scholarly journals Chemokine (C-X-C motif) ligand 1 is associated with tumor progression and poor prognosis in patients with colorectal cancer

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Changhua Zhuo ◽  
Xianyi Wu ◽  
Jing Li ◽  
Dan Hu ◽  
Jinliang Jian ◽  
...  

Chemokine (C-X-C motif) ligand 1 (CXCL1) is a chemotactic cytokine known to regulate cancer progression and invasion. However, the prognostic significance of CXCL1 expression in colorectal cancer (CRC) has not been fully characterized. The present study explored the clinicopathological significance and potential role of CXCL1 in the carcinogenesis and progression of CRC. The protein expression of CXCL1 was measured immunohistochemically in tissue microarrays constructed from 276 CRC patients. CXCL1 expression levels and their associations with clinicopathological characteristics and patient survival were evaluated. The effect of CXCL1 on glycolysis was also examined. High CXCL1 expression was detected in 165 (59.8%) cases. CXCL1 expression was correlated with tumor diameter (P=0.002), T stage (P=0.044), N stage (P=0.005), M stage (P=0.001), lymphovascular invasion (P=0.010), and carcinoembryonic antigen status (P=0.019). High CXCL1 expression was validated as an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) by both univariate and multivariate Cox regression analyses (both P<0.05). Experimentally, expression of CXCL1 was knocked down by stable transfected short hairpin RNA, resulting in a significantly decreased rate of glycolysis both in in vitro assays and in patients’ samples (P<0.05). Silencing the expression of CXCL1 decreased the levels of the glycolytic enzymes GLUT1, HK2, and LDHA. In conclusion, by inducing glycolysis, CXCL1 plays a crucial role in both cancer progression and metastasis in CRC patients. The CXCL1 expression level is an independent prognostic factor for both OS and DFS. Moreover, CXCL1 may serve as a new biomarker and potential therapeutic target for CRC treatment.

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Rui Xu ◽  
Junhao You ◽  
Fang Li ◽  
Bing Yan

Purpose. The relationship between high blood glucose and colorectal cancer (CRC) has been studied, but the role of postoperative fasting blood glucose (FBG) in patients with a prior normal FBG has never been addressed. Methods. A total of 120 CRC patients staged I-III were enrolled, and the prognostic value of postoperative FBG for disease-free survival (DFS) was determined by Kaplan-Meier analysis. Univariate and multivariate analyses were conducted to test other clinicopathological parameters, including preoperative hemoglobin (HGB) and the neutrophil-lymphocyte ratio (NLR). Results. By a cut-off point of 5.11 mmol/L, 51 and 69 patients were divided into low postoperative FBG (<5.11 mmol/L) and high postoperative FBG (≥5.11 mmol/L) groups, respectively. A high postoperative FBG was more common in older age (P=0.01), left-located tumor (P=0.02), smaller tumor diameter (P=0.01), node negative involvement (P=0.01), lesser positive lymph nodes (P=0.02), and high preoperative HGB (P=0.01). Further, high postoperative FBG patients displayed a significantly better DFS than low postoperative FBG patients (48.80±22.12 months vs. 40.06±24.36 months, P=0.04), but it was less likely to be an independent prognostic factor. Conclusions. Postoperative FBG plays a temporal prognostic role for patients with stage I-III CRC with a prior normal FBG, but it is not an independent prognostic factor.


2020 ◽  
Author(s):  
Ting li ◽  
Wenjia Hui ◽  
Halina Halike ◽  
Feng Gao

Abstract Background: Colorectalcancer (CRC) is a prevalent gastrointestinal tumor with high incidence and mortality. Dysregulation of RNA binding proteins (RBPs) has been found in a variety of cancers and is related to oncogenesis and progression. This study aimed to develop and validate new biomarkers related to CRC prognosis by a series of bioinformatics analysis.Methods: We mined the gene expression data of 510 CRC samples from The Cancer Genome Atlas (TCGA) database, differentially expressed genes were screened and prognosis-related genes were identified. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were carried out. A prognosis-related gene signature was constructed by univariate and multivariate Cox analysis. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves were utilized to evaluate the signature,The test set was used to validate the RBPs risk score model.Survival analysis was carried out to determine the independent prognostic significance of the signature. A nomogram combined with the gene signature was constructed.Results: A total of 224 aberrantly expressed RBPs were obtained, comprising 78 downregulated and 146 upregulatedRBPs. 13 RBPs with p < 0.005 were revealed in univariateCox regression analysis of train group, then stepwise multivariate Cox regression was applied for constituting an eight- RBP (BRCA1, TERT, TDRD7, PPARGC1A, LUZP4, CELF4, ZC3H12C, PNLDC1) signature prognostic biomarkers. Further analysis demonstrated that high risk score for patients was significantly related to poor overall survival according to the model. The area under the time-dependent receiver operator characteristic curve of the prognostic model was 0.730 at 5 years. The signature-based risk score was an independent prognostic factor in CRC patients. We also established a nomogram based on eight RBPs and internal validation in the train set, which displayed a favorable discriminating ability for Colorectal cancer.Conclusions: The established eight-RBP signature may serve as a novel independent prognostic factor that could be an important tool to predict the prognostic outcome of CRC patients. However, the specific biological mechanism needs further verification.


2020 ◽  
Author(s):  
Hou-Qun Ying ◽  
Fan Sun ◽  
Wei Wang ◽  
Dan Cai ◽  
Ying Yang ◽  
...  

Abstract Background Evaluating chronic inflammation in colorectal cancer (CRC) may aid in identifying patients at the highest risk of recurrence or progression, and help inform clinical treatment decisions. Here, we report the effect of fibrinogen to pre-albumin ratio (FPR) in determining response to chemotherapy and reveal outcomes in CRC patients. Methods A total of 2917 eligible CRC patients from multiple-centers were enrolled, and the outcome of these patients was obtained by three years’ follow-up. Circulating fibrinogen, albumin, pre-albumin, CEA, CA199 and FPR were detected and calculated in these patients. Kaplan-Meier curves, Cox regression, time-dependent ROC, Harrell’s concordance index, calibration and decision curves were used to investigate the role of FPR in clinical outcome of CRC patients. Results Our results reveal significantly inferior outcomes in right- than left-sided patients with advanced CRC (stage III and IV), with preoperative FPR found to be a robust and independent prognostic factor for CRC at each stage. Moreover, prognostic nomograms, including FPR, effectively predicted clinical outcomes of the patients. Furthermore, preoperative FPR was significantly associated with chemotherapy efficacy. Specifically, low-grade (FPR < 15) and medium-grade (15 ≤ FPR < 20) FPR patients exhibited complete response to chemotherapy and attenuated chemosensitivity, respectively, whereas high-grade inflammation (FPR ≥ 20) conferred resistance to the treatment. Conclusion CRC-related inflammation affects response to chemotherapy and the resultant clinical outcomes. Circulating FPR is a simple, economically-friendly and robust independent prognostic factor for effectively predicting outcomes of CRC patients. Targeting chronic inflammation and its corresponding signaling pathway, coupled with measuring FPR, presents a novel approach for clinical management of CRC.


2019 ◽  
Vol 8 (10) ◽  
pp. 1647 ◽  
Author(s):  
Sachiyo Onishi ◽  
Masahiro Tajika ◽  
Tsutomu Tanaka ◽  
Yutaka Hirayama ◽  
Kazuo Hara ◽  
...  

The prognostic significance of sarcopenia in unresectable advanced esophageal cancer remains unclear. Our study retrospectively evaluated 176 consecutive Japanese patients with esophageal squamous cell carcinoma who had been diagnosed with unresectable advanced cancer in Aichi Cancer Center Hospital between January 2007 and December 2014. Skeletal muscle mass was calculated from abdominal computed tomography (CT) scans before treatment, and patients were divided into sarcopenic and non-sarcopenic groups. Sarcopenia was present in 101 patients (57.4%). Eighty-two patients in the sarcopenic group and 63 patients in the non-sarcopenic group died during follow-up (mean: 20.3 months). The overall survival (OS) rate was significantly lower in the sarcopenic group compared to the non-sarcopenic group (2-year OS: 9.8% vs. 23.7%, p < 0.01). Cox regression analysis revealed only pretreatment sarcopenia as an independent prognostic factor (hazard ratio (HR): 1.48, 95% confidence interval (CI): 1.04–2.10, p = 0.03). In the sarcopenic group, withdrawn cases, for whom the planned treatment was discontinued for some reason, showed a significantly lower OS rate compared to complete cases (1-year OS: 11.0% vs. 59.9%, p < 0.01). The most common reason for discontinuation was aspiration pneumonia (64.5%). Presence of sarcopenia was an independent prognostic factor for unresectable advanced esophageal cancer. Identifying the presence of sarcopenia prior to treatment may improve the prognosis.


2019 ◽  
Vol 8 (11) ◽  
pp. 1903 ◽  
Author(s):  
Eun kyo Joung ◽  
Jiyoung Kim ◽  
Nara Yoon ◽  
Lee-so Maeng ◽  
Ji Hoon Kim ◽  
...  

Background: The prognostic role of the translational factor, elongation factor-1 alpha 1 (EEF1A1), in colon cancer is unclear. Objectives: The present study aimed to investigate the expression of EEF1A in tissues obtained from patients with stage II and III colon cancer and analyze its association with patient prognosis. Methods: A total of 281 patients with colon cancer who underwent curative resection were analyzed according to EEF1A1 expression. Results: The five-year overall survival in the high-EEF1A1 group was 87.7%, whereas it was 65.6% in the low-EEF1A1 expression group (hazard ratio (HR) 2.47, 95% confidence interval (CI) 1.38–4.44, p = 0.002). The five-year disease-free survival of patients with high EEF1A1 expression was 82.5%, which was longer than the rate of 55.4% observed for patients with low EEF1A1 expression (HR 2.94, 95% CI 1.72–5.04, p < 0.001). Univariate Cox regression analysis indicated that age, preoperative carcinoembryonic antigen level, adjuvant treatment, total number of metastatic lymph nodes, and EEF1A1 expression level were significant prognostic factors for death. In multivariate analysis, expression of EEF1A1 was an independent prognostic factor associated with death (HR 3.01, 95% CI 1.636–5.543, p < 0.001). EEF1A1 expression was also an independent prognostic factor for disease-free survival in multivariate analysis (HR 2.54, 95% CI 1.459–4.434, p < 0.001). Conclusions: Our study demonstrated that high expression of EEF1A1 has a favorable prognostic effect on patients with colon adenocarcinoma.


Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 149 ◽  
Author(s):  
Katarzyna Aleksandra Kujawa ◽  
Ewa Zembala-Nożyńska ◽  
Alexander Jorge Cortez ◽  
Tomasz Kujawa ◽  
Jolanta Kupryjańczyk ◽  
...  

Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan–Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan–Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02–4.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (χ2 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and/or may indicate fallopian–epithelial origin of the tumor.


Author(s):  
Michael Stotz ◽  
Joanna Szkandera ◽  
Tatjana Stojakovic ◽  
Julia Seidel ◽  
Hellmut Samonigg ◽  
...  

AbstractIntra-tumoral macrophages have been involved as important players in the pathogenesis and progression of cancer. Recently, inflammatory parameters of the systemic inflammatory response have also been proposed as usefully prognostic biomarkers. One of these, the lymphocyte to monocyte ratio (LMR) in peripheral blood has been shown as a prognostic factor in hematologic and some solid tumors. In this study we analyzed for the first time the prognostic value of LMR in a large middle European cohort of pancreatic cancer (PC) patients.Data from 474 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Cancer-specific survival (CSS) was analyzed using the Kaplan-Meier method. To further evaluate the prognostic significance of the LMR, univariate and multivariate Cox regression models were calculated.Increased LMR at diagnosis was significantly associated with well-established prognostic factors, including high tumor stage and tumor grade (p<0.05). In univariate analysis, we observed that an increased LMR was a significant factor for better CSS in PC patients (HR 0.70; 95% CI 0.57–0.85; p<0.001). In multivariate analysis including age, Karnofsky Index, tumor grade, tumor stage, administration of chemotherapy, LMR and surgical resection, we confirmed increased LMR as an independent prognostic factor for CSS (HR 0.81; 95% CI 0.66–0.99; p=0.04).In conclusion, we identified LMR as an independent prognostic factor in PC patients. Our results indicate that the LMR might represent a novel and useful marker for patient stratification in PC management.


Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 967
Author(s):  
María I. Aroca-Siendones ◽  
Sara Moreno-SanJuan ◽  
Jose D. Puentes-Pardo ◽  
Michela Verbeni ◽  
Javier Arnedo ◽  
...  

Colorectal cancer (CRC) is one of the most common tumours in developed countries. Although its incidence and mortality rates have decreased, its prognosis has not changed, and a high percentage of patients with CRC develop relapse (metachronous metastasis, MM, or local recurrence, LR) during their disease. The identification of these patients is very important for their correct management, but the lack of prognostic markers makes it difficult. Given the connection between circadian disruption and cancer development and progression, we aimed to analyse the prognostic significance of core circadian proteins in CRC. We measured the expression of PER1-3, CRY1-2, BMAL1 and NR1D2 in a cohort of CRC patients by immunohistochemistry (IHC) and analysed their prognostic potential in this disease. A low expression of PER2 and BMAL1 was significantly associated with metastasis at the moment of disease diagnosis, whereas a high expression of CRY1 appeared as an independent prognostic factor of MM development. A high expression of NR1D2 appeared as an independent prognostic factor of LR development after disease diagnosis. Moreover, patients with a low expression of BMAL1 and a high expression of CRY1 showed lower OS and DFS at five years. Although these markers need to be validated in larger and different ethnic cohorts, the simplicity of IHC makes these proteins candidates for personalizing CRC treatment.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yuan Ding ◽  
Zhongquan Sun ◽  
Sitong Zhang ◽  
Yanjie Li ◽  
Xin Han ◽  
...  

Hepatocellular carcinoma (HCC) is one of the most common and aggressive tumors in the world while the accuracy of the present tests for detecting HCC is poor. A novel diagnostic and prognostic biomarker for HCC is urgently needed. Overwhelming evidence has demonstrated the regulatory roles of small nucleolar RNA (snoRNA) in carcinogenesis. This study is aimed at analyzing the expression of a snoRNA, SNORA52, in HCC and exploring the correlation between its expression and various clinical characteristics of HCC patients. By using quantitative real-time PCR, we found that SNORA52 was downregulated in HCC cell lines ( P < 0.05 ) and HCC tissues ( P < 0.001 ). Correlation analysis showed that the expression of SNORA52 was obviously associated with tumor size ( P = 0.011 ), lesion number ( P = 0.007 ), capsular invasion ( P = 0.011 ), tumor differentiation degree ( P = 0.046 ), and TNM stage ( P = 0.004 ). The disease-free survival (DFS) and overall survival (OS) analysis showed that patients with lower SNORA52 expression had a worse prognosis ( P < 0.001 ). Univariate and multivariate Cox regression analysis showed that SNORA52 expression was a completely independent prognostic factor to predict DFS ( P = 0.009 ) and OS ( P = 0.012 ) of HCC patients. Overall, our findings showed SNORA52 expression levels were downregulated in HCC tissues and correlated with multiple clinical variables, and SNORA52 was an independent prognostic factor for HCC patients, which suggested that SNORA52 could function as a potential diagnostic and prognostic biomarker for HCC patients.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15647-e15647
Author(s):  
Minglin Lin ◽  
Weijia Liao ◽  
Junfei Jin

e15647 Background:Neutral sphingomyelinase 1 (NSMase1) catalyzes sphingomyelin to generate ceramide and mediates tumor cell apoptosis; however, the roles of NSMase1 in hepatocellular carcinoma (HCC) remain unclear. This study aims to evaluate the clinical value and prognostic significance of NSMase1 in HCC. Methods:A total of 142 patients who underwent radical hepatectomy were involved in this study. The expression of NSMase1 in HCC tissues and adjacent nontumorous liver tissues (ANLTs) was detected by quantitative real-time polymerase chain reaction and immunohistochemistry, and the association between NSMase1 expression and clinicopathologic features as well as prognosis of HCC patients was analyzed. Univariate and multivariate analyses were applied to identify independent prognostic factors. Results: NSMase1, at both mRNA and protein levels, was significantly decreased in HCC tissues compared to ANLTs. Low NSMase1 expression was associated with tumor size ( P= 0.029), TNM stage ( P= 0.040) and recurrence ( P= 0.006). Statistically, both the overall survival (OS) and disease-free survival (DFS) of low NSMase1 expression group were significantly shorter compared with high NSMase1 expression group ( p= 0.001; p= 0.001; respectively). Remarkably, the multivariate analysis showed that the low NSMase1 expression was an independent prognostic factor for OS (hazard ratio = 1.840; 95% confidence interval, 1.178-2.875, P= 0.007) and DFS (hazard ratio = 1.706; 95% confidence interval, 1.096-2.655, P= 0.018) in all enrolled HCC patients. Conclusions: NSMase1 down-regulation might actually serve as an independent prognostic factor for HCC patients. However, the roles of “NSMase1-ceramide” metabolic network in HCC deserve further studies.


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