scholarly journals The Presence of Circulating Tumor Cell Cluster Characterizes an Aggressive Hepatocellular Carcinoma Subtype

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing-Jing Yu ◽  
Chang Shu ◽  
Hui-Yuan Yang ◽  
Zhao Huang ◽  
Ya-Ni Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Cell ◽  
Rna Sequencing ◽  
Clinical Features ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Joint Analysis ◽  
Sequencing Analysis ◽  
Tumor Stages

BackgroundGrowing evidence suggests that circulating tumor cell (CTC) clusters may be an important factor in the metastatic process, but their role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to characterize the molecular and clinical features of CTC cluster-positive human HCC and to assess its prognostic value in HCC patients.MethodsThe CTCs and CTC clusters were evaluated in 204 HCC patients using CellSearch™ System. The counts of CTCs and CTC clusters were correlated with different clinical features, while their associations with progression-free survival (PFS) and overall survival (OS) were evaluated integrally and hierarchically by Kaplan–Meier estimates or Cox proportional regression analysis. Five cases each of CTC cluster-negative and cluster-positive patients were selected for RNA-sequencing analysis. The results of gene enrichment analysis were further verified using tissue microarray (TMA) by immunohistochemistry (IHC).ResultsCTCs and CTC clusters were detected in 76 (37.3%) and 19 (9.3%) of 204 preoperative samples, respectively. CTC cluster-positive HCC represented an aggressive HCC phenotype with larger tumor size, more frequent microvascular invasion, and higher tumor stages. The survival of HCC patients utilizing CTCs and CTC clusters individually showed prognostic significance, while joint analysis revealed patients in Group III (CTC ≥ 2 and CTC cluster > 0) had the worst outcome. Stratified analysis of outcomes in Barcelona Clinic Liver Cancer (BCLC) and tumor–node–metastasis (TNM) stages indicated that patients with CTC clusters had significantly poorer prognosis in each stage than those without CTC clusters. Moreover, the RNA sequencing and TMA staining results showed that CTC cluster-positive HCCs were usually associated with Wnt/β-catenin signaling activation.ConclusionThe presence of CTC clusters characterizes an aggressive HCC subtype. CTC clusters may be used as a biomarker in predicting the prognosis on each stage of malignancy in HCC, which provides evidence for formulating therapeutic strategies for more precise treatment.

Tumor-cell DNA content predicts outcome in children and adolescents with clinical group III embryonal rhabdomyosarcoma. The Intergroup Rhabdomyosarcoma Study Committee of the Children's Cancer Group and the Pediatric Oncology Group.

1993 ◽  
Vol 11 (10) ◽  
pp. 1901-1905 ◽  
Author(s):  
A S Pappo ◽  
W M Crist ◽  
J Kuttesch ◽  
S Rowe ◽  
R A Ashmun ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Dna Content ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Embryonal Rhabdomyosarcoma ◽  
Clinical Group ◽  
Anatomic Site ◽  
Cox Regression Analysis ◽  
Diploid Cells

PURPOSE The prognostic value of tumor-cell DNA content (ploidy) was evaluated in children with unresectable, nonmetastic rhabdomyosarcoma of embryonal histology. PATIENTS AND METHODS Flow-cytometric techniques were used to estimate the ploidy of tumor specimens from 34 patients with embryonal rhabdomyosarcoma who were enrolled in the intergroup rhabdomyosarcoma study III (IRS III) from 1985 to 1991. Tumors were classified as diploid or hyperdiploid (DNA content, 1.1 to 1.8 times that of normal diploid cells). The influence of ploidy on clinical outcome was assessed by the Kaplan-Meier technique and Cox regression analysis with stepwise selection. RESULTS Twelve of the tumor specimens were diploid and 22 were hyperdiploid. The patient groups defined by diploid or hyperdiploid tumors had similar presenting characteristics (eg, age, tumor size, and anatomic site). Significantly more children with hyperdiploid tumors achieved a complete response than did children with diploid tumors (85% v 42%; P = .01). The probability of progression-free survival at 5 years (+/- SE) was 91% +/- 6% for the hyperdiploid group, compared with 17% +/- 11% for the diploid group (P < .001). Hyperdiploidy was also associated with a significantly higher overall survival rate at 5 years: 96% +/- 4% versus 50% +/- 14% (P = .004). Ploidy retained its prognostic significance after adjustment for tumor site in the Cox regression model. CONCLUSION Tumor-cell ploidy strongly correlates with outcome in children with nonmetastic, unresectable embryonal rhabdomyosarcoma. The two biologically distinct groups identified by this measure would benefit from further refinements in risk-directed therapy.

scholarly journals The Prognostic Roles and Clinical Features of CD44v9 in Human Solid Cancers—A Meta-Analysis

2020 ◽  
Author(s):  
Yuanxiu Deng ◽  
Jie Wang ◽  
Shenhui Ji ◽  
Lu Huang ◽  
Meijiang Feng
Keyword(s):  
Clinical Features ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
High Expression ◽  
Cochrane Library ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Diagnosis And Prognosis

Abstract Background: CD44 is the primary receptor for hyaluronic acid and serves as a marker for cancer stem cells. CD44v9 is one of CD44’s variants and takes part in cancer’s growth and metastasis. However, the prognostic roles and clinical features of CD44v9 in cancers remain unclear. Therefore, we conducted this meta-analysis to summarize the prognostic significance and clinical features of CD44v9 in human solid cancers.Methods: we systematically searched all of related studies in PubMed, the Web of Science, Embase and Cochrane library up to June 2020. We analyzed the pooled hazard ratios (HRs) and odds ratios (ORs) with corresponding 95% confidence intervals (CIs) to assess the prognostic functions and clinical features of CD44v9 in various human solid cancers.Results: In this meta-analysis, we included 1705 cancer patients among 12 studies. Results indicated that high expression of CD44v9 was significantly related to poorer overall survival (OS) (HR=1.60, 95%CI 1.28-1.99, P<0.0001), recurrence-free survival/progression-free survival/disease-free survival (RFS/PFS/DFS).( HR=1.81, 95%CI 1.16-2.84, P=0.009) and disease-specific survival/cancer-specific survival (DSS/CSS) (HR=2.93, 95%CI 1.69-5.10, P<0.001). At the same time, we also found that high expression of CD44v9 increased the possibility of lymphoid infiltrates (OR=1.59, 95%CI 1.16-2.20, P=0.005), vascular invasion (OR=1.57, 95%CI 1.11-2.22, P=0.010) and higher TNM stage (OR=1.63, 95%CI 1.19-2.23, P=0.002).Conclusion: Our results demonstrate that CD44v9 overexpression is associated with worse OS, RFS/PFS/CFS and DSS/CSS in patients with solid cancers, which might be a biomarker in the diagnosis and prognosis of cancers in the future.

Prognostic significance of circulating tumor cell (CTC) levels at various times during first- and second-line chemotherapy for metastatic breast cancer (MBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21077-e21077
Author(s):  
Rafael Arteta-Bulos ◽  
Paul J. E. Miller ◽  
Rebecca S. Overbury ◽  
Alison Schwartzberg ◽  
Mark S. Walker ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Metastatic Breast ◽  
Community Setting ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Sensitivity Analyses ◽  
Prognostic Information ◽  
Treatment Regimens ◽  
Oncology Practice

e21077 Background: CTCs have prognostic capability in the treatment of MBC based on a dichotomous level of ≥5/7.5 ml blood (Hi) vs. <5/7.5 ml blood (Lo) at baseline and first follow-up. The value of CTCs beyond baseline is not well established, and the implication of values that are reduced but remain high has not been explored. Methods: Chart review of patients (pts) on 1st or 2nd line treatment of MBC, with CTC determinations between 2/2008 and 9/2011, were retrospectively identified at a large community oncology practice. Pts with ≥2 CTCs or 1 CTC ≥5 were eligible. Demographics, treatment regimens and progression-free survival (PFS) were assessed. The Veridex Cell Search system was utilized for all CTC determinations. Qualifying baseline CTCs were those drawn -14 days to +30 days from start of treatment. Results: 221 eligible pts were identified, 71 with baseline CTCs in 1st line, and 84 in 2nd line. Median age was 59.5 (range 26-90), 40.7% were African-American, 17.6% HER2+, and 63%/49% ER/PR+. The median time to baseline CTC was 5 days in the 1st line and 1 day in the 2nd line. 1st line PFS was 8.0 vs. 5.8 mo among baseline Hi vs. Lo groups (p = 0.085). 2nd line PFS was 3.7 vs. 4.0 mo for Hi and Lo groups, respectively, (ns). Follow-up CTCs were obtained at clinical convenience. A 90 day landmark was used for analysis of PFS by four baseline/follow-up CTC pattern groups. 1st line PFS showed medians ranging from 6.0 mo (Hi/Hi) to 10.2 mo (Lo/Lo). In 1st line pts with Hi baseline CTCs (n=24), median PFS was 6.0 vs. 7.0 mo for Hi vs. Lo at follow-up (p = .64). Grouping pts with Hi baseline CTCs by reductions in absolute CTC count at follow-up (<33% vs. ≥33%) showed median PFS 3.5 mo for <33% reduction, 8.8 mo for ≥33% reduction (p = .0179). Sensitivity analyses with other cutoffs in reduction from 20-80% showed similar results. Conclusions: In the community setting, baseline and subsequent CTCs obtained at various times after baseline yield clinically useful prognostic information. Pts with positive baseline CTC levels experiencing a reduction of ≥33% exhibit significantly longer PFS, indicating that a simple high/low approach to the test can be modified to yield more prognostic value.

Development and validation of circulating tumor cell (Epic Sciences) enumeration as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 157-157
Author(s):  
Howard I. Scher ◽  
Andrew J. Armstrong ◽  
Joseph D. Schonhoft ◽  
Audrey Gill ◽  
Jimmy Zhao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cell ◽  
Validation Cohort ◽  
Prognostic Significance ◽  
Circulating Tumor Cell ◽  
Cancer Center ◽  
Significant Prognostic Factor ◽  
Castration Resistant Prostate Cancer ◽  
Discovery Cohort ◽  
Castration Resistant

157 Background: We evaluated the prognostic significance of circulating tumor cell (CTC) number as determined on the Epic Sciences platform in men with metastatic castration resistant prostate cancer (mCRPC) treated with an androgen receptor signaling inhibitor (ARSI). Methods: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a 1st, 2nd or 3rd line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N=175) or as a 1st and 2nd line therapy as part of the multi-center PROPHECY trial (NCT02269982) (Validation cohort, N=107). Enumeration was performed on the Epic Sciences platform and associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. Matched blood samples from the Validation cohort were to CTC counts measured on the CellSearch Circulating Tumor Cell kit. Results: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (< 3 CTCs/mL versus ≥ 3 CTCs/mL; HR = 1.8, (1.3-3.0, 95% CI)) and as a continuous variable when adjusting for line of therapy, presence of visceral metastases, PSA, lactate-dehydrogenase, and alkaline-phosphatase. The findings were validated in an independent dataset (PROPHECY trial) - (HR (95% CI) = 1.8, (1.1-3.0) for OS and 1.7 (1.1-2.9), for PFS). A strong correlation was observed between CTC counts determined in matched samples on the CellSearch and Epic platforms (r = 0.84). Conclusions: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.

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