NOTCH1 as a potential prognostic biomarker for anti-VEGF therapy in patients with metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11038-11038
Author(s):  
Tadeu Ferreira Paiva ◽  
Alexandre Andre Balieiro Anastacio da Costa ◽  
Flavio Augusto Ismael Pinto ◽  
Victor Hugo Fonseca Jesus ◽  
Raul A. Marques ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Lymph Node Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Response Rate ◽  
High Expression ◽  
Node Metastasis

11038 Background: There are no validated biomarkers for clinical response or survival benefit in patients treated with bevacizumab (Bv) in advanced metastatic colorectal cancer (mCRC). The aim of this study was to evaluate the predictive value of putative biomarkers in mCRC. Methods: One hundred and five mCRC patients who received Bv combined with FOLFOX or FOLFIRI were retrospectively evaluated for clinical and pathological characteristics. VEGFR1, VEGFR2, VEGFR3, PlGF, DLL4 and NOTCH1 expression were assessed by immunohistochemistry on formalin-fixed, paraffin-embedded neoplastic tissue of either primary or metastatic tissue in a tissue microarray. High levels of expression were defined as less than or equal to or more than the median. Survival curves were calculated by the Kaplan-Meier method and compared by the log-rank test. For multivariate analysis the Cox proportional hazards model was used. Results: Grade 1 or 2 (p=0.01), non-mucin-producing histology (p=0.04) and presence of liver metastasis (p=0.001) were associated with a higher response rate. There was no difference between the expression of markers and the response rate. ECOG 0 or 1 (p=0.002), grade 1 or 2 (p=0.02), liver metastasis (p=0.003), no lymph node metastasis (p=0.01) no peritoneal metastasis (p=0.02) and resection of metastasis (p<0.001) were correlated with higher progression-free survival (PFS). There was also a strong correlation between ECOG 0 or 1 (p=0.001), grade 1 or 2 (p=0.006), no lymph node metastasis (p=0.004), liver metastasis (p<0.001) and resection of metastasis (p<0.0001) with better overall survival. There was a trend between high expression of NOTCH1 (p=0.06) and worst PFS.High expression of VEGFR2 (p=0.07) was slightly associated with a better overall survival, while high expression of NOTCH1 was associated with a worse overall survival (p=0.01). Using multivariate analysis, NOTCH1 proved to be an independent variable for adverse overall survival (HR 2.01, IC 1.07 – 3.77, p=0.02). Conclusions: High NOTCH1 expression assessed by immunohistochemistry is capable of predicting poor survival in advanced colorectal cancer patients treated with bevacizumab.

CD133 status influences in prognosis of patients with metastatic colorectal cancer receiving cetuximab.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 509-509 ◽  
Author(s):  
Dai Inoue ◽  
Satoshi Matsusaka ◽  
Noriko Yamamoto ◽  
Mitsukuni Suenaga ◽  
Yuji Mishima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Lymph Node Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Lung Metastasis ◽  
Peritoneal Metastasis ◽  
Chimeric Mouse ◽  
Cox Regression Analysis ◽  
Node Metastasis

509 Background: Recently, the cancer stem cell (CSC) theory has been proposed, and CD133 has been suggested as a potential marker of CSCs in metastatic colorectal cancer (mCRC). Cetuximab, an IgG1 anti-EGFR chimeric mouse/human monoclonal antibody, has been approved for the treatment of mCRC. The purpose of this study is to evaluate the prognostic significance of CD133 expression in mCRC treated with cetuximab in combination with chemotherapy. Methods: We evaluated the prognosis of pts with mCRC treated with cetuximab retrospectively, and performed immunohistochemical staining to analyze the CD133 status. Non-parametric statistics, univariate and multivariate analysis were used. Results: From October 2008 to June 2009, 56 pts with measurable metastatic colorectal cancer were received cetuximab and 43 were evaluable. Patients characteristics were as follows : median age : 59.6 years (range 28-80) , PS 0/1 : 30/13 , colon/rectum : 28/15 , metastatic site (liver +/- : 35/8 , lung +/- : 32/11 , bone +/- : 6/37 , peritoneum +/- : 6/37 , lymph node +/- : 11/32 , local +/- : 3/40), best response rate was 9.3% (CR/PR/SD/PD : 1/3/19/11). Compared with CD133- pts with colorectal cancer , the progression-free survival (PFS) of CD133+ pts was significantly better (5.5 month; 95% CI, 4.4-6.7,p=0.026), and median overall survival (OS) was also significantly better (11.0 month; 95% CI, 5.4-16.5, p=0.002). In univariate analysis, liver metastasis, lung metastasis, peritoneal metastasis, lymph node metastasis, age, and CD133 at the baseline predicted PFS, and age, gender, liver metastasis, lung metastasis, bone metastasis, peritoneal metastasis, lymph node metastasis at the baseline, the presence of skin rash, and CD133 predicted OS. In order to evaluate the independent predictive effect of chemotherapy, multivariate Cox regression analysis was carried out. It showed that CD133 was the strongest predictor. Conclusions: CD133 status at the baseline was correlated with the prognosis of patients treated with cetuximab, suggesting that CD133 status might play a role to estimate the prognosis.

Fraction of LOH on chromosome 17 and 18 (LOH-ratio) predicts colorectal cancer outcome

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20114-20114
Author(s):  
T. Kanazawa ◽  
T. Watanabe ◽  
H. Nagawa
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Chromosome 17 ◽  
Rank Statistic ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Node Metastasis ◽  
Predictors Of Recurrence

20114 Background: Identification of patients at high risk for recurrence remains a central issue in the treatment of colorectal cancer. Our goal was to identify predictive factors for recurrence in colorectal cancer patients. Methods: DNA from 84 colorectal cancers were analyzed for wide-ranging allelotyping. Using 27 microsatellite markers spanning every 10cM on chromosome 17 and 18, we defined the LOH-ratio as the proportion of markers which show LOH out of 27 markers. Tumors were grouped into two groups by the median value of LOH-ratio (0.19). Recurrence free survival was compared with Kaplan-Meier analysis and log rank statistic. The Cox proportional hazards regression model was used for both univariate and multivariate analysis of recurrence free survival. Results: Log rank statistic revealed that LOH-ratio, stage, lymph node metastasis significantly related to recurrence free survival. On univariate analysis, significant predictors of Recurrence free survival were LOH-ratio, lymph node metastasis, Dukes’ classification, and pathological type. On multivariate analysis, LOH-ratio (HR 3.1, p = 0.02) and lymph node metastasis (HR 5.2, p = 0.002) independently predicted for recurrence free survival. Conclusions: LOH-ratio and lymph node metastasis were the only independent predictors of recurrence free survival. Altogether with lymph node metastasis, LOH-ratio could help to improve postoperative surveillance and adjuvant therapy. No significant financial relationships to disclose.

The expression of THOX2 in colorectal mucinous adenocarcinoma and its relationship with prognosis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15529-e15529
Author(s):  
Xue Zhang ◽  
Jing Han ◽  
Zhisong Fan ◽  
Li Feng ◽  
Long Wang ◽  
...  
Keyword(s):  
Lymph Node ◽  
Liver Metastasis ◽  
Lymph Node Metastasis ◽  
Peritoneal Metastasis ◽  
Mucinous Adenocarcinoma ◽  
High Expression ◽  
Clinicopathological Parameters ◽  
Node Metastasis ◽  
Potential Biomarker ◽  
Colorectal Mucinous Adenocarcinoma

e15529 Background: The role of THOX2 in the occurrence and development of tumors has gradually attracted attention, but there is no study on the expression and function of THOX2 in colorectal mucinous adenocarcinoma (MC). The purpose of this study was to investigate the expression of thyroid oxidase 2 (THOX2) in colorectal MC and its relationship with prognosis. Methods: 30 patients with colorectal adenocarcinoma (AC) and 15 patients with MC were selected from The Fourth hospital of Hebei Medical University from October 1, 2018 to July 1, 2019. They were selected to detect the mRNA and protein levels of THOX2 in the colorectal cancer tissues of the two different pathological types using qRT-PCR and immunohistochemistry (IHC) methods. A total of 109 patients with MC who received surgical treatment between January 1, 2015 and January 1, 2015 were selected. The clinicopathological parameters of the patients were collected and survival follow-up was performed. The expression of THOX2 protein in MC tissues was detected by IHC test, and the differences in the expression of THOX2 protein in different tissues were analyzed by χ2 test. Cox univariate and multivariate analyses were used to investigate the relationship between clinicopathological characteristics, THOX2 protein expression level and DFS and OS in patients with MC. Results: The levels of THOX2 mRNA and protein in 15 cases of MC were significantly higher than those in 30 cases of AC. The high expression of THOX2 protein in MC tissues was closely correlated with tumor site, whether mixed with other pathological types, TNM stage, lymph node metastasis, M stage, and liver metastasis, peritoneal metastasis and other site metastasis occurred in patients after initial treatment. Cox regression analysis of 95 patients' survival data showed that high expression of THOX2, right colon and lymph node metastasis were influential factors for DFS in MC patients, and were independent prognostic factors for predicting DFS in MC patients. The expression of THOX2, lymph node metastasis, liver metastasis after adjuvant therapy and peritoneal metastasis are the influencing factors of OS in MC patients. Lymph node metastasis is an independent prognostic factor for OS in MC patients. Conclusions: The expression of THOX2 in MC was significantly higher than that of AC, and it was related to the malignant biological manifestations of tumor. At the same time, the high expression of THOX2 is associated with short DFS and OS in patients with MC, and may be used as a potential biomarker and efficacy predictor for MC patients.

scholarly journals Long non-coding RNA XIST expression as a prognostic factor in human cancers: A meta-analysis

2019 ◽  
Vol 34 (4) ◽  
pp. 327-333
Author(s):  
Shuai Yin ◽  
Jiayu Dou ◽  
Guifang Yang ◽  
Fangfang Chen
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Patients ◽  
Distant Metastasis ◽  
Poor Prognosis ◽  
Meta Analysis ◽  
High Expression ◽  
Xist Expression ◽  
Node Metastasis

A large number of literature has shown that high expression of X inactive-specific transcript (XIST) is associated with poor prognosis and metastasis of cancer in patients. However, most of this literature is limited by the small sample sizes and discrete outcomes. Therefore, a meta-analysis was performed to investigate the relation between XIST expression and tumor node metastasis (TNM) stage, lymph node metastasis, distant metastasis, and overall survival of cancer patients. We searched for literature in PubMed, Embase, and Web of Science. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association of XIST expression with prognosis and clinicopathological characteristics of cancer patients. Finally, a total of 14 articles involving 1123 patients were included in this meta-analysis. The results suggested that high expression of XIST has a significant relationship with a relatively poor overall survival for patients with malignant tumors (HR 1.82; 95% CI 1.32, 2.52; P = 0.0003). Moreover, high expression of XIST was significantly associated with poor TNM stage (OR 3.64; 95% CI 2.62, 5.07; P < 0.0001), lymph node metastasis (OR 2.39; 95% CI 1.65, 3.46; P < 0.0001) and distant metastasis (OR 2.84; 95% CI 1.90, 4.23; P < 0.0001). In conclusion, high expression of lncRNA XIST may be a predictive factor of poor prognosis in human cancers.

26 ctDNA clearance and radiographic resolution of lymph node metastasis in a patient with metastatic microsatellite stable colorectal cancer on immunotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A25-A25
Author(s):  
Charles Schneider ◽  
Michael Krainock ◽  
Meenakshi Malhotra ◽  
Paul Billings ◽  
Alexey Aleshin
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Microsatellite Instability ◽  
Metastatic Colorectal Cancer ◽  
Mismatch Repair ◽  
Node Metastasis ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Time Point

BackgroundHigh microsatellite instability (MSI-H) in metastatic colorectal cancer (mCRC) is associated with a beneficial response to immunotherapy. Additionally, within MSI-H cancers, tumor mutational burden (TMB) is independently predictive of immunotherapy responsiveness.1 Durable responses to therapy have been demonstrated in patients with MSI-H mCRC treated with Nivolumab and Ipilimumab.2 However, less is known about treatment responsiveness in patients with high mutational burden mCRC that demonstrates microsatellite stability (MSI-L).MethodsWe report on a 55-year-old female with a PALB-2 germline mutation who presented with a right-sided colonic adenocarcinoma with the involvement of the omentum and liver. The patient received 6 cycles of neoadjuvant FOLFOX, followed by an extended right hemicolectomy, omentectomy, and partial liver resection. The surgical specimen revealed a moderately differentiated adenocarcinoma in the cecum demonstrating a poor response to chemotherapy, 0/23 lymph nodes positive, one focus of adenocarcinoma in the liver with clear margins, and focal omental involvement with adenocarcinoma. The patient subsequently underwent 6 cycles of ‘adjuvant’ FOLFOX, with Oxaliplatin omitted after 3 cycles secondary to peripheral neuropathy. Soon after the patient experienced a recurrence that involved the anterior abdominal wall, between the peritoneum, and stomach, which was subsequently resected with negative margins. Molecular profiling of this metastatic focus revealed a TMB of 15.4 mutations per megabase, proficient Mismatch Repair (pMMR), a PDL1 CPS score of 26, and microsatellite stable (MSS) status. First, ctDNA analysis was performed at the time of recurrence and was found to be positive. Based on the TMB score of 15.4 and an elevated PDL1 score, the patient was initiated on Nivolumab and Ipilimumab. ctDNA measurements were obtained at the patient‘s request.ResultsDNA assessment performed after surgery and prior to initiation of immunotherapy revealed an approximate doubling of ctDNA levels, measured in mean tumor molecules (MTM) per mL of plasma, every month. During this period of time and correlating with the rise in ctDNA levels, the patient developed a new and enlarging FDG avid cardiophrenic lymph node. Following 2 cycles of Nivolumab and Ipilimumab, the FDG avid lymph node completely resolved and ctDNA clearance was observed (figure 1).Abstract 26 Figure 1ctDNA time-course demonstrating ctDNA kineticsTime-point A represents the initial ctDNA assay, performed at the time of resection of peritoneal metastasis. An additional time-point (B) drawn a month later reveals a further increase in ctDNA. Time-point C represents a peak in ctDNA levels, concomitant with the new emergence of a PET avid cardiophrenic lymph node. Combination Immunotherapy (IO) was begun shortly after time-point C. Time-point D represents ctDNA clearance and radiographic resolution of lymph node metastasis after two cycles of IO. MTM/mL - mean tumor molecules/milliliter of plasmaConclusionsHere we present a case of ctDNA clearance correlating with a radiographic resolution of metastatic disease in a patient with MSS mCRC. The data is provocative and suggests a possible contributory role of ctDNA-based testing as an additional monitoring parameter to measure disease-responsiveness to immunotherapy. Further investigation is warranted.Ethics ApprovalN/AConsentN/AReferencesSchrock AB, Ouyang C, Sandhu J, Sokol E, Jin D, Ross J8, Miller VA, Lim D, Amanam l, Chao J, Catenacci D, Cho M, Braiteh 7, Klempner SJ, Ali 8M, Fakih M. Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSl-high metastatic colorectal cancer. Ann Oncol 2019;30(7):1096–1103Overman MJ, et al. Durable Clinical/Benefit With Nivolumab Plus lpilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. Clin Oncol 2018;36(8):773–779.

Expression and prognostic significance of ECT2 in invasive breast cancer

2017 ◽  
Vol 71 (5) ◽  
pp. 442-445 ◽  
Author(s):  
Hong-kun Wang ◽  
Jian-fang Liang ◽  
Hui-xia Zheng ◽  
Hong Xiao
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Triple Negative ◽  
Prognostic Significance ◽  
High Expression ◽  
Proliferation Index ◽  
Ki 67 ◽  
Node Metastasis

AimsTo investigate the expression of epithelial cell transforming sequence 2 (ECT2) in invasive breast cancer and its prognostic significance.MethodsECT2 immunohistochemical detection was performed in 165 breast cancer specimens and 100 normal control tissues. Univariable and multivariable Cox proportional hazards regression model analysis was used to confirm independent prognostic factors. The PHREG procedure linear hypotheses testing method was used to analyse survival data.ResultsExpression of ECT2 in breast cancer was significantly higher than that of the normal control group (p<0.001), and it was related to tumour grade, the status of lymph node metastasis, TNM staging, recurrence status, menopausal status, and the Ki-67 proliferation index (p<0.05), and not related to age, tumour size, tumour type, expression of estrogen receptor, progesterone receptor and human epidermal growth factor 2, and triple-negative disease (p>0.05). Univariable analysis showed that expression of ECT2, the status of lymph node metastasis, triple-negative disease and Ki-67 proliferation index were related to the overall survival of patients with breast cancer (p<0.001, p=0.006, p=0.001, p=0.041, respectively). PHREG procedure linear hypotheses testing results for overall survival revealed that high expression of ECT2, lymph node metastasis, triple-negative disease and high Ki-67 proliferation index predicted lower overall survival rates. Multivariable Cox regression indicated that high expression of ECT2 and triple-negative disease were independent prognostic factors for patients with breast cancer (p<0.001, p=0.004, respectively).ConclusionsExpression of ECT2 may be one of the main causes of the occurrence and development of breast cancer, and high expression of ECT2 as an independent prognostic factor predicts a poor prognosis. ECT2 could also be a potential molecular target for designing therapeutic strategies for breast cancer.

scholarly journals Prognostic Prediction Models for Liver Metastasis and Overall Survival in Colorectal Cancer Patients

2021 ◽  
Vol 105 (1-3) ◽  
pp. 442-448
Author(s):  
Norikatsu Miyoshi ◽  
Masayuki Ohue ◽  
Masayoshi Yasui ◽  
Yusuke Takahashi ◽  
Shiki Fujino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Tumor Invasion ◽  
Prediction Models ◽  
Venous Invasion ◽  
Node Metastasis ◽  
Preoperative Serum ◽  
Clinicopathologic Factors

Objective The objective of this study was to develop novel prediction models for liver metastasis-free survival (LMFS) and overall survival (OS) in colorectal cancer (CRC) patients following surgically curative resections. We developed novel prediction models for LMFS and OS in CRC patients following surgically curative resections. Using clinicopathologic factors, such models were constructed with concordance indices of 0.811 and 0.776 for LMFS and OS, respectively. Methods Seven hundred seventy-six CRC patients presenting to the Osaka Medical Center for Cancer and Cardiovascular Diseases between January 2004 and December 2010 were retrospectively studied. The exclusion criteria were patients with preoperative treatment, synchronous distant metastasis, noncurative resection, and incomplete postoperative follow-up. Results Based on the analysis of clinicopathologic factors, the following factors had significant correlation with LMFS: preoperative serum carcinoembryonic antigen (pre-CEA), tumor invasion, lymph node metastasis, lymphatic invasion, and venous invasion. Using these variables, a novel prediction model was constructed by the Cox regression model with a concordance index (c-index) of 0.811 for LMFS. The following factors had a significant correlation with OS: age, pre-CEA, preoperative serum carbohydrate antigen 19-9, tumor location, pathologically defined tumor invasion, lymph node metastasis, and venous invasion. Using these variables, a prediction model was constructed with a c-index of 0.776 for OS. These models were validated by external datasets in an independent patient group. Conclusions We demonstrated the utility of a novel personalized prognostic model for liver metastasis, integrating tumor node metastasis factors, pre-CEA, and histologic lymphovascular invasion to predict the prognosis. Such models can help clinicians in treating CRC patients postoperatively.

scholarly journals High expression of ADAMTS5 is a potent marker for lymphatic invasion and lymph node metastasis in colorectal cancer

2016 ◽  
Vol 6 (1) ◽  
pp. 130-134 ◽  
Author(s):  
Naotsugu Haraguchi ◽  
Nobuyoshi Ohara ◽  
Jun Koseki ◽  
Hidekazu Takahashi ◽  
Junichi Nishimura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymphatic Invasion ◽  
High Expression ◽  
Node Metastasis
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