ZEB1 expression in different stages of colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15526-e15526
Author(s):  
Evgeniya M. Nepomnyashchaya ◽  
Elena P. Ulianova ◽  
Inna A. Novikova ◽  
Aleksandr B. Sagakyants ◽  
Maksim N. Chernyak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Progression ◽  
Nuclear Reaction ◽  
Statistical Significance ◽  
Stage Iv ◽  
Stage Ii ◽  
Stage Iii ◽  
Positive Staining ◽  
Mesenchymal Transition ◽  
Zeb1 Expression

e15526 Background: Colorectal cancer (CRC) is among the most common cancers. The leading cause of high mortality is tumor progression developed due to the epithelial to mesenchymal transition (EMT). The ZEB1 protein is one of the critical regulators of this process. In this regard, our study aimed to assess the ZEB1 expression in different stages of colorectal cancer. Methods: This study included samples of 206 patients with stage II-IV CRC aged 42 to 86 years (mean age 64.2±1.7). All patients were divided into three groups: group 1 - patients with T3-4 N0 M0 (stage II) with high-risk factors for recurrence, n = 6; group 2 - patients with T1-4 N1-2 M0 (stage III), n = 88; group 3 - patients with T1-4 N0-2 M1 (stage IV), n = 58. IHC study was performed using polyclonal rabbit antibodies to ZEB1 (Biorbyt Ltd.) diluted 1:200 and a Reveal Polyvalent HRP-DAB Detection System. The staining percentage and intensity were assessed: 0, 1+ weak, 2+ moderate, 3+ strong. The nuclear reaction of the ZEB1 protein was considered positive when staining was detected in more than 10% (cut-off) of tumor cells with intensities of 2+ and 3+. Statistical analysis of the results was carried out using the STATISTICA 13.0 software (StatSoft Inc., USA). Results: A positive nuclear reaction for ZEB1 was detected in 80.6% (166 of 206 patients), while negative in 19.4% (40 of 206 patients). The maximal percentage of patients with positive staining for ZEB1 was among those with stage IV (94.8%), the minimal percentage - stage II (60%). The prevalence of ZEB1+ in patients with stages III and IV significantly increased the risk of tumor progression by 3.5 (95% CI 1.8-8.4) and 12.2 (95% CI 3.4-43.6) times, respectively, compared with stage II patients. No statistical significance was observed in the comparison between patients with stages III and IV (95% CI 0.9-11.7). The percentage of ZEB1+ samples increased in more advanced tumors. The ratio of ZEB1+/ZEB1- tumors in stage II was 1.5, in stage III - 5.8, in stage IV - 18.3 (p < 0.05). Conclusions: The immunohistochemical study revealed the features of ZEB1 expression in different stages of colorectal cancer, which can serve as prognostic factors that determine the disease progression.

Serum-based multiplex protein assay for early detection of colorectal cancer and precancerous lesions in a FIT positive population.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16145-e16145
Author(s):  
Herbert A. Fritsche ◽  
Jason Lee Liggett ◽  
Hong Zhang ◽  
Linnea Ferm ◽  
Ib Jarle Christensen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Stage Iv ◽  
Stage I ◽  
Stage Ii ◽  
Supervised Machine Learning ◽  
Stage Iii ◽  
Screening Programs ◽  
Medium Risk ◽  
Validation Set

e16145 Background: Colorectal cancer (CRC) is the second leading cancer worldwide in terms of incidence, 5-year prevalence and mortality for both women and men ages 45 years old and up. The current screening method for many countries with organized screening programs is the FIT test for fecal occult blood; however, this test can result in false positive rates as high as 65%. A FIT reflex test could reduce unnecessary colonoscopies while reducing wait times for those patients that need confirmatory colonoscopies the most. Methods: Danish FIT positive colonoscopy confirmed serum samples (n = 1,499) were divided into training and validation sets maintaining approximately equivalent percentages of clean colonoscopy (40%), low risk adenomas (16%), medium risk adenomas (19%), high risk adenomas (13%), stage I CRC (5%), stage II CRC (2%), stage III CRC (4%), and stage IV CRC (0.5%). Proteins were quantified by custom 16-plex immunoassays utilizing the Luminex xMAP platform. A support vector machine supervised machine learning algorithm was trained with the 16 biomarkers plus age and FIT concentration using 1,291 samples for the outcome medium risk adenoma, high risk adenoma, and CRC. Then this algorithm was tested on a blind 208 sample validation set. Results: The training set was 90% sensitive and 27% specific (AUC = 0.68) and the validation set was 93% sensitive and 21% specific (AUC = 0.63). The sensitivities of the validation by risk/stage was as follows: medium risk adenoma 91%, high risk adenomas 92%, stage I CRC 100%, stage II CRC 100%, stage III CRC 100%, stage IV CRC 93%. Conclusions: This study demonstrates feasibility of a novel blood-based multiplex protein immunoassay for use as a reflex to FIT positive results in population wide screening. It detected nearly all adenomas and carcinomas while reducing FIT false positives and thus unnecessary colonoscopies by more than 20%. A FIT reflex test could alleviate endoscopy burden experienced in countries with organized cancer screening programs, while providing better patient outcomes by detecting polyps and early-stage CRC with high sensitivity.

scholarly journals Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 180 ◽  
Author(s):  
Tianhua Guo ◽  
Marcin Krzystanek ◽  
Zoltan Szallasi ◽  
Arpad Szallasi
Keyword(s):  
Colorectal Cancer ◽  
Platelet Count ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Stage Iv ◽  
Early Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Normal Limits ◽  
Stage Ii Colon Cancer

Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 × 103/μl) in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our Institution between 2004 and 2013. The patients (48.7% male and 51.3% female) had a mean age of 69.9 years (+/- 12.7 years) at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients). Although the mean platelet count increased with the depth of tumor invasion (pT), its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57) had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4%) with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery). The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis may be considered for adjuvant chemotherapy.

scholarly journals Treatment and Outcomes of Colorectal Cancer in Armenia: A Real-World Experience From a Developing Country

2020 ◽  
pp. 1286-1297
Author(s):  
Samvel Bardakhchyan ◽  
Sergo Mkhitaryan ◽  
Davit Zohrabyan ◽  
Liana Safaryan ◽  
Armen Avagyan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Survival Rates ◽  
Stage Iv ◽  
Final Analysis ◽  
Stage Ii ◽  
Stage Iii ◽  
Rank Test

PURPOSE In Armenia, colorectal cancer (CRC) is one of the most frequently diagnosed cancers. It is in the third place by incidence. The aim of this study was to evaluate treatment and outcomes of CRC in Armenia during the last 9 years. MATERIALS AND METHODS For this retrospective hospital-based study, we have collected data from two main oncology centers in Armenia: National Oncology Center and “Muratsan” Hospital of Yerevan State Medical University. The information about patients with CRC who were treated at these two centers between January 1, 2010 and July 1, 2018 was collected from the medical records. Log-rank test and Kaplan-Meier curves were used for survival analysis. Prognostic factors were identified by Cox regression. RESULTS A total of 602 patients with CRC were involved in the final analysis. Median follow-up time was 37 months (range, 3-207 months). A total of 8.6% of patients had stage I, 32.9% stage II, 38.0% stage III, and 17.6% stage IV cancer; for 2.7% patients, the stage was unknown. The main independent prognostic factors for overall survival (OS) were tumor stage, grade, and histology. Adjuvant chemotherapy has been shown to improve survival in stage II colon cancer and stage III rectal but not in stage II rectal cancer. Radiotherapy did not yield survival improvement in stage II or III rectal cancer. Three- and 5-year OS rates were 62.9% and 51.8% for all stages combined and 79.7% and 68.5% for stages I-II, 62.5% and 48.4% for stage III, and 24.4% and 17% for stage IV respectively. CONCLUSION As seen from our results, our survival rates are lower than those of the developed world. Additional research is needed to identify the underlying reasons and to improve patients’ treatment and outcomes in Armenia.

Molecular staging with CM10 ProteinChip and SELDI-MS-TOF for colorectal cancer patients before surgery

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3612-3612
Author(s):  
Y. Chen ◽  
W. Xu ◽  
S. Zheng ◽  
S. Zhang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Tumor Staging ◽  
Stage Iv ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Support Vector ◽  
Colorectal Cancer Patients ◽  
Tof Ms

3612 Background: The objectives of this are to detect the serum proteomic patterns by using SELDI-TOF-MS technology and CM10 ProteinChip in colorectal cancer (CRC) patients, and to evaluate the significance of the proteomic patterns in the tumor staging of colorectal cancer. Methods: SELDI-TOF-MS and CM10 ProteinChip were used to detect the serum proteomic patterns of 76 colorectal cancer patients which including 10 Stage I, 19 Stage II, 16 Stage III and 31 Stage IV patients. Models for various stages were developed and validated by using Support Vector Machine, Discriminant Analysis and time-series analysis methods. Results: The first model, formed by 6 protein peaks (M/Z: 2759.58, 2964.66, 2048.01, 4795.90, 4139.77 and 37761.60 Da), could be used to distinguish local CRC patients (StageIand Stage II) from regional CRC patients (Stage III) with an accuracy of 86.67% (39/45). The second model, formed by 3 protein peaks (M/Z: 6885.30, 2058.32 and 8567.75 Da), could be used to distinguish locoregional CRC patients (Stage I,Stage II and Stage III) from systematic CRC patients (Stage IV) with an accuracy of 75.00% (57/76). The third model could distinguish Stage I from Stage II with an accuracy of 86.21% (25/29). The fourth model could distinguish Stage I from Stage III with an accuracy of 84.62% (22/26). The fifth model could distinguish Stage II from Stage III with an accuracy of 85.71% (30/35). The sixth model could distinguish Stage II from Stage IV with an accuracy of 80.00% (40/50). The seventh model could distinguish Stage III from Stage IV with an accuracy of 78.72% (37/47). All four stages could be distinguished by using a two-dimensional scattered spots figure. Conclusion: We conclude that this method is promising in the staging of colorectal cancer patients before surgery. No significant financial relationships to disclose.

scholarly journals Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 180 ◽  
Author(s):  
Tianhua Guo ◽  
Marcin Krzystanek ◽  
Zoltan Szallasi ◽  
Arpad Szallasi
Keyword(s):  
Colorectal Cancer ◽  
Platelet Count ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Stage Iv ◽  
Early Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Normal Limits ◽  
Stage Ii Colon Cancer

Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 K/μl) in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our institution between 2004 and 2013. The patients (48.7% male and 51.3% female) had a mean age of 69.9 years (+/- 12.7 years) at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients). Although the mean platelet count increased with the depth of tumor invasion (pT), its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57) had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4%) with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery). The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis should be upstaged and treated as stage III/IV disease patients.

scholarly journals Expression of epithelial-mesenchymal transition markers E-cadherin and ZEB1 in colorectal cancer

2021 ◽  
Vol 8 (2) ◽  
pp. 23-33
Author(s):  
I. A. Novikova ◽  
O. I. Kit
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Stage Iv ◽  
Stage Ii ◽  
Mean Values ◽  
Mesenchymal Transition ◽  
Number Of Patients ◽  
The Mean ◽  
E Cadherin

Purpose of the study. Evaluation of expression of the epithelial-mesenchymal transition markers E-cadherin and ZEB1 in patients with stage II-IV colorectal cancer (CRC).Materials and methods. The study included operational material obtained from 299 patients aged 42–86 years (mean age 64.2±1.7 years) with stage II-IV CRC treated at National Medical Research Centre for Oncology in 2013-2017. Stage II CRC (T3-4 N0 M0 ) was diagnosed in 110 patients, stage III (T1-4 N1-2 M0 ) – in 88 patients, stage IV (T1-4 N0-2 M1 ) – in 101 patients. Polyclonal rabbit antibodies to ZEB1 (Biorbyt Ltd., UK) and mouse monoclonal antibodies to E-cadherin (Diagnostic BioSystems, USA) were used for an IHC analysis. The intensity and degree of tumor cell staining, percentage of stained tumor cells in the sample and the number of patients with positive and negative marker expression were determined. Groups were compared using the Mann–Whitney U test and the Pearson's chi-square test.Results. Positive expression of E-cadherin was found in 64.5 % (193 of 299 patients), ZEB1 – in 80.6 % (241 of 299 patients). The number of patients with E-cadherin-positive tumors statistically significantly decreased (χ2 =15.888 at p<0.001) from stage II to stage IV, while for ZEB1, on the contrary, it statistically significantly increased (χ2 =43.912 at p><0.001) from stage II to stage IV. The mean values of expression in positively stained cells were: in stage II – E-cadherin 55.3±6.8 %, ZEB1 43.0±5.9 %; in stage III – E-cadherin 38.4±5.8 %, ZEB1 77.0±5.5 %; in stage IV – E-cadherin 14.7±4.7 %, ZEB1 76.9±3.5 %. Significant differences were observed between the mean values of ZEB1 expression in stages III and IV compared to stage II, as well as between the mean values of E-cadherin expression in stages II and III compared to stage IV (p><0.05). No significant differences were found in the mean values of ZEB1 and E-cadherin expression in stages III and IV, II and III respectively.Conclusions. The study demonstrated statistically significant relationship between tumor stages and expression of E-cadherin and ZEB1 in the epithelial-mesenchymal transition. The loss of the E-cadherin expression in tumor cells of patients from stage II to stage IV and increased expression of ZEB1 in the studied groups were statistically significant (p<0.05).

INVESTIGATION KRAS MUTATION IN CIRCULATION TUMOR DNA IN DIFFERENT STAGES OF COLORECTAL CANCER

2019 ◽  
Vol 65 (5) ◽  
pp. 701-707
Author(s):  
Vitaliy Shubin ◽  
Yuriy Shelygin ◽  
Sergey Achkasov ◽  
Yevgeniy Rybakov ◽  
Aleksey Ponomarenko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Plasma Volume ◽  
Kras Mutation ◽  
Stage Iv ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Kras Gene ◽  
Kras Mutations ◽  
Droplet Pcr ◽  
Tumor Dna

To determine mutations in the plasma KRAS gene in patients with colorectal cancer was the aim of this study. The material was obtained from 44 patients with colorectal cancer of different stages (T1-4N0-2bM0-1c). Plasma for the presence of KRAS gene mutation in circulating tumor DNA was investigated using digital droplet polymerase chain reaction (PCR). KRAS mutations in circulating tumor DNA isolated from 1 ml of plasma were detected in 13 (30%) patients with cancer of different stages. Of these, with stage II, there were 3 patients, with III - 5 and with IV - 5. Patients who did not have mutations in 1 ml of plasma were analyzed for mutations of KRAS in circulating tumor DNA isolated from 3 ml of plasma. Five more patients with KRAS mutations were found with II and III stages. The highest concentrations of circulating tumor DNA with KRAS mutation were found in patients with stage IV. The increase in plasma volume to 3 ml did not lead to the identification of mutations in I stage. This study showed that digital droplet PCR allows identification of circulating tumor DNA with the KRAS mutations in patients with stage II-IV of colon cancer. The results can be used to determine the degree of aggressiveness of the tumor at different stages of the disease, but not the 1st, and it is recommended to use a plasma volume of at least 3 ml.

The efficacy of adjuvant chemotherapy for resected high-risk stage II and stage III colorectal cancer in frail patients

2021 ◽  
Author(s):  
Kosuke Mima ◽  
Nobutomo Miyanari ◽  
Keisuke Kosumi ◽  
Takuya Tajiri ◽  
Kosuke Kanemitsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Stage Iii ◽  
Frail Patients

Carboplatin and chlorambucil combination chemotherapy as treatment for patients with ovarian cancer

1994 ◽  
Vol 4 (1) ◽  
pp. 66-71
Author(s):  
B. D. Evans ◽  
P. Chapman ◽  
P. Dady ◽  
G. Forgeson ◽  
D. Perez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Small Volume ◽  
Residual Disease ◽  
Stage Iv ◽  
Complete Response ◽  
Stage Ii ◽  
Stage Iii ◽  
Actuarial Survival ◽  
Moderate Volume ◽  
Grade Iii

Fifty-six patients with ovarian cancer (three stage IC, nine stage II, 33 stage III and II stage IV) were treated with carboplatin 350 mg m−2 i.v. day 1 and chlorambucil orally 0.15 mg kgm−1 days 1–7 inclusive, repeated every 28 days for eight courses. The regimen was well tolerated and was virtually free of nephro- and neurotoxicity. Grade III or IV hematology toxicity occurred in 18 patients but only 31 or 330 courses administered were delayed. Of 40 assessable patients eight achieved a clinical/radiologic complete response and 17 a clinical/radiologic partial response. Actuarial survival at 50 months was 65% for stage II patients, 27% for stage III patients and no stage IV patients survived beyond 20 months. Forty-two per cent of patients with residual disease less 2 cm survived 50 months, compared with 44% of patients with moderate volume (2–5 cm) residual disease and 6% of patients with bulk residual disease. This is an active, well tolerated regimen. However, only patients with small volume residual disease have a significant chance of prolonged survival.

scholarly journals The gravireceptor of Phycomyces. Its development following gravity exposure.

1984 ◽  
Vol 84 (6) ◽  
pp. 845-859 ◽  
Author(s):  
D S Dennison ◽  
W Shropshire
Keyword(s):  
Spatial Relationship ◽  
Stage Iv ◽  
Development Stage ◽  
Stage Ii ◽  
Stage Iii ◽  
Mature Stage ◽  
Early Exposure ◽  
Altered Gravity

The gravitropism of a mature stage IV Phycomyces sporangiophore has a shorter and more uniform latency if the sporangiophore is exposed horizontally to gravity during its earlier development (stage II and stage III). This early exposure to an altered gravitational orientation causes the sporangiophore to develop a gravireceptor as it matures to stage IV and resumes elongation. A technique has been developed to observe the spatial relationship between the vacuole and the protoplasm of a living sporangiophore and to show the reorganization caused by this exposure to altered gravity. Possible gravireceptor mechanisms are discussed.

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