scholarly journals Evaluation of the Role of Circulating Tumor Cells and Microsatellite Instability Status in Predicting Outcome of Advanced CRC Patients

2020 ◽  
Vol 10 (4) ◽  
pp. 235
Author(s):  
Ippokratis Messaritakis ◽  
Maria Sfakianaki ◽  
Konstantinos Vogiatzoglou ◽  
Asimina Koulouridi ◽  
Chara Koutoulaki ◽  
...  

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death due to its high metastatic potential. This study aimed to investigate the detection and heterogeneity of circulating tumor cells (CTCs) and the microsatellite instability (MSI) status in advanced CRC patients prior to any systemic front-line treatment. Peripheral whole blood was obtained from 198 patients. CTCs were detected using double immunofluorescence and a real time-polymerase chain reaction assay; whereas MSI status was evaluated using fragment analysis. Median age of the patients was 66 years, 63.1% were males, 65.2% had a colon/sigmoid tumor location and 90.4% had a good performance status (PS). MSI-High status was detected in 4.9% of the patients; 33.3%, 56.1% and 8.6% patients had at least one detectable CEACAM5+/EpCAM+, CEACAM5+/EpCAM− and CEACAM5−/EpCAM+ CTC, respectively, and 9.1% of the patients had CEACAM5mRNA-positive CTCs. Following multivariate analysis, age, PS and MSI were confirmed as independent prognostic factors for decreased time to progression, whereas age, PS and CTC presence were confirmed as independent prognostic factors for decreased overall survival. In conclusion, our data support the use of CEACAM5 as a dynamic adverse prognostic CTC biomarker in patients with metastatic CRC and MSI-High is considered an unfavorable prognostic factor in metastatic CRC patient tumors.

2017 ◽  
Vol 24 (6) ◽  
pp. R223-R237 ◽  
Author(s):  
Maria Chiara Zatelli ◽  
Erika Maria Grossrubatscher ◽  
Elia Guadagno ◽  
Concetta Sciammarella ◽  
Antongiulio Faggiano ◽  
...  

The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Satu Salmi ◽  
Anton Lin ◽  
Benjamin Hirschovits-Gerz ◽  
Mari Valkonen ◽  
Niina Aaltonen ◽  
...  

Abstract Background FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) participate in the formation of an immunosuppressive tumor microenvironment (TME) in malignant cutaneous melanoma (CM). Recent studies have reported that IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. Methods We investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases (LNMs) of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells, and the coverage and intensity of IDO+ tumor cells were analysed. Results The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence˗free survival. We further showed that there was a positive correlation between IDO+ tumor cells and FoxP3+ Tregs. Conclusions These results indicate that IDO is strongly involved in melanoma progression. FoxP3+ Tregs also seems to contribute to the immunosuppressive TME in CM, but their significance in melanoma progression remains unclear. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies.


2016 ◽  
Vol 16 (8) ◽  
pp. 859-867 ◽  
Author(s):  
Nicola Normanno ◽  
Antonella De Luca ◽  
Marianna Gallo ◽  
Nicoletta Chicchinelli ◽  
Antonio Rossi

2018 ◽  
Vol 9 (5) ◽  
pp. 640-645 ◽  
Author(s):  
Bing Tong ◽  
Yan Xu ◽  
Jing Zhao ◽  
Minjiang Chen ◽  
Wei Zhong ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Chengcheng Qian ◽  
Renjie Cai ◽  
Wenying Zhang ◽  
Jiongyi Wang ◽  
Xiaohua Hu ◽  
...  

PurposeThe purpose of this study is to explore the prognostic value of associating pre-treatment neutrophil–lymphocyte ratio (NLR) with circulating tumor cells counts (CTCs) in patients with gastrointestinal cancer.Materials and MethodsWe collected the related data of 72 patients with gastric cancer (GC) and colorectal cancer (CRC) who received different therapies from August 2016 to October 2020, including age, gender, primary tumor location, TNM stage, tumor-differentiation, NLR, CTCs, disease-free survival (DFS) and overall survival (OS). We chose the optimal cut-off value of NLR >3.21 or NLR ≤3.21 and CTC >1 or CTC ≤1 by obtaining receiver operating characteristic (ROC) curve. The Kaplan–Meier survival analysis and Cox regression analysis were used to analyze DFS and OS. To clarify the role of the combination of NLR and CTCs counts in predicting the prognosis, we analyzed the DFS and OS when associated NLR and CTCs counts.ResultsA high NLR (>3.21) was associated with shorter DFS (P <0.0001) and OS (P <0.0001). Patients with high CTCs level (>1) had shorter DFS (P = 0.001) and OS (P = 0.0007) than patients with low CTCs level. Furthermore, patients who had both higher NLR and higher CTCs counts had obvious shorter DFS (P <0.0001) and OS (P <0.0001).ConclusionsPatients with higher NLR and more CTCs respectively tended to have poor prognosis with shorter DFS and OS, which might be regarded as predictors of gastrointestinal cancer. In particular, associating NLR and CTCs counts might be a reliable predictor in patients with gastrointestinal cancer.


2021 ◽  
Author(s):  
Julia Bonnet ◽  
Lise Rigal ◽  
Odile Mondesert ◽  
Renaud Morin ◽  
Gaelle Corsaut ◽  
...  

Abstract Background Cancer cell aggregation is a key process involved in the formation of tumor cell clusters. It has recently been shown that clusters of circulating tumor cells (CTCs) have an increased metastatic potential compared to isolated circulating tumor cells. Several widely used chemotherapeutic agents that target the cytoskeleton microtubules and cause cell cycle arrest at mitosis have been reported to modulate CTC number or the size of CTC clusters. Results In this study, we investigated in vitro the impact of mitotic arrest on the ability of breast tumor cells to form clusters. By using live imaging and quantitative image analysis, we found that MCF-7 cancer cell aggregation is compromised upon incubation with paclitaxel or vinorelbine, two chemotherapeutic drugs that target microtubules. In line with these results, we observed that MCF-7 breast cancer cells experimentally synchronized and blocked in metaphase aggregated poorly and formed loose clusters. To monitor clustering at the single-cell scale, we next developed and validated an in vitro assay based on live video-microscopy and custom-designed micro-devices. The study of cluster formation from MCF-7 cells that express the fluorescent marker LifeAct-mCherry using this new assay allowed showing that substrate anchorage-independent clustering of MCF-7 cells was associated with the formation of actin-dependent highly dynamic cell protrusions. Metaphase-synchronized and blocked cells did not display such protrusions, and formed very loose clusters that failed to compact. Conclusions Altogether, our results suggest that mitotic arrest induced by microtubule-targeting anticancer drugs prevents cancer cell clustering and therefore, could reduce the metastatic potential of circulating tumor cells.


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