scholarly journals Pontin Acts as a Potential Biomarker for Poor Clinical Outcome and Promotes Tumor Invasion in Hilar Cholangiocarcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Qi Sun ◽  
Fanni Li ◽  
Songyang Yu ◽  
Xiang Zhang ◽  
Feiyu Shi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hilar Cholangiocarcinoma ◽  
Multivariate Analyses ◽  
Malignant Tumors ◽  
Protein Levels ◽  
Node Metastasis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Cholangiocarcinoma Cell

Hilar cholangiocarcinoma (HC) is a devastating malignancy that carries a poor overall prognosis. As a member of the AAA+ superfamily, Pontin becomes highly expressed in several malignant tumors, which contributes to tumor progression and influences tumor prognosis. In our research, Pontin expression in tumor specimens resected from 86 HC patients was detected by immunohistochemistry. Interestingly, high expression of Pontin was significantly associated with lymph node metastasis (p=0.011) and tumor node metastasis (TNM) stage (p=0.005). The Kaplan–Meier overall survival rate and multivariate analyses were performed to evaluate the prognosis of patients with HC. Patients with high Pontin expression had significantly poorer overall survival outcomes. Multivariate analyses found that Pontin was an independent prognostic factor (p=0.001). Moreover, bioinformatics analysis confirmed the increase in Pontin mRNA expression levels in cholangiocarcinoma tissues. In addition, in vitro experiments showed that Pontin expression was inhibited at the mRNA as well as protein levels after transfection with Pontin siRNA in human cholangiocarcinoma cell lines. Moreover, significant suppression of cell invasion was observed after the downregulation of Pontin. Taken together, the present study suggested that Pontin could act as a potential prognostic predictor, which might be a new valuable molecular candidate for the prevention and treatment of HC.

scholarly journals TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chengwu Xiao ◽  
Wei Zhang ◽  
Meimian Hua ◽  
Huan Chen ◽  
Bin Yang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Prognostic Indicator ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

scholarly journals Pretreatment plasma d-dimer levels as an independent prognostic factor for overall survival among patients with advanced non-small-cell lung cancer

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096266
Author(s):  
Qianfei Liu ◽  
Jianbo He ◽  
Ruiling Ning ◽  
Liping Tan ◽  
Aiping Zeng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Small Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Multivariate Analyses ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kaplan Meier ◽  
D Dimer

Objective To evaluate the prognostic accuracy of d-dimer levels for advanced non-small-cell lung cancer (NSCLC). Methods This retrospective cohort study included 651 patients initially diagnosed with advanced NSCLC. Patients with d-dimer levels ≥0.5 mg/L were included in the high d-dimer group, whereas patients with lower levels were included in the normal group. Cumulative survival was estimated using Kaplan–Meier curves and compared using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. Results The median plasma d-dimer level in the study cohort was 0.61 ± 0.49 mg/L. d-dimer levels were elevated in 60.98% of patients, and 80.1% of such patients had adenocarcinoma. Univariate and multivariate analyses identified d-dimer content as an independent factor for the prognosis of NSCLC (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.19–1.98). Kaplan–Meier analysis revealed that high plasma d-dimer levels were associated with shorter overall survival (HR = 1.48, 95% CI = 1.19–1.84). In addition, the receipt of <2 lines of treatment was associated with a higher risk of death than the receipt of >2 lines. Conclusion The present results imply that pretreatment plasma d-dimer levels could represent a prognostic factor for advanced NSCLC.

scholarly journals TILs and Anti-PD1 Therapy: An Alternative Combination Therapy for PDL1 Negative Metastatic Cervical Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Huanhuan Yin ◽  
Wei Guo ◽  
Xiangling Sun ◽  
Ruili Li ◽  
Cuihua Feng ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Survival Time ◽  
Response Rate ◽  
Multivariate Analyses ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier

Background. We investigated the efficacy of TILs and anti-PD1 combination therapy in patients with metastatic cervical cancer with low MSI expression and PDL1-negative. Methods. A total of 80 patients were put on TILs and anti-PD1 combination therapy, and the progression-free survival time (PFS) and overall survival time (OS) were assessed by Kaplan–Meier analysis. Univariate and multivariate analyses were performed to identify factors that could predict the prognosis of metastatic cervical cancer in the previously described patients. Results. The objective response rate was 25%, whereas the mPFS and mOS were 6.1 and 11.3 months, respectively. The therapeutic efficacy was influenced by the characteristics of TILs, infection with HPV, and development of fever just after the therapy. Conclusion. Overall, our results show that the combination therapy of TILs and anti-PD1 significantly improves the prognosis of metastatic cervical cancer.

scholarly journals Objective quantitation of EGFR protein levels using Quantitative Dot Blot (QDB) method for prognosis of gastric cancer patients

2021 ◽  
Author(s):  
Lei Xin ◽  
Fangrong Tang ◽  
Bo Song ◽  
Maozhou Yang ◽  
Jiandi Zhang
Keyword(s):  
Gastric Cancer ◽  
Lung Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Cox Regression ◽  
Dot Blot ◽  
Protein Levels ◽  
Kaplan Meier ◽  
Gastric Cancer Patients

Background: One causing factor underlying failures of several clinical trials of anti-EGFR therapies is the lack of effective method to select patients overexpressing EGFR protein. Quantitative Dot Blot method (QDB) is proposed here to measure EGFR protein levels objectively and quantitatively. Its feasibility was evaluated for prognosis of overall survival (OS) of gastric cancer patients. Methods: FFPE slices of 2X5 microM from gastric and Lung cancer specimens were used to extract total tissue lysates for QDB measurement. Absolutely quantitated EGFR protein levels were used for Kaplan-Meier Overall Survival (OS) analysis of gastric cancer patients. Results: EGFR protein levels ranged from 0 to 772 pmole/g for gastric cancer specimens (n=246), and from 0 to 2695 pmole/g for lung cancer patients (n=81). Poor correlation was observed between quantitated EGFR levels and IHC scores with r=0.018, p=0.786 from Spearman correlation analysis. EGFR was identified as an independent negative prognostic biomarker for gastric patients only through absolute quantitation, with HR at 2.29 (95%CI:1.23-4.26, p=0.0089) from multivariate cox regression OS analysis. A cutoff of 207.7 pmole/g was proposed to stratify gastric cancer patients, with 5-year survival probability at 37% for those whose EGFR levels were above the cutoff, and at 64% those below the cutoff based on Kaplan-Meier OS analysis. p=0.0057 from Log Rank test. Conclusion: A QDB-based assay was developed for both gastric and Lung cancer specimens to measure EGFR protein levels absolutely, quantitatively and objectively. This assay should facilitate clinical trials aiming to evaluate anti-EGFR therapies retrospectively and prospectively.

scholarly journals The first evidence for SLFN11 expression as an independent prognostic factor for patients with esophageal cancer after chemoradiotherapy

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Takuma Kagami ◽  
Mihoko Yamade ◽  
Takahiro Suzuki ◽  
Takahiro Uotani ◽  
Shinya Tani ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Prognostic Value ◽  
Clinical Stage ◽  
In Vitro Study ◽  
Independent Prognostic Factor ◽  
Esophageal Function ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Highly Sensitive

Abstract Background Schlafen 11 (SLFN11) was recently identified as a dominant determinant of sensitivity to DNA-targeting agents including platinum-based drugs. SLFN11 also reportedly enhances cellular radiosensitivity. In this study, we examined the prognostic value of SLFN11 expression in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT), including the platinum derivative nedaplatin. Methods Seventy-three patients with ESCC who received dCRT were examined. SLFN11 expression was analyzed in pre-dCRT biopsies using immunohistochemistry and evaluated using a histo-score (H-score). Correlation between the H-score and overall survival was analyzed. An H-score ≥ 51 was provisionally defined as indicating high SLFN11 expression. Viability assays were performed using previously established isogenic human cell lines differentially expressing SLFN11 to test the usefulness of SLFN11 as marker of response to the dCRT regimen. Results High SLFN11 expression was independently associated with better prognosis in ESCC patients (hazard ratio = 0.295, 95% CI = 0.143–0.605, p = 0.001 for multivariate analysis). Kaplan-Meier survival curves showed that the prognostic value of high SLFN11 expression was most evident in patients at clinical stages II and III (p = 0.004). In in vitro study, SLFN11-proficient cells were highly sensitive to platinum derivatives compared to SLFN11-deficient cells. Conclusion SLFN11 expression is an independent prognostic factor for ESCC patients treated with dCRT and a potential biomarker for treatment selection of ESCC. Examination of SLFN11 may be particularly useful for clinical Stage II–III patients who wish to choose dCRT (instead of surgery) to preserve esophageal function.

MicroRNA expression profile in the N2 phenotype neutrophils of colorectal cancer and screen of putative key mircRNAs

2020 ◽  
Author(s):  
Liang Wang ◽  
Jun Yang ◽  
Jian Huang ◽  
Zheng-Qi Wen ◽  
Ning Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Expression Level ◽  
Cancer Tissue ◽  
Potential Biomarker

Abstract Objective: Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive tract, which accounts for 10% of all the malignant tumors in the world. The aim of this study was to identify key genes and miRNAs in CRC diagnosis, prognosis, and therapy and to further explore the potential molecular mechanisms of CRC.Methods: The infiltration and metastasis of neutrophils in Primary colorectal cancer tissue and Paracancerous tissue were observed by immunohistochemical staining. After inducing N2 neutrophils with TGF-β1 in vitro, exosomes were extracted and sequenced, and then the expression differences of microRNAs were screened by using Agilent microRNA microarrays. The data were imported to the Web CARMA for differential expression analysis. The GO and KEGG enrichment analysis were performed using DIANA-MirPath v3.0 using Targetscan database. And the corresponding targets were imported into Gephi for network analysis. The expression level of differentially expressed microRNA using quantitative Realtime polymerase chain reaction (RT-PCR) was validated.Results: A total of 2 miRNAs were found to be associated with N2 neutrophils, in which the expression of hsa-miR-4780 was upregulated and the expression of hsa-miR-3938 was downregulated in N2 neutrophils, compared with the neutrophils. In addition, the results of miRNA-targets networks showed that the hsa-mir-3938 and hsa-mir-4780 could regulate TUSC1 and ZNF197. The expression level of hsa-miR-4780 and hsa-miR-3938 were validated in accordance with the results of RT-PCR.Conclusion: The hsa-mir-3938 and hsa-mir-4780 were differentially expressed between N2 neutrophils and neutrophils. Moreover, the regulation of TUSC1 and ZNF197 by these DEmiRNA established the theoretical basis for the mechanism of N2 type neutrophils regulating the invasion and metastasis of CRC cells, and provided the potential biomarker for prognosis for clinical treatment of CRC

scholarly journals UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Chaohui Gu ◽  
Keyuan Zhao ◽  
Naichun Zhou ◽  
Feng Liu ◽  
Fei Xie ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Posttranscriptional Regulation ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Circular Rna ◽  
Cancer Proliferation ◽  
Lower Survival Rate ◽  
Protein Levels

Abstract Emerging evidences have demonstrated that ubiquitin-associated domain-containing protein 2 (UBAC2) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of UBAC2 in bladder cancer (BC) development have not been defined. In this study, we found that both UBAC2 mRNA and protein levels were upregulated in BC tissues and cell lines, and knockdown of UBAC2 inhibited BC cells proliferation both in vitro and in vivo. Meanwhile, Kaplan–Meier survival plots of 406 BC cases from TCGA database showed that higher expression of UBAC2 in BC patients was associated with lower survival rate. Mechanistic studies revealed that knockdown of UBAC2 increased the expression of p27 by posttranscriptional regulation. Our previous study indicated that circular RNA BCRC-3 (BCRC-3) promoted the expression of p27 through interacting with miR-182-5p, and reversed miR-182-5p-induced inhibition of p27 3′UTR activity. In the present study, we found that UBAC2 could bind to BCRC-3, and subsequently affected the interaction of BCRC-3 with miR-182-5p to inhibit the expression of p27. Furthermore, knockdown of BCRC-3 partly reversed the upregulation of p27 expression induced by knockdown of UBAC2. Our findings highlight a novel mechanism of UBAC2 in regulating p27 through affecting the function of BCRC-3, and provide a research basis for the diagnostic and therapeutic application of BC.

scholarly journals BIRC7 and STC2 Expression Are Associated With Tumorigenesis and Poor Outcome in Extrahepatic Cholangiocarcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382097167
Author(s):  
Jiequn Li ◽  
Zhulin Yang ◽  
Shengfu Huang ◽  
Daiqiang Li
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Diagnostic And Prognostic Application ◽  
Staining Technique ◽  
Clinicopathological Characteristics ◽  
Extrahepatic Cholangiocarcinoma ◽  
Node Metastasis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Prognostic Application

Background: Extrahepatic cholangiocarcinoma (EHCC) is a highly aggressive epithelial malignancy and has a poor prognosis for the insensitivity to therapies and difficulty in detection. Novel targets and biomarkers are urgently needed to develop for functional, diagnostic and prognostic application on EHCC. Methods: Immunohistochemical staining technique using the EnVision antibody complex was performed on the samples obtained from 100 EHCC, 30 peritumoral extrahepatic biliary tract (EHBT), 10 EHBT adenomas and 15 normal EHBT tissues. Results: The positive rates of BIRC7 and STC2 expression in tissues obtained from peritumoral EHBT, EHBT adenomas and normal EHBT were significantly lower than those in EHCC tissues. BIRC7 and STC2 proteins were expressed at significantly higher levels in patients with lymph node metastasis, invasion of adjacent tissues, and higher TNM stage (III and/or IV) and unable to undergo resection (biopsy only). Kaplan-Meier survival curves indicated that significantly decreased overall survival rate in patients with positive-BIRC7 or positive-STC2 expression compared with patients of negative-BIRC7 or negative-STC2 expression, respectively. Cox-proportional regression analysis demonstrated that positive-BIRC7 and positive-STC2 expression, along with poor differentiation of EHCC, tumor size >3 cm, lymph node metastasis, invasion of adjacent tissues and unable to undergo resection are independent prognostic factors of EHCC patients. Conclusions: The levels of BIRC7 and STC2 expression were correlated with clinicopathological characteristics of EHCC, and positive expression of BIRC7 and STC2 are associated with progression and poor clinical outcomes of EHCC. BIRC7 and STC2 might be a potential biomarker for EHCC in clinic.

scholarly journals The first evidence for SLFN11 expression as an independent prognostic factor for patients with esophageal cancer after chemoradiotherapy

2020 ◽  
Author(s):  
Takuma Kagami ◽  
Mihoko Yamade ◽  
Takahiro Suzuki ◽  
Takahiro Uotani ◽  
Shinya Tani ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Prognostic Value ◽  
Clinical Stage ◽  
In Vitro Study ◽  
Independent Prognostic Factor ◽  
Esophageal Function ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Highly Sensitive

Abstract Background: Schlafen 11 (SLFN11) was recently identified as a dominant determinant of sensitivity to DNA-targeting agents including platinum-based drugs. SLFN11 also reportedly enhances cellular radiosensitivity. In this study, we examined the prognostic value of SLFN11 expression in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT), including the platinum derivative nedaplatin. Methods: Seventy-three patients with ESCC who received dCRT were examined. SLFN11 expression was analyzed in pre-dCRT biopsies using immunohistochemistry and evaluated using a histo-score (H-score). Correlation between the H-score and overall survival was analyzed. An H-score ≥ 51 was provisionally defined as indicating high SLFN11 expression. Viability assays were performed using previously established isogenic human cell lines differentially expressing SLFN11 to test the usefulness of SLFN11 as marker of response to the dCRT regimen. Results: High SLFN11 expression was independently associated with better prognosis in ESCC patients (hazard ratio = 0.295, 95% CI = 0.143–0.605, p = 0.001 for multivariate analysis). Kaplan-Meier survival curves showed that the prognostic value of high SLFN11 expression was most evident in patients at clinical stages II and III (p = 0.004). In in vitro study, SLFN11-proficient cells were highly sensitive to platinum derivatives compared to SLFN11-deficient cells. Conclusion: SLFN11 expression is an independent prognostic factor for ESCC patients treated with dCRT and a potential biomarker for treatment selection of ESCC. Examination of SLFN11 may be particularly useful for clinical Stage II–III patients who wish to choose dCRT (instead of surgery) to preserve esophageal function.

scholarly journals XAGE-1b Promotes the Proliferation, Invasion and Metastasis of Gastric Cancer

2020 ◽  
Author(s):  
Hui Men ◽  
Zhi-wei Zhang ◽  
Gui-feng Lu ◽  
Shun Tan ◽  
Wen-Hui Hu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Survival Curve ◽  
Biological Marker ◽  
Invasion And Metastasis ◽  
Treatment Target ◽  
Kaplan Meier ◽  
Proliferation And Invasion

Abstract Background X antigen family member 1B (XAGE-1b), a member of XAGE subfamily and GAGE family, is upregulated in some malignant tumors and has been associated with the proliferation, invasion and metastasis of tumors. However, the biological roles of XAGE-1b in gastric cancer (GC) still remain unclear. Methods We detected the expression of XAGE-1b in 60 paired fresh tissues of GC patients by real-time RT-PCR. Kaplan-Meier survival curve was explored to analyze 5-year survival time of GC patients. Function experiments were performed to estimate the role of XAGE-1b on the proliferation, invasion and metastasis of GC cells. Informatic analysis was applied to investigate the potential mechanisms. Results XAGE-1b was obviously upregulated in GC tissues. XAGE-1b was correlated significantly with poor prognosis of GC patients. XAGE-1b markedly promoted the proliferation and invasion in GC cell lines in vitro. Knockdown of XAGE-1b promoted the pulmonary metastatic ability in nude mice. Moreover, XAGE-1b was positively or negatively correlated with the expression of CLDN6 and CHGA, which regulated the progression of GC. Conclusions XAGE-1b could act as an oncogene in GC, which provides a potential biological marker or treatment target for GC.

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