scholarly journals High Expression of COL17A1 Predicts Poor Prognosis and Promotes the Tumor Progression via NF-κB Pathway in Pancreatic Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Feiyu Mao ◽  
Duguang Li ◽  
Zechang Xin ◽  
Yan Du ◽  
Xiaodong Wang ◽  
...  

COL17A1 (collagen type XVII alpha 1 chain) is known to be upregulated and has a prognostic role in many malignancies, as well as contributing to cell proliferation, apoptosis, and invasion. However, little knowledge is available on the expression and prognostic value of COL17A1 in pancreatic adenocarcinoma (PDAC). In our study, we searched the public database and found that mRNA and protein levels of COL17A1 are commonly upregulated in PDAC tissues. The immunohistochemical analysis conducted by us revealed enhanced expression of COL17A1 protein in 169 PDAC samples compared with that in 67 adjacent normal tissues. We also observed a significantly positive correlation between COL17A1 expression and lymph node metastasis ( p < 0.0001 ), TNM clinical stage ( p < 0.0001 ), and pathology differentiation ( p < 0.01 ). The KM-plot results indicated that PDAC patients with a high COL17A1 expression have a poorer overall survival ( p < 0.001 ) than those with a low COL17A1 expression. The result of the Cox regression analysis of multivariate data suggested COL17A1 is an independent prognostic indicator of PDAC patients’ overall survival. CCK-8, wound healing, and transwell assays suggested that COL17A1 knockdown markedly inhibited tumor proliferation and invasion in PDAC cells, and cells with COL17A1 overexpression had a prominently higher proliferative and invasive capacity. Knockdown of COL17A1 significantly upregulated the apoptosis rate. We deduce that upregulated COL17A1 activated the NF-κB pathway in PDAC cells. In summary, our studies showed the prognostic value of COL17A1 in PDAC and that COL17A1 may act as a molecular therapeutic target for PDAC treatment.

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Xiumei Wang ◽  
Yongqiang Liu ◽  
Qiong Qin ◽  
Ti Zheng

Abstract Aim: To explore the prognostic value of clusterin (CLU) in hepatocellular carcinoma (HCC) patients treated with oxaliplatin (OXA). Methods: Relative expression of plasma CLU mRNA was examined via fluorescence quantitative real-time PCR (qRT-PCR), and CLU protein level in tissue samples was detected through immunohistochemistry. Chi-square test was used to analyze the relationship between CLU mRNA expression and clinical features of HCC patients treated with OXA. Kaplan–Meier method was performed to assess overall survival for the patients, and prognostic value of CLU in HCC patients was estimated via Cox regression analysis. Results: CLU expression in plasma and tissue specimens was significantly higher among HCC patients than in non-malignant controls (P &lt; 0.001 for both). Moreover, elevated CLU mRNA was closely related to tumor stage, lymph node metastasis and response to OXA (P &lt; 0.05). HCC patients with high CLU expression showed poor response to OXA. In addition, low CLU levels predicted long overall survival time among the study subjects (20.8 vs. 36.6 months, P &lt; 0.001). CLU was an independent prognostic indicator for HCC patients treated with OXA (HR = 2.587, 95%CI = 1.749–3.828, P &lt; 0.001). Conclusion: CLU may be a novel prognostic marker for HCC patients treated with OXA.


2020 ◽  
Author(s):  
Shuangqing Cao ◽  
Lei Zheng

Abstract Background: MicroRNA-195 (miR-195), a tumor suppressor, had reported to be involved in carcinogenesis and the progression of some cancers. However, the prognostic value of miR-195 in cervical cancer remained unclear. The purpose of this study was to detect the expression of miR-195 in cervical cancer tissues and to investigate its correlation with tumor progression and prognosis.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of miR-195 in cervical cancer tissues and corresponding adjacent normal tissues. The relationship between miR-195 expression and clinical characteristics of patients was analyzed by chi-square test. Kaplan-Meier method was applied to compare the overall survival, and the prognostic value of miR-195 was estimated via cox regression analysis.Results: Compared with normal tissues, miR-195 expression was significantly down-regulated in cervical cancer tissues (P < 0.001). Importantly, decreased expression of miR-195 was closely associated with FIGO stage, lymph node metastasis and vascular invasion (P < 0.05). Additionally, Kaplan-Meier analysis indicated that patients with high miR-195 expression had obviously longer overall survival than those with low miR-195 expression (log rank test, P = 0.001). And miR-195 was an independent prognostic factor of cervical cancer patients via univariate and multivariate cox regression analyses.Conclusions: Decreased expression of miR-195 is associated with the progression of cervical cancer. And miR-195 may have potency to predict the prognosis of cervical cancer.


2020 ◽  
Author(s):  
Yue Zhao ◽  
Xiangjun Kong ◽  
Hongbing Wang

Abstract Background: Lung cancer is one of the most common cancers, with high morbidity and mortality. MiRNAs are proved to play important roles in various human cancers. In our study, we aimed to explore the prognostic value of miR-181 in lung cancerMethods: Quantitative real-time polymerase chain reaction (QRT-PCR) was used to detect the expression level of miR-181 in lung cancer tissues and the paired non-cancerous tissues. The relationship between miR-181 expression and clinicopathologic parameters were analyzed by chi-square test. Kaplan-Meier method with log rank test was applied for overall survival analysis. Furthermore, the Cox regression analyses were performed to evaluate the prognostic value of miR-181 in lung cancer.Results: Down-regulated miR-181 expression was observed in lung cancer tissues (P<0.001), moreover, its expression was significantly correlated with TNM stage (P=0.015) and metastasis (P=0.000). In addition, lung cancer patients with lower miR-181 expression level had poorer overall survival than those with higher expression (log rank test, P=0.011). Cox regression analysis suggested that miR-181 was an independent prognostic factor for lung cancer (HR=1.961, 95%CI=1.135-3.388, P=0.016).Conclusion: MiR-181 may be a tumor suppressor gene in lung cancer, which can predict outcomes for the patients.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Xin Shi ◽  
Xingfa Guan

Abstract Background Osteosarcoma (OS) is a malignancy predominantly occurred in children and adolescents. Numerous microRNAs are involved in the pathogenesis of various cancers. This study aimed to investigate the expression profiles of miR-99b and its prognostic value in OS patients, and further analyze the biological function of miR-99b in the tumor progression by using OS cells. Methods Expression of miR-99b was measured using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were performed to evaluate the prognostic value of miR-99b. OS cell lines were used to investigate the effects of miR-99b on cell proliferation, migration and invasion. Results A significant decreased expression of miR-99b was observed in the OS tissues and cell lines respectively compared with the normal tissues and cells. Aberrant expression of miR-99b was associated with the patients’ metastasis and TNM stage, and could be used to predict the prognosis of OS. The expression of miR-99b was regulated in vitro by cell transfection, and we found that the overexpression of miR-99b led to suppressed cell proliferation, migration and invasion, whereas the knockdown of miR-99b resulted in the opposite results. Conclusions In one word, the aberrantly expressed miR-99b serves a prognostic biomarker for OS patients. OS cell proliferation, migration and invasion can be inhibited by the overexpression of miR-99b, suggesting that the methods to increase miR-99b expression may be novel therapeutic strategies in OS.


2017 ◽  
Vol 32 (4) ◽  
pp. 409-414 ◽  
Author(s):  
Guo-Dong Gao ◽  
Bo Sun ◽  
Xian-Bin Wang ◽  
Shi-Meng Wang

Background This study aimed to evaluate the correlation between neutrophil to lymphocyte ratio (NLR) with overall survival (OS) of esophageal squamous cell carcinoma (ESCC) patients. Method Records of patients with diagnosed ESCC were reviewed. Leukocyte counts and patients' characteristics were extracted from their clinical records to calculate NLR. Correlation between NLR and baseline characteristics with overall survival (OS) was then analyzed using Cox regression. The patients were then separated into higher and lower NLR groups according to median NLR. OS was further compared between the 2 groups. Results A total of 1281 patients were included in the study. Cox regression analysis showed a significant correlation of NLR with OS of ESCC patients. The median pretreatment NLR was identified as 2.86. Higher NLR was associated with worse prognosis in terms of OS. Conclusions Pretreatment NLR is independently associated with OS of ESCC patients. Therefore, NLR may be used as a predictive indicator for pretreatment evaluation and adjustment of treatment regimen.


2021 ◽  
Vol 8 ◽  
Author(s):  
Wenting Liu ◽  
Kaiting Jiang ◽  
Jingya Wang ◽  
Ting Mei ◽  
Min Zhao ◽  
...  

BackgroundGlucosamine 6-phosphate N-acetyltransferase (GNPNAT1) is a key enzyme in the hexosamine biosynthetic pathway (HBP), which functions as promoting proliferation in some tumors, yet its potential biological function and mechanism in lung adenocarcinoma (LUAD) have not been explored.MethodsThe mRNA differential expression of GNPNAT1 in LUAD and normal tissues was analyzed using the Cancer Genome Atlas (TCGA) database and validated by real-time PCR. The clinical value of GNPNAT1 in LUAD was investigated based on the data from the TCGA database. Then, immunohistochemistry (IHC) of GNPNAT1 was applied to verify the expression and clinical significance in LUAD from the protein level. The relationship between GNPNAT1 and epigenetics was explored using the cBioPortal database, and the miRNAs regulating GNPNAT1 were found using the miRNA database. The association between GNPNAT1 expression and tumor-infiltrating immune cells in LUAD was observed through the Tumor IMmune Estimation Resource (TIMER). Finally, Gene set enrichment analysis (GSEA) was used to explore the biological signaling pathways involved in GNPNAT1 in LUAD.ResultsGNPNAT1 was upregulated in LUAD compared with normal tissues, which was verified through qRT-PCR in different cell lines (P &lt; 0.05), and associated with patients’ clinical stage, tumor size, and lymphatic metastasis status (all P &lt; 0.01). Kaplan–Meier (KM) analysis suggested that patients with upregulated GNPNAT1 had a relatively poor prognosis (P &lt; 0.0001). Furthermore, multivariate Cox regression analysis indicated that GNPNAT1 was an independent prognostic factor for LUAD (OS, TCGA dataset: HR = 1.028, 95% CI: 1.013–1.044, P &lt; 0.001; OS, validation set: HR = 1.313, 95% CI: 1.130–1.526, P &lt; 0.001). GNPNAT1 overexpression was correlated with DNA copy amplification (P &lt; 0.0001), low DNA methylation (R = −0.52, P &lt; 0.0001), and downregulation of hsa-miR-30d-3p (R = −0.17, P &lt; 0.001). GNPNAT1 expression was linked to B cells (R = −0.304, P &lt; 0.0001), CD4+T cells (R = −0.218, P &lt; 0.0001), and dendritic cells (R = −0.137, P = 0.002). Eventually, GSEA showed that the signaling pathways of the cell cycle, ubiquitin-mediated proteolysis, mismatch repair and p53 were enriched in the GNPNAT1 overexpression group.ConclusionGNPNAT1 may be a potential prognostic biomarker and novel target for intervention in LUAD.


2020 ◽  
Author(s):  
Xianfeng Zhang ◽  
Xianjun Zhang ◽  
Xinguo Li ◽  
Hongbing Bao ◽  
Guang Li ◽  
...  

Abstract Background: Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) was over-expressed in some tumors, including hepatocellular carcinoma (HCC). However, the clinical significance of NUCKS1 in HCC was still unclear. The aim of this study was to explore the expression and prognostic value of NUCKS1 in HCC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative mRNA expression of NUCKS1 in HCC tissues and corresponding adjacent normal tissues. The relationship between NUCKS1 expression and clinical characteristics of patients was analyzed by c2 test. Kaplan-Meier method and cox regression analysis were applied to estimate the prognostic value of NUCKS1 in HCC. Results: Compared with normal tissues, the relative mRNA expression level of NUCKS1 was significantly up-regulated in HCC tissues (P < 0.001). And high NUCKS1 expression was closely associated with tumor differentiation, TNM stage, vascular invasion and metastasis (P < 0.05). Kaplan-Meier analysis revealed that the overall survival of HCC patients with low expression of NUCKS1 was obviously longer than those with high NUCKS1 expression (log rank test, P = 0.001). NUCKS1 was an independent prognostic factor of HCC patients via univariate and multivariate cox regression analyses.Conclusions: NUCKS1 may be correlated with the progression of HCC and may serve as a potential factor for the prognosis of this disease.


2020 ◽  
Author(s):  
Jun Ji ◽  
Jiahui Chen ◽  
Anqiang Wang ◽  
Wei Zhang ◽  
Hongge Ju ◽  
...  

Abstract Background: To detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyze the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods: A total of 94 patients with GC who underwent surgical resection were enrolled in this study. The expression of KK-LC-1 in GC tissues was detected by immunohistochemistry. The assessment of KK-LC-1 expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of KK-LC-1 in the cytoplasm and was scored to achieve respective H-score values. The correlations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. Results: In the cytoplasm, the expression of KK-LC-1 in tumor tissues was significantly higher than that in normal tissues (P < 0.001, respectively). Using the median H-score as the cutoff value, it was discovered that, GC patients with higher levels of KK-LC-1expression in the cytoplasm, had favorable overall survival (P =0.016), and it was still statistically meaningful in Cox regression analysis. At the same time, the study found that there was a negative correlation between KK-LC-1’s protein expression and the pathological grade of the tumor (P = 0.036). Conclusions: Our research data shows that KK-LC-1’s expression in GC is higher than that of normal tissues, which is associated with a longer overall survival in GC. KK-LC-1 can be used as a biomarker for GC patients with good prognosis.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16521-e16521
Author(s):  
Orazio Caffo ◽  
Emilio Bria ◽  
Ugo De Giorgi ◽  
Marcello Tucci ◽  
Elisa Biasco ◽  
...  

e16521 Background: High NLR has been reported to be a poor prognostic indicator in both first and second mCRPC lines, while no information is available concerning this issue in pts treated in third line therapy. The present study is aimed to assess the possible relationship between third line clinical outcomes and NLR in a series of mCRPC pts treated with a NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] after the failure of docetaxel (DOC) and another NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. Cox regression analysis was used to assess the independent prognostic value of a series of pretreatment covariates, in terms of overall survival (OS), comprising NLR. Results: A consecutive series of 476 mCRPC pts with bone (86%), nodal (56%) or visceral (15%) mets, was collected. All pts received a NA-based third line: 135 received AA, 221 CABA and 120 ENZ. Data on NLR were available for 398 pts (84%). In the univariate analyses, the NLR as a discrete variable dichotomized according to the Maximally Selected Log-Rank statistics (optimal cut-off: 3.66), was significantly associated with both OS and progression free survival (PFS), calculated from the third line start (p < 0.0001). At the multivariate analysis, NLR, performance status, pain, hemoglobin, alkaline phosphatase, treatment with AA and with CABA were independent prognostic factors for PFS, while NLR, performance status, hemoglobin, PSA, and lactate dehydrogenase were independent prognostic factors for OS. In Kaplan-Meier analysis, the median OS from the start of third-line was higher (14.2 vs 9.3 mos) in pts with NLR ≤ 3.1 compared to those with NLR > 3.1 (log-rank; P < 0.0001). Similarly, the median PFS was 5.5 and 3.8 (log-rank; P < 0.0001) in pts with NLR ≤ 3.66 and > 3.66, respectively. Conclusions: Our results, observed in the largest cohort of mCRCP pts treated with NA-based third line after DOC and another NA, confirms that NLR is an independent factor for PFS and OS also in this population.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 230-230
Author(s):  
Orazio Caffo ◽  
Emilio Bria ◽  
Ugo De Giorgi ◽  
Marcello Tucci ◽  
Luca Galli ◽  
...  

230 Background: High NLR has been reported to be a poor prognostic indicator in both first and second mCRPC lines, while no information is available concerning this issue in pts treated in third line therapy. The present study is aimed to assess the possible relationship between third line clinical outcomes and NLR in a series of mCRPC pts treated with a NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] after the failure of docetaxel (DOC) and another NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. Cox regression analysis was used to assess the independent prognostic value of a series of pretreatment covariates, in terms of overall survival (OS), comprising NLR. Results: A consecutive series of 476 mCRPC pts with bone (86%), nodal (56%) or visceral (15%) mets, was collected. All pts received a NA-based third line: 135 received AA, 221 CABA and 120 ENZ. Data on NLR were available for 398 pts (84%). In the univariate analyses, the NLR as a discrete variable dichotomized according to the Maximally Selected Log-Rank statistics (optimal cut-off: 3.66), was significantly associated with both OS and progression free survival (PFS), calculated from the third line start (p < 0.0001). At the multivariate analysis, NLR, performance status, pain, hemoglobin, alkaline phosphatase, treatment with AA and with CABA were independent prognostic factors for PFS, while NLR, performance status, hemoglobin, PSA, and lactate dehydrogenase were independent prognostic factors for OS . In Kaplan-Meier analysis, the median OS from the start of third-line was higher (14.2 vs 9.3 mos) in pts with NLR ≤ 3.1 compared to those with NLR > 3.1 (log-rank; P < 0.0001). Similarly, the median PFS was 5.5 and 3.8 (log-rank; P < 0.0001) in pts with NLR ≤ 3.66 and > 3.66, respectively. Conclusions: Our results, observed in the largest cohort of mCRCP pts treated with NA-based third line after DOC and another NA, confirms that NLR is an independent factor for PFS and OS also in this population.


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