Clinical Significance of Disseminated Pluripotent Tumor Cell SignatureExpression in the Bone Marrow from Patients with Colorectal Cancer

BackgroundMesenchymal stem cells (MSCs) treatment showed promising results in inflammatory bowel disease in both rodent models and patients. Nevertheless, previous studies conducted conflicting results on preclinical tumor models treated with MSCs concerning their influence on tumor initiation and progression. This study is designed to demonstrate the role of bone marrow-derived MSCs and the potential mechanism in the colitis-associated colon cancer (CAC) model.MethodsBone marrow-derived MSCs were isolated from green fluorescent protein-transgenic mice, cultured, and identified by flow cytometry. Azoxymethane and dextran sulfate sodium were administrated to establish the CAC mouse model, and MSCs were infused intraperitoneally once per week. The mice were weighed weekly, and colon length, tumor number, and average tumor size were assessed after the mice were killed. MSC localization was detected by immunofluorescence staining; tumor cell proliferation and apoptosis were measured by immunohistochemistry staining of Ki-67 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay, respectively. The colonic tumor tissues were isolated for RNA-seq, and fecal samples were collected for 16S ribosomal RNA sequencing of the microbiome.ResultsAfter injection intraperitoneally, MSCs migrated to the intestine and inhibited the initiation of colitis-associated colorectal cancer. This inhibition effect was marked by less weight loss, longer colon length, and reduced tumor numbers. Moreover, MSCs reduced tumor cell proliferation and induced tumor cell apoptosis. Furthermore, MSCs could inhibit chronic inflammation assessed by RNA-sequencing and promote gut microbiome normalization detected by 16S ribosomal RNA sequencing.ConclusionThe results proved that MSCs could migrate to the colon, inhibit chronic inflammation, and regulate gut microbiome dysbiosis to suppress the development of CAC.

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Clinical significance of serum angiopoietin-like protein 2 in colorectal cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.417 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 417-417

Author(s):

Takahito Kitajima ◽

Yuji Toiyama ◽

Tadanobu Shimura ◽

Shozo Ide ◽

Hiroki Imaoka ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Cell ◽

Cancer Patients ◽

Clinical Significance ◽

Prognostic Significance ◽

Disease Free Survival ◽

Staining Intensity ◽

High Serum ◽

Highly Correlated ◽

Colorectal Cancer Patients

417 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted protein belonging to the angiopoietin family. It has been reported to act as a causative mediator of chronic inflammation and metabolic abnormalities. ANGPTL2 increases inflammatory carcinogenesis in several cancers, and its expression in tumor cells is highly correlated with the frequency of tumor cell metastasis through increased tumor angiogenesis and tumor cell epithelial-to-mesenchymal transitions. However, to our own knowledge, clinical significance of serum ANGPTL2 in cancer patients remains unknown. The aim of this study was to quantify serum ANGPTL2 level using ELISA, and to evaluate its clinical and prognostic significance in patients with colorectal cancer (CRC). Methods: We quantified serum ANGPTL2 levels from 194 CRC patients and normal 48 controls (NC) by ELISA. Next, we investigated ANGPTL2 expression in matched CRC tissues (n=194) by immunohistochemistry (IHC) to identify the source of circulating ANGPTL2. The IHC score of ANGPTL2 was determined on the basis of both staining intensity and the percentage of positive cells. Results: Serum ANGPTL2 levels were significantly higher in CRC than in NC (p<0.01) and gradually increased according to TNM stage progression. Serum ANGPTL2 levels discriminated CRC from NC with high accuracy (AUC=0.837). High serum ANGPTL2 was significantly associated with larger tumor size (p=0.03), undifferentiated adenocarcinoma (p=0.03), advanced T stage (p<0.01), peritoneal metastasis (p<0.01). In addition, Kaplan–Meier curves revealed that high serum ANGPTL2 were significantly associated with poor disease free survival (p=0.01) and overall survival (p=0.03). Interestingly, ANGPTL2 levels in serum from CRC patients closely correlated with IHC scores of cytoplasmic ANGPTL2 expression in matched CRC tissues (r=0.14, p=0.03). Conclusions: Serum ANGPTL2, which might be derived from primary CRC tumor, has strong potential to serve as a noninvasive biomarker for CRC diagnosis and prognosis.

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Clinical significance of isolated tumor cell detection in peripheral blood in breast cancer patients three years after diagnosis. Comparison between analysis of peripheral blood and bone marrow

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.14_suppl.9554 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 9554-9554

Author(s):

B. Naume ◽

G. Wiedswang ◽

E. Borgen ◽

C. Schirmer ◽

G. Kvalheim ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Tumor Cell ◽

Cancer Patients ◽

Clinical Significance ◽

Peripheral Blood ◽

Cell Detection ◽

Breast Cancer Patients ◽

Tumor Cell Detection ◽

Isolated Tumor Cell

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Clinical significance of isolated tumor cell detection in peripheral blood in breast cancer patients three years after diagnosis. Comparison between analysis of peripheral blood and bone marrow

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.90140.9554 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 9554-9554 ◽

Cited By ~ 1

Author(s):

B. Naume ◽

G. Wiedswang ◽

E. Borgen ◽

C. Schirmer ◽

G. Kvalheim ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Tumor Cell ◽

Cancer Patients ◽

Clinical Significance ◽

Peripheral Blood ◽

Cell Detection ◽

Breast Cancer Patients ◽

Tumor Cell Detection ◽

Isolated Tumor Cell

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Clinical significance of golgi protein‐73 as a diagnostic marker for Egyptian patients with colorectal cancer: Preliminary study

Cancer Reports ◽

10.1002/cnr2.1379 ◽

2021 ◽

Author(s):

Shaymaa Abdelraheem Abdelhady ◽

Heba Attya ◽

Mohamed Abdo ◽

Fadia M. Attia

Keyword(s):

Colorectal Cancer ◽

Clinical Significance ◽

Diagnostic Marker ◽

Egyptian Patients ◽

Preliminary Study ◽

Golgi Protein

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Prognostic significance of bone marrow and spleen 18F-FDG uptake in patients with colorectal cancer

Scientific Reports ◽

10.1038/s41598-021-91608-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jae-Hoon Lee ◽

Hye Sun Lee ◽

Soyoung Kim ◽

Eun Jung Park ◽

Seung Hyuk Baik ◽

...

Keyword(s):

Colorectal Cancer ◽

Bone Marrow ◽

Inflammatory Markers ◽

Univariate Analysis ◽

Prognostic Significance ◽

Uptake Ratio ◽

Liver Uptake ◽

Fdg Uptake ◽

Standardized Uptake Values ◽

Serum Inflammatory Markers

AbstractSerum inflammatory markers are used in the prognostication of colorectal cancer (CRC); however, the corresponding role of positron emission tomography (PET)-derived inflammatory markers remains unclear. This study aimed to investigate the prognostic value of 18F-fluorodeoxyglucose (FDG) uptake in the bone marrow and spleen of patients with CRC and evaluate the relationship between FDG uptake estimates in these organs and serum inflammatory markers. In total, 411 patients who underwent preoperative FDG PET/computed tomography (CT) within 1 month of surgery were enrolled. The mean standardized uptake values of the bone marrow and spleen were normalized to the value of the liver, thereby generating bone marrow-to-liver uptake ratio (BLR) and spleen-to-liver uptake ratio (SLR) estimates. The value of BLR and SLR in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between BLR or SLR and neutrophil-to-lymphocyte ratio (NLR) was evaluated. The predictive accuracy of BLR alone and in combination with SLR was compared using the integrated area under the receiver operating characteristic curves (iAUC). In the univariate analysis, BLR (> 1.06) and SLR (> 0.93) were significant predictors of OS. In the multivariate analysis, BLR was an independent predictor of OS (hazard ratio = 5.279; p < 0.001). Both BLR and SLR were correlated with NLR (p < 0.001). A combination of BLR and SLR was better than BLR alone at CRC prognostication (iAUC, 0.561 vs. 0.542). FDG uptake estimates in the bone marrow and spleen may be useful imaging-derived biomarkers of systemic inflammation, supporting CRC prognostication.

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Circulating tumor cell-related transcripts in blood as prognostic biomarkers of early recurrence after liver resection for colorectal metastases

The International Journal of Biological Markers ◽

10.1177/1724600819849438 ◽

2019 ◽

Vol 34 (3) ◽

pp. 269-275

Author(s):

Felice Giuliante ◽

Elena Panettieri ◽

Francesco Ardito ◽

Agostino De Rose ◽

Krizia Pocino ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Resection ◽

Tumor Cell ◽

Carcinoembryonic Antigen ◽

Growth Factor Receptor ◽

Predictive Biomarker ◽

Circulating Tumor Cell ◽

Early Recurrence ◽

Colorectal Metastases

Background: Several prognostic factors were proposed to improve early detection of recurrence after liver resection of metastases of colorectal cancer. Circulating tumor cell-related transcripts were evaluated in colorectal cancer patients with conflicting results. The aim of this study was to investigate usefulness of carcinoembryonic antigen CAM5, epidermal growth factor receptor, and ERCC1 transcripts in the bloodstream as predictive factors of recurrence in patients who underwent liver resection for metastases of colorectal cancer. Methods: Peripheral blood was collected from 29 patients at the time of the colorectal cancer liver metastasis resection, and from 25 normal controls. Follow-up draws (FUDs) were also performed at 30 days, and 3 and 12 months since surgery. On each sample, carcinoembryonic antigen CAM5, ERCC1, and GAPDH mRNAs were examined by quantitative reverse transcription (qRT). Results: Carcinoembryonic antigen transcript levels were linearly correlated to the number of spiked cells (qRT analytical limit = five cells). Among 29 patients (20 M/9 F; mean age 63 years (range 32–79), highly significant levels of carcinoembryonic antigen, if compared to the baseline, were detected in those relapsing after surgery ( P <0.05). The main differences were between the 1st- and 12th-month FUDs. Significantly higher levels of carcinoembryonic antigen were also detected in patients who died from disease progression during the follow-up (as evaluated at 30 days and 90 days FUDs). Conclusions: Blood carcinoembryonic antigen-mRNA absolute copy number overtime variation can represent a valid early predictor of relapse after liver resection in colorectal liver metastases patients. Prospective studies, in the context of large clinical trials, will provide further data to also qualify ERCC1 as a predictive biomarker for decisions on therapeutic strategies.

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