serum suggests poor clinical pathological characteristics of GAC patients.


Surgery Today ◽  
2011 ◽  
Vol 41 (5) ◽  
pp. 688-692 ◽  
Author(s):  
Seong-Gon Kim ◽  
Hye-Rim Park ◽  
Soo-Kee Min ◽  
Je-Yong Choi ◽  
Sung-Hoon Koh ◽  
...  

1994 ◽  
Vol 44 (12) ◽  
pp. 844-849 ◽  
Author(s):  
Shi-Nong Wang ◽  
Motohiro Miyauchi ◽  
Nobuko Koshikawa ◽  
Koshi Maruyama ◽  
Tetsuo Kubota ◽  
...  

Oncotarget ◽  
2016 ◽  
Vol 7 (41) ◽  
pp. 67212-67222 ◽  
Author(s):  
Junjie Bao ◽  
Abiyasi Nanding ◽  
Haibin Song ◽  
Rui Xu ◽  
Guofan Qu ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16554-e16554
Author(s):  
Yicheng Zhou ◽  
Honglei Zhu ◽  
Xuezhou Pang ◽  
Yang Shen ◽  
Yu He ◽  
...  

e16554 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide and has a very high morbidity and mortality rate. The IL-6/STAT3 axis can simultaneously promote the expansion of immunosuppressive cells.This study detected IL-6, STAT3 and PD-L1 in ESCC and analyzed the potential clinical application value. Methods: Between July 2018 and April 2019, 70 ESCC patients underwent radical thoracic surgery at Affiliated Hospital of North Sichuan Medical College. RT-PCR was used to detect PD-L1, IL-6, and STAT3 mRNA expression in cancer and adjacent normal tissues. Western blot detection of PD-L1, IL-6, and STAT3 was performed in 40 cancer and adjacent normal tissues. The correlation of PD-L1, IL-6 and STAT3 protein expression with tumor invasion depth, tumor size, lymph node metastasis,clinical stage and other clinicopathological characteristics as well as the correlation between the three proteins were analyzed statistically. Results: The mRNA levels of PD-L1, IL-6, and STAT3 in 70 ESCC patients were significantly different between cancerous and adjacent normal tissues (P < 0.001). In 40 ESCC patients, 28 ESCC tissues showed significantly higher PD-L1 expression than adjacent normal tissue (28/12, P < 0.001), 29 ESCC tissues showed significantly higher STAT3 expression (29/11,P = 0.009 ), and 27 ESCC tissues showed significantly higher IL-6 expression (27/13,P = 0.042). There was no correlation between PD-L1 expression and age, sex, tumor site or maximum tumor diameter, but PD-L1 expression showed a positive correlation with T stage (P = 0.009), lymph node metastasis (P = 0.044), and clinical stage (P = 0.033). There was no correlation between STAT3 expression and age, sex, tumor site, maximum tumor diameter, lymph node metastasis or clinical stage, but STAT3 expression showed a positive correlation with T stage (P = 0.025). IL-6 expression was not correlated with age, sex, maximum tumor diameter, lymph node metastasis or clinical stage, but IL-6 expression showed a positive correlation with T stage ( P = 0.003)and tumor site (P = 0.011). In addition, PD-L1 expression showed a positive correlation with STAT3 (P = 0.013) and IL-6 ( P = 0.008), and STAT3 showed a positive correlation with IL-6 ( P = 0.027). Conclusions: PD-L1, IL-6, and STAT3 are highly expressed in ESCC and their protein levels exhibit a positive correlation. The IL-6/STAT3 signaling pathway proteins may be a potential biomarker predicting the efficacy of immunotherapy by affecting the expression of PD-L1.


2004 ◽  
Vol 12 (6) ◽  
pp. 1273 ◽  
Author(s):  
Li-Jiang Liu ◽  
Xi-Ji Shu ◽  
Hong-Yan Zhen ◽  
Xiao-Dong Qiu ◽  
Hao Deng ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Lei Zhao ◽  
Yaming Cao

The expression of PD-L1 could be a novel biomarker which predicts that patients are more likely to respond to immunotherapy. Our study investigated the relationship among clinicopathological characteristics, prognosis, PD-L1 expression levels, and FOXP3+ Treg infiltration. In addition, the relationship among clinicopathological characteristics, prognosis, PD-L1 expression levels, and FOXP3+ Treg infiltration was explored. Furthermore, the relationship between PD-L1 expression and FOXP3+ Treg infiltration was examined. We found that 41.3% of pancreatic cancer patients had PD-L1-positive staining; both PD-L1 expression levels and FOXP3+ Treg infiltration were significantly associated with depth of invasion, lymph node metastasis, distant metastasis, and pTNM. In addition, PD-L1 expression and FOXP3+ Treg infiltration also could be prognostic biomarkers for pancreatic cancer.


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