scholarly journals YAP Levels Combined with Plasma CEA Levels Are Prognostic Biomarkers for Early-Clinical-Stage Patients of Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Zihui Xu ◽  
Hui Wang ◽  
Ling Gao ◽  
Hongfeng Zhang ◽  
Xiangyang Wang

Background. Colorectal cancer (CRC) is one of the most common cancers worldwide. Surgical operation is routinely applied to patients with CRC. An important part of postoperative care for patients is to assess the prognosis of patients, especially those with early-stage cancers. However, effective biomarkers for CRC prognosis remain inadequate. The purpose of this study was to assess the prognostic potential of Yes-associated protein (YAP) and carcinoembryonic antigen (CEA) in early-stage CRC. Methods. A total of 116 matched pairs of CRC tissues and adjacent normal mucosae as well as 73 cases of metastatic lymph nodes were analyzed. Results. The results show that CRC tissues exhibited higher YAP expression compared with the adjacent normal mucosae. Immunohistochemical analysis shows that YAP expression in the CRC or lymphatic metastatic tissues was clearly higher than that in normal mucosae (P<0.01), whereas that in CRC tissues with lymphatic metastasis was higher than that in tissues without lymphatic metastasis (P<0.05). YAP expression is associated with serosal invasion, lymphatic metastasis, lymph node ratio, remote metastasis, Dukes stage, and CEA levels (P<0.05). YAP and CEA are independent predictors of the survival of CRC patients (P<0.05 and P<0.01). YAP predicted CRC prognosis primarily for patients with late-clinical-stage CRC (P=0.002), but not for patients with early-clinical-stage CRC (P=0.083). However, patients with high YAP and high CEA levels exhibited lower overall survival rates than those with low YAP expression in early-clinical-stage CRC (P<0.001). Conclusion. High YAP levels in the cancer tissues combined with high plasma CEA levels are potential biomarkers for predicting CRC prognosis in the early clinical stage.

2005 ◽  
Vol 1 (1) ◽  
pp. 51-57 ◽  
Author(s):  
David M Robertson ◽  
Martin K Oehler

Ovarian cancer is the most lethal gynecological malignancy as it is diagnosed at a late clinical stage in more than 80% of patients. The development of diagnostic tests that can detect all types of ovarian cancers with high specificity and sensitivity, and at an early stage would improve survival rates. Serum inhibin is an ovarian hormone involved in the regulation of fertility, decreasing to undetectable levels after menopause. Certain ovarian malignancies, such as mucinous carcinomas and granulosa cell tumors, continue to produce inhibin, which is detectable in serum. A test for serum inhibin has been developed which is able to diagnose granulosa cell tumors and mucinous carcinomas with high accuracy. When the inhibin assay is used in conjunction with the CA125 test, which detects epithelial ovarian carcinomas, the two tests detect the majority of ovarian cancers with high sensitivity (95%) and specificity (95%). This article discusses the application of the inhibin test in ovarian cancer.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15548-e15548
Author(s):  
Ritvi K Bagadia ◽  
Vishal Uchila Shishir Rao ◽  
Ajay Balakrishnan ◽  
Abhijith George ◽  
Prashant Kumar

e15548 Background: Around 90% of cancer-related mortalities are caused by tumor metastasis. CTC clusters, which constitute an intermediate stage of metastasis, have not been studied extensively in head & neck cancers. The mortality rate of oral cancers remains alarmingly high, despite multimodality treatment. The aim of the study is to identify the presence of CTC clusters in patients with Oral Squamous Cell Carcinoma (OSCC) and to correlate their presence with clinical and pathological factors. Methods: Fifty patients diagnosed with histologically proven OSCC, treatment naïve, and underwent surgery at HCG Cancer Centre, Bangalore, were consented and enrolled in the study. An IRB-approved protocol allowed for the collection of 10 ml of blood from central (jugular) and peripheral veins intra-operatively, prior to tumor removal. The culturing of CTC clusters was done using ellipsoidal microwell plates maintained at hypoxic conditions, at the Institute of Bioinformatics, Bangalore. After fourteen days of culturing, the cells were fixed and stained for DAPI, Pan-CK and CD45. The CTC clusters were classified into Loose, Tight and very Tight based on the median gray values obtained from DAPI staining on ImageJ software. Clinical data was collected from patient records and subjected to analysis using Descriptive statistics. Results: From the 50 patients included in the study, 22 (44%) patients exhibited tight clusters in central blood, while only 13 (26%) patients exhibited tight clusters in peripheral blood. A higher clinical stage was observed in a greater percentage of patients with tight clusters in central blood (early: 45.5% versus late: 54.5%), but the same findings could not be inferred with pathological staging (early stage: 59.1% versus late stage: 40.1%). No significant correlation with adverse pathological features was noted. Conclusions: This observational study provides an insight into the varying biological behaviours of similarly grouped cancers, which is based on the standard TNM staging. The study forms the basis for the hypothesis of tight clusters in the central and peripheral circulation, correlating with loco-regional and distant metastasis respectively, thus leading to poorer disease-free and overall survival rates.


1991 ◽  
Vol 37 (12) ◽  
pp. 2081-2086 ◽  
Author(s):  
Tetsuya Tachikawa ◽  
Shin Yazawa ◽  
Takayuki Asao ◽  
Sadahito Shin ◽  
Noboru Yanaihara

Abstract A novel method has been developed to quantify α(1→3)-L-fucosyltransferase activity in human sera by applying a sandwich-type immunoradiometric assay. H type 2 trisaccharide (6Fuc α 1→2Gal beta 1→4GlcNAc) covalently attached to bovine serum albumin (BSA) was used as an acceptor and incubated with serum samples in the presence of guanosine diphosphate-fucose. The resulting product, Y tetrasaccharide (Fuc α 1→2Gal beta 1→4[Fuc α 1→3] GlcNAc beta-BSA), was detected by a sequential use of anti-BSA antibody-coated bead and 125I-labeled anti-Y antibody. Inter- and intra-assay CVs for α(1→3)-L-fucosyltransferase were both less than 4%, and the results of the dilution linearity and analytical recovery studies were satisfactory. Using the present assay method, we measured α(1→3)-L-fucosyltransferase in serum from patients with benign and malignant gastric disorders and in healthy subjects. The detection rate of α(1→3)-L-fucosyltransferase for cancer was apparently higher than that of carcinoembryonic antigen measured in the same samples, particularly in the early clinical stage; indeed, no correlation was observed between the concentrations of the two potential markers. The results indicate that the present assay method seems to be excellent for the determination of serum α(1→3)-L-fucosyltransferase activity and useful for the detection of cancer-associated increases of the enzyme activity at the early stage of gastric cancer.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yoon Ho Ko ◽  
Young-Seok Cho ◽  
Hye Sung Won ◽  
Ho Jung An ◽  
Der Sheng Sun ◽  
...  

Background/Aim.Bax-interacting factor-1 (Bif-1) plays a crucial role in apoptosis and autophagy. The aim of this study was to evaluate Bif-1 protein expression and its prognostic significance in colorectal cancer (CRC).Methods.We analyzed Bif-1 protein expression in 251 resected specimens from patients with CRC by immunohistochemistry using tissue microarray.Results.Low Bif-1 expression was observed in 131 patients (52.2%) and high Bif-1 expression in 120 patients (47.8%). No significant differences were observed in clinicopathological parameters between patients with high and low Bif-1 expression. Kaplan-Meier survival analysis showed no difference in survival between patients with high and low Bif-1 expression. Stratified analysis of Bif-1 according to TNM stage demonstrated that low Bif-1 expression was significantly associated with a poor outcome in patients with stages I and II (P=0.034). Stratified multivariate analysis demonstrated that low Bif-1 expression was an independent indicator of poor prognosis (hazard ratio, 0.459; 95% confidence interval, 0.285–0.739;P=0.001).Conclusion.Patients with low levels of Bif-1 expression have shortened survival rates in CRC of stages I and II. This suggests that Bif-1 protein expression may be a useful prognostic marker in early-stage CRC.


2021 ◽  
Vol 75 (5) ◽  
pp. 1-8
Author(s):  
Jakub Milecki ◽  
Małgorzata Żmijewska-Tomczak ◽  
Krzysztof Osmola ◽  
Małgorzata Wierzbicka

Radiotherapy (RT) for patients with head and neck squamous cell carcinoma (HNSCC) affects vital functions related to the irradiation volume of the head and neck region and, in addition, has a negative impact on social functioning, thereby significantly impairing patients’ quality of life (QoL). The aim of this study was to assess changes in the quality of life in patients with head and neck cancer treated with curative RT at 12 months after completion of RT. The aim of this study was to assess the differences between the baseline QoL of patients with early clinical stage HNSCC and at 12 months after curative/radical RT. The prospective clinical study included 92 patients in good general condition (ECOG 0–1 – Eastern Cooperative Oncology Group performance status), without regional or distant metastases, diagnosed with pathomorphologically confirmed early-stage head and neck squamous cell carcinoma treated with definitive RT. All patients participating in the study signed an informed consent form. QoL was assessed using the standard EORTC QLQ-C30 and QLQH&N35 questionnaires. In addition, information on clinical aspects and data relating to socio-demographic factors were obtained from each patient. Statistical analysis was performed using a statistical package (SPSS 17.0). T-test was used for dependent and independent samples. A general linear model was used for repeated measures. Patients’ QoL deteriorated significantly after definitive RT. Worse QoL Core-30 scores in patients 12 months after the end of RT, compared with baseline QoL, before the start of RT, were observed in domains such as physical performance, fulfillment of life roles, cognitive functioning, loss of appetite, fatigue and constipation. For the QLQ-H&N35 questionnaires, patients 12 months after the end of RT reported problems in relation to aspects of life such as senses, mouth opening, dry mouth, thick saliva, pain, and weight loss. RT, even in early clinical stage head and neck cancer, has a negative impact on QoL, despite modern treatment techniques.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7520-7520 ◽  
Author(s):  
K. Pisters ◽  
E. Vallieres ◽  
P. A. Bunn ◽  
J. Crowley ◽  
K. Chansky ◽  
...  

7520 Background: Small randomized and non-randomized studies suggest induction chemotherapy may improve survival in early stage NSCLC. The primary objective of this study was to determine if induction PC could improve survival over surgery alone. Preliminary results of this trial were reported at ASCO 2005 (J Clin Oncol, ASCO Proc 23(16S) 2005:7012). Median time for patients alive at last contact is now 46 months (mos). Methods: Consenting patients with clinical stage T2N0, T1–2N1 and T3N0–1 NSCLC (excluding superior sulcus tumors) were stratified by clinical stage (IB/IIA vs. IIB/IIIA) and randomized to induction PC (P:225 mg/m2 over 3 hours, C:AUC=6) on day 1, every 3 weeks × 3 or surgery alone. Eligible patients had a performance status 0–1, age =18 years (yrs), predicted post- resection FEV1 =1.0L. Surgery was at least a lobectomy and mediastinal nodal sampling. The primary endpoint was a 33% increase in overall survival over expected 2.7 yrs median for surgery. Planned sample size was 600 patients, 81% power, 1-sided test, 0.025 significance. Results: S9900 closed 07/04 when adjuvant chemotherapy became standard. 354 patients had accrued; 174-surgery alone, 180- induction PC; 19 were ineligible. Median age 65 yrs, 66% male, 70% IB/IIA, 30% IIB/IIIA. Major radiographic response to induction PC was 41%. Treatment-related deaths: 3 during induction PC, 11 within 30 days of surgery (7-induction PC arm, 4-control). Progression-free survival (PFS), overall (OS) survival rates and hazard ratios (HR) are shown. Conclusions: PFS and OS continue to trend in favor of induction PC with HR similar to those observed in adjuvant trials, supporting the role of chemotherapy in operable NSCLC. Randomized trials comparing induction to adjuvant chemotherapy are warranted. Supported by SWOG CA30102. [Table: see text] [Table: see text]


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15111-e15111
Author(s):  
A. Takeda

e15111 Background: Neuropilin (NRP) was initially described as non-tyrosine kinase receptors for neuron guidance factor belonging to the Semaphorin family. Two subtypes, NRP-1 and NRP-2 have been isolated. Neuropilins are widely expressed not only normal developing tissues but also several types of tumor cells. It was reported that the expression of NRP-1 is increased by VEGF, mediated through VEGFR-2, which correlates with tumor growth and invasiveness in colorectal cancer. NRP-2 knockout mice studies showed marked deficits in the development of small lymphatic vessels and its function was associated with the formation of lymphatic network, but the role of NRP-2 in colorectal cancer remains unknown. Methods: We have newly established two useful anti- Neuropilin antibodies against CUB domains of NRP-1 and cytoplasmic domains of NRP-2. In recent study, we have analyzed the expression of NRP-1 and NRP-2 in some cultured cell lines by western blot and the clinicopathological significance in colorectal cancer. Tissues samples were obtained from 72 primary colorectal adenocarcinomas (colon:39 cases, rectum:33 cases). The pathologic stage were as follows; stageI:10 patients, II:25 patients, III:26 patients and IV:11 patients. NRP-1 and NRP-2 gene expression was evaluated by RT- PCR, which was compared with immunohistochemical examination of colorectal cancer tissues. Constitutive expression of NRP-1 was detected in PC3, HT29, PC9 and PC13 cell lines and NRP-2 in HT29, PC3 and PC9. Results: There was significant correlation between NRP-1 and -2 protein expression and both of mRNA expression. The expression of NRP-1 showed apparent correlation with liver metastasis (p=0.027) and venous invasion (p=0.0025), while NRP-2 expression was correlated with lymph node metastasis (0.001) and lymphatic invasion (0.039) by immunohistochemical analysis. The post-surgical treatment observation revealed that patients with co- expression of NRP-1 and NRP-2 were significantly correlated with poorer prognosis than both NRP-1 and NRP-2 negative patients (p=0.035). Conclusions: These results suggest that NRP-1 acts as angiogenesis factor and NRP-2 acts lymphangiogenesis factor, both of them are useful predictive marker in colorectal cancer. No significant financial relationships to disclose.


2011 ◽  
Vol 29 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Ramon Salazar ◽  
Paul Roepman ◽  
Gabriel Capella ◽  
Victor Moreno ◽  
Iris Simon ◽  
...  

Purpose This study aims to develop a robust gene expression classifier that can predict disease relapse in patients with early-stage colorectal cancer (CRC). Patients and Methods Fresh frozen tumor tissue from 188 patients with stage I to IV CRC undergoing surgery was analyzed using Agilent 44K oligonucleotide arrays. Median follow-up time was 65.1 months, and the majority of patients (83.6%) did not receive adjuvant chemotherapy. A nearest mean classifier was developed using a cross-validation procedure to score all genes for their association with 5-year distant metastasis–free survival. Results An optimal set of 18 genes was identified and used to construct a prognostic classifier (ColoPrint). The signature was validated on an independent set of 206 samples from patients with stage I, II, and III CRC. The signature classified 60% of patients as low risk and 40% as high risk. Five-year relapse-free survival rates were 87.6% (95% CI, 81.5% to 93.7%) and 67.2% (95% CI, 55.4% to 79.0%) for low- and high-risk patients, respectively, with a hazard ratio (HR) of 2.5 (95% CI, 1.33 to 4.73; P = .005). In multivariate analysis, the signature remained one of the most significant prognostic factors, with an HR of 2.69 (95% CI, 1.41 to 5.14; P = .003). In patients with stage II CRC, the signature had an HR of 3.34 (P = .017) and was superior to American Society of Clinical Oncology criteria in assessing the risk of cancer recurrence without prescreening for microsatellite instability (MSI). Conclusion ColoPrint significantly improves the prognostic accuracy of pathologic factors and MSI in patients with stage II and III CRC and facilitates the identification of patients with stage II disease who may be safely managed without chemotherapy.


Acta Naturae ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 62-67
Author(s):  
A. R. Kim ◽  
T. A. Pavlenko ◽  
L. A. Katargina ◽  
N. B. Chesnokova ◽  
M. V. Ugrumov

Parkinsons disease (PD) is a systemic neurodegenerative condition caused by the death of dopaminergic neurons of the nigrostriatal system of the brain. This disease is diagnosed after most neurons have already been lost, which explains the low efficiency of treatment. Hope for increasing treatment efficiency rests in the development of new strategies for early diagnosis of PD based on a search for peripheral markers that appear as early changes in non-motor functions. Since impairment of the visual function is one of the manifestations of PD, the purpose of our work was to identify biochemical and physiological changes in a mouses eye and eyelid in models of preclinical (presymptomatic) and clinical (symptomatic) stages of PD. We found that the norepinephrine, dopamine, and serotonin levels in the mouse eye reduced not only in the model of the early clinical stage, but also in the model of preclinical stage, an indication that pathological changes in the monoaminergic systems of the brain had affected the eye even before the motor disorders emerged. Moreover, in both models of PD, mice had increased intraocular pressure, indicating the development of both metabolic and functional impairments, which can be used as diagnostic markers. Unlike in the eye, the serotonin level in the eyelid was increased in mice at both parkinsonism stages and in presymptomatic mice to a much higher extent than in symptomatic ones. Given that serotonin is involved in the regulation of lacrimal glands of the eyelid, an increase in its level in parkinsonian mice should alter the composition of tear fluid, which could serve as a diagnostic marker of early stage of PD. Thus, the changes in the metabolism of monoamines in the eye and eyelid observed in mice at the early stage of parkinsonism are accompanied by changes in the function of these structures and, therefore, can be used as diagnostic markers of the early stage of PD.


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