scholarly journals Combined detection of peripheral blood VEGF and inflammation biomarkers to evaluate the clinical response and prognostic prediction of non-operative ESCC

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuanyuan Ma ◽  
Xinyu Su ◽  
Xin Li ◽  
Xiaohui Zhi ◽  
Kan Jiang ◽  
...  

AbstractAn association between angiogenesis/inflammation status and tumor has been reported in various types of cancer. This study sought to assess the role of peripheral blood VEGF and some inflammation biomarkers in evaluating clinical response and prognosis in patients with non-operative esophageal squamous cell carcinoma (ESCC). Peripheral blood of 143 patients with non-operative ESCC at our institute was dynamically collected at 5 time points including 1 day before radiotherapy, during radiotherapy (15f), at the end of radiotherapy, 1 month after radiotherapy, and 3 months after radiotherapy. VEGF expression in the peripheral blood was detected and related inflammation biomarkers such as GPS, CAR and CLR were counted. Logistic regression and Cox regression were implemented respectively to analyze the correlation of each predictor with clinical response and prognosis. The performance of combined testing was estimated using AUCs. Based on independent predictors, a nomogram prediction model was established to predict the probabilities of 1- and 2-year PFS of patients. The effectiveness of the nomogram model was characterized by C-index, AUC, calibration curves and DCA. VEGF and CLR levels at the end of radiotherapy were independent predictors of clinical response, while VEGF and GPS levels at 3 months after radiotherapy were independent prognostic predictors. The efficacy of combined detection of VEGF and CLR is superior to the single detection in evaluating clinical response and prognosis. The nomogram showed excellent accuracy in predicting PFS. The combined detection of VEGF and CLR at the end of radiotherapy can be used to evaluate the clinical response of patients with non-operative ESCC, and the combined detection of VEGF and GPS 3 months after radiotherapy can be used to predict the prognosis. Implemented by nomogram model, it is expected to provide practical and reliable method to evaluate the clinical response and prognosis of patients with non-operative ESCC tool.

2021 ◽  
Author(s):  
Yuanyuan Ma ◽  
Xinyu Su ◽  
Xin Li ◽  
Xiaohui Zhi ◽  
Kan Jiang ◽  
...  

Abstract Objectives: An association between angiogenesis/inflammation status and tumor has been reported in various types of cancer. This study sought to assess the role of peripheral blood VEGF and some inflammation biomarkers in evaluating clinical response and prognosis in patients with non-operative esophageal squamous cell carcinoma (ESCC).Methods: Peripheral blood of 143 patients with non-operative ESCC at our institute was dynamically collected at 5 time points including 1 day before radiotherapy, during radiotherapy (15f), at the end of radiotherapy, 1 month after radiotherapy, and 3 months after radiotherapy. VEGF expression in the peripheral blood was detected and related inflammation biomarkers such as GPS, CAR and CLR were counted. Logistic regression and Cox regression were implemented respectively to analyze the correlation of each predictor with clinical response and prognosis. The performance of combined testing was estimated using AUCs. Based on independent predictors, a nomogram prediction model was established to predict the probabilities of 1- and 2-year PFS of patients. The effectiveness of the nomogram model was characterized by C-index, AUC, calibration curves and DCA.Results: VEGF and CLR levels at the end of radiotherapy were independent predictors of clinical response, while VEGF and GPS levels at 3 months after radiotherapy were independent prognostic predictors. The efficacy of combined detection of VEGF and CLR is superior to the single detection in evaluating clinical response and prognosis. The nomogram showed excellent accuracy in predicting PFS.Conclusions: The combined detection of VEGF and CLR at the end of radiotherapy can be used to evaluate the clinical response of patients with non-operative ESCC, and the combined detection of VEGF and GPS 3 months after radiotherapy can be used to predict the prognosis. Implemented by nomogram model, it is expected to provide practical and reliable method to evaluate the clinical response and prognosis of patients with non-operative ESCC tool.


Author(s):  
Zhengdong Deng ◽  
Xiangyu Li ◽  
Yuanxin Shi ◽  
Yun Lu ◽  
Wei Yao ◽  
...  

Autophagy is an important bioprocess throughout the occurrence and development of cancer. However, the role of autophagy-related lncRNAs in pancreatic cancer (PC) remains obscure. In the study, we identified the autophagy-related lncRNAs (ARlncRNAs) and divided the PC patients from The Cancer Genome Atlas into training and validation set. Firstly, we constructed a signature in the training set by the least absolute shrinkage and selection operator penalized cox regression analysis and the multivariate cox regression analysis. Then, we validated the independent prognostic role of the risk signature in both training and validation set with survival analysis, receiver operating characteristic analysis, and Cox regression. The nomogram was established to demonstrate the predictive power of the signature. Moreover, high risk scores were significantly correlated to worse outcomes and severe clinical characteristics. The Pearson’s analysis between risk scores with immune cells infiltration, tumor mutation burden, and the expression level of chemotherapy target molecules indicated that the signature could predict efficacy of immunotherapy and targeted therapy. Next, we constructed an lncRNA–miRNA–mRNA regulatory network and identified several potential small molecule drugs in the Connectivity Map (CMap). What’s more, quantitative real-time PCR (qRT-PCR) analysis showed that serum LINC01559 could serve as a diagnostic biomarker. In vitro analysis showed inhibition of LINC01559 suppressed PC cell proliferation, migration, and invasion. Additionally, silencing LINC01559 suppressed gemcitabine-induced autophagy and promoted the sensitivity of PC cells to gemcitabine. In conclusion, we identified a novel ARlncRNAs signature with valuable clinical utility for reliable prognostic prediction and personalized treatment of PC patients. And inhibition of LINC01559 might be a novel strategy to overcome chemoresistance.


2020 ◽  
Vol 19 ◽  
pp. 153303382096212
Author(s):  
Yuqi Sun ◽  
Peng Peng ◽  
Lanlan He ◽  
Xueren Gao

The purpose of this study was to identify long noncoding RNAs (lncRNAs) related to prognosis of patients with colorectal cancer (CRC) and develop a prognostic prediction model for CRC. Transcriptome data and survival information of CRC patients were downloaded from The Cancer Genome Atlas. The differentially expressed lncRNAs (DElncRNAs) between CRC and normal colorectal tissues were identified by the edgeR package. The association of DElncRNAs expression with prognosis of CRC patients was analyzed by the survival package. A nomogram predicting 3- and 5- year overall survival of CRC patients was drawn by the rms package. A total of 1046 DElncRNAs were identified, including 271 down-regulated and 775 up-regulated lncRNAs in CRC. Multivariate Cox regression analysis showed 10 lncRNAs related to the prognosis of CRC patients. Thereinto high expression of AC004009.1, LHX1-DT, ELFN1-AS1, AL136307.1, AC087379.2, RBAKDN and AC078820.1 was associated with poorer prognosis of CRC patients. High expression of LINC01055, AL590483.1 and AC008514.1 was associated with better prognosis of CRC patients. Furthermore, the risk score model developed based on the 10 lncRNAs could effectively predict overall survival of CRC patients. In conclusion, 10 prognostic biomarkers for CRC were identified, which would be helpful to understand the role of lncRNAs in CRC progression.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3983-3983 ◽  
Author(s):  
Meral Beksac ◽  
Mehmet Gunduz ◽  
Mehmet Ozen ◽  
Sule Mine Bakanay Ozturk ◽  
Ozlem Kucuk ◽  
...  

Abstract Background and Aim: PET is a useful tool that allows deeper assessment of response beyond that measured by M protein levels. It has been reported to predict outcome following both ASCT and recently non-transplant setting too. To be able to integrate PET-CT negativity to internationally accepted response criteria the cut-off level needs to be validated by independent investigators. This prospective study was initiated to elucidate the prognostic role of PET-CT in the ASCT setting testing the cut-off level 4.2 initially reported by Zamagniet al versus the cut-off (3.35) based on our results. Patients and Methods: 139 consecutive patients diagnosed and transplanted in Ankara University with pre- and post-transplant (Tx) PET-CT imaging were included. Patients were: Median age 56.5 +/- 8.7 (M/F: 79/60), ISS I/II/III: 50/55/34, renal impairment (10.8%), bone involvement (90.6%), del13q (40.9%), t(4;14) and/or p53(26.5%), LDH high(12.9%), induction with Bortezomib (73.4%). Pre-Tx clinical response ³VGPR: 52.9%, post-Tx clinical response ³VGPR: 77.5%. Overall Survival (OS): median: 33 months (4.2-141 months). PASW statistics for Windows program was used for statistical analysis. Results: ROC analysis revealed 3.35 as a significant cut-off level (p=0.005; OS). PET-CR was defined FDG uptake less than 4.2 or 3.35 depending on the analysis. Pre-Tx PET-CR:17.4%, post-Tx PET-CR: 69.6% (<4.2), 46.4% (<3.35). Cross tabulation of post-Tx clinical response versus PET response is summarized in Table 1. PET (>4.2) was predictive for PFS (p=0.05) but not OS (p=0.096). However PET (>3.35) was predictive for OS (p=0.037) but not PFS. PET (>4.2) was predictive for OS (p=0.014) and PFS (p=0.019)among only ³VGPR patients. Similarly PET (>3.35) among ³VGPR patients was also predictive for OS (p=0.05) and PFS (p=0.04). PET-CR was not predictive among ³CR patients significantly. Cox regression analysis for PFS, when PET (>4.2) is used, ISS was significant only (OR: 1.99, p=0.049) when post-Tx clinical response (OR: 0.46, p=0.022) is not included in the model. For OS, clinical response both pre-Tx (OR: 0.35, p=0.015) and post-Tx (OR: 0.18, p<0.001) is the only significant parameter. PET (>3.35) increased the predictive value of PET. In addition to clinical response, PET-CR appeared as a borderline significant factor for OS: pre-Tx (OR: 2.2, p=0.078), post-Tx (OR: 2.26, p=0.067). In conclusion both PET (<4.2) and PET (<3.35) recognizes deeper responses as manifested by extension of PFS (PET<4.2) and OS (PET<3.35). Both assessments were able to define patients with separate survival outcomes within the ³VGPR group. This effect could not be confirmed within the ³CR group due to the relatively smaller sample size. After multivariate analysis only PET (>3.35) approached significance. To be able to integrate PET-CR to response criteria definition of PET-CR needs to be confirmed. Table 1PET cut-off 4.2PET cut-off 3.35Number of patientsnegativepositivenegativepositive<PR2020PR155911VGPR39143122CR22141521< VGPR17511113 VGPR61284643< CR561942333 CR221415213 year PFS45.8%25.6%48.9%28.9%3 year OS91.6%76.1%94.9%79.5% Figure-1: PET(<3.35) and OS Figure-1:. PET(<3.35) and OS Figure-2. PET(<3.35) and OS within the ³VGPR patients Figure-2. PET(<3.35) and OS within the ³VGPR patients Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Heike Loeser ◽  
Matthias Scholz ◽  
Hans Fuchs ◽  
Ahlem Essakly ◽  
Alexander Iannos Damanakis ◽  
...  

Abstract Valid biomarkers for a better prognostic prediction of the clinical course in esophageal adenocarcinoma (EAC) are still not implemented. Integrin alpha V (ITGAV), a transmembrane glycoprotein responsible for cell-to-matrix binding has been found to enhance tumor progression in several tumor entities. The expression pattern and biological role of ITGAV expression in esophageal adenocarcinoma (EAC) has not been analyzed so far. Aim of the study is to evaluate the expression level of ITGAV in a very large collective of EAC and its impact on individual patients´ prognosis. 585 patients with esophageal adenocarcinoma were analyzed immunohistochemically for ITGAV. The data was correlated with clinical, pathological and molecular data (TP53, HER2/neu, c-myc, GATA6, PIK3CA and KRAS). A total of 85 patients (14.3%) out of 585 analyzable tumors showed an ITGAV expression and intratumoral heterogeneity was low. ITGAV expression was correlated with a shortened overall-survival in the patients´ group that underwent primary surgery (p = 0.014) but not in the group of patients that received neoadjuvant treatment before surgery. No correlation between any of the analyzed molecular marker (mutations or amplifications) (TP53, HER2, c-myc, GATA6, PIK3CA and KRAS) and ITGAV expression could be observed. A multivariate cox-regression model was performed which showed tumor stage, lymph node metastasis and ITGAV expression as independent prognostic markers for overall-survival in the group of patients without neoadjuvant treatment. ITGAV expression is correlated with an impaired patient outcome in the group of patients without neoadjuvant therapy and serves as a prognostic factor in EAC.


1973 ◽  
Vol 29 (02) ◽  
pp. 353-362
Author(s):  
J Lisiewicz ◽  
A Pituch ◽  
J. A Litwin

SummaryThe local Sanarelli-Shwartzman phenomenon (SSP-L) in the skin of 30 rats was induced by an intr a cutaneous sensitizing injection of leukaemic leucocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL), acute myeloblastic leukaemia (AL) and chronic granulocytic leukaemia (CGL) and challenged by an intravenous injection of 100(μ of E. coli endotoxin. SSP-L was observed in 7 rats after injection of CLL lymphocytes and in 6 and 2 rats after AL myeloblasts and the CGL granulocytes, respectively. The lesions in the skin after AL myeloblasts appeared in a shorter time and were of longer duration compared with those observed after CLL lymphocytes and CGL granulocytes. Histologically, the lesions consisted of areas of destruction in the superficial layers of the skin ; the demarcation line showed the presence of neutrophils, macrophages and erythrocytes. Haemorrhages and fibrin deposits near the demarcation line were larger after injection of CLL lymphocytes and AL myeloblasts than after CGL granulocytes. The possible role of leucocyte procoagulative substances in the differences observed have been discussed.


2018 ◽  
Vol 25 (35) ◽  
pp. 4535-4544 ◽  
Author(s):  
Annalisa Ruggeri ◽  
Annalisa Paviglianiti ◽  
Fernanda Volt ◽  
Chantal Kenzey ◽  
Hanadi Rafii ◽  
...  

Background: Circulating endothelial cells (CECs), originated form endothelial progenitors (EPCs) are mature cells not associated with vessel walls and detached from the endothelium. Normally, they are present in insignificant amounts in the peripheral blood of healthy individuals. On the other hand, elevated CECs and EPCs levels have been reported in the peripheral blood of patients with different types of cancers and other diseases. Objective: This review aims to provide an overview on the characterization of CECs and EPCs, to describe isolation methods and to identify the potential role of these cells in hematological diseases and hematopoietic stem cell transplantation. Methods: We performed a detailed search of peer-reviewed literature using keywords related to CECs, EPCs, allogeneic hematopoietic stem cell transplantation, and hematological diseases (hemoglobinopathies, hodgkin and non-hodgkin lymphoma, acute leukemia, myeloproliferative syndromes, chronic lymphocytic leukemia). Results: CECs and EPCs are potential biomarkers for several clinical conditions involving endothelial turnover and remodeling, such as in hematological diseases. These cells may be involved in disease progression and in the neoplastic process. Moreover, CECs and EPCs are probably involved in endothelial damage which is a marker of several complications following allogeneic hematopoietic stem cell transplantation. Conclusion: This review provides information about the role of CECs and EPCs in hematological malignancies and shows their implication in predicting disease activity as well as improving HSCT outcomes.


2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.


2021 ◽  
Vol 15 (1) ◽  
pp. 43-55
Author(s):  
Chao Yuan ◽  
Hongjun Yuan ◽  
Li Chen ◽  
Miaomiao Sheng ◽  
Wenru Tang

Background: Triple-negative breast cancer (TNBC) is characterized by fast tumor increase, rapid recurrence and natural metastasis. We aimed to identify a genetic signature for predicting the prognosis of TNBC. Materials & methods: We conducted a weighted correlation network analysis of datasets from the Gene Expression Omnibus. Multivariate Cox regression was used to construct a risk score model. Results: The multi-factor risk scoring model was meaningfully associated with the prognosis of patients with TBNC. The predictive power of the model was demonstrated by the time-dependent receiver operating characteristic curve and Kaplan–Meier curve, and verified using a validation set. Conclusion: We established a long noncoding RNA-based model for the prognostic prediction of TNBC.


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