Dataset Information

Clinical values of circulating tumor cells count in localized renal cell carcinoma.

ABSTRACT:

Background

Renal cancer is one of the most common malignant tumors of the urinary system, with distant metastasis occurring 30% of patients. Therefore, early detection and monitoring of tumor progression are of great significance in the diagnosis and treatment of renal cancer. However, current biomarkers used to diagnose, monitor recurrence and assess prognosis of renal cancer are still uncertain. Circulating tumor cells (CTCs) are tumor cells detached from the primary tumor or metastasis, invaded and existing in the peripheral blood, and are one of the most promising liquid biopsy targets because they can provide complete cell biological information. Microfluidic chip has advantages of miniaturization, high integration, and fast analysis, which has advantages in CTC separation and enrichment.

Methods

In this study, 1 mL peripheral blood of each 30 patients with early localized renal cancer was collected before and 1 day after surgery. CTC enrichment was performed by microfluidic chip and CTCs were identified by immunofluorescence staining. All patients were followed up for a median of 17 months.

Results

The number of CTCs before surgery was higher than that after surgery (P<0.001), and the number was positively correlated with tumor-node-metastasis (TNM) stage and International Society of Urological Pathology (ISUP) grade. Patients in group CTC ≤2 had a longer progression-free survival (PFS) than those in group CTC ≥3 (P<0.05).

Conclusions

Surgical treatment can remarkably reduce the number of CTCs in patients, and CTC counts can also play a role in monitoring tumor load and predicting prognosis in renal cancer.

SUBMITTER: Wang Q

PROVIDER: S-EPMC10583006 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Publications

Clinical values of circulating tumor cells count in localized renal cell carcinoma.

Wang Qirui Q Li Zhile Z Zhai Wei W Zheng Junhua J

Translational cancer research 20230809 9

<h4>Background</h4>Renal cancer is one of the most common malignant tumors of the urinary system, with distant metastasis occurring 30% of patients. Therefore, early detection and monitoring of tumor progression are of great significance in the diagnosis and treatment of renal cancer. However, current biomarkers used to diagnose, monitor recurrence and assess prognosis of renal cancer are still uncertain. Circulating tumor cells (CTCs) are tumor cells detached from the primary tumor or metastasi ...[more]

PMID: 37859739

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Project description:BackgroundThe tumor immune microenvironment has become the focus of research in clear cell renal cell carcinoma (ccRCC) due to its important role in immune surveillance post nephrectomy. This study investigates the correlation of tumor infiltrating immune cell characteristics with rates of recurrence following surgery in localized ccRCC.MethodsWe morphologically identified and scored tumor infiltrating lymphocytes (TILs) in hematoxylin and eosin (H&E) stained slides of patients with localized ccRCC (stage ≥T1b excluding stage IV). The University of Alabama at Birmingham (UAB) dataset (n = 159) was used to discover and the Fox Chase Cancer Center (FCCC) dataset (n = 198) was used to validate the results of morphologic immune cell analysis. We then performed gene expression analysis using the Immune Profile panel by NanoString in the UAB cohort and identified immune cells and pathways associated with recurrence, followed by validation in the Cancer Genome Atlas (TCGA) ccRCC dataset. Infiltrating immune cell types were identified by gene expression deconvolution.ResultsThe presence of TILs identified by morphology correlated with higher T cell, Th1, CD8+ T and Treg gene signatures. Recurrence was associated with lower T cells and higher neutrophils. Higher Teffector (Teff)/Treg ratio correlated with lower rate of recurrence and was validated in the TCGA dataset. Genes associated with adaptive immune response were downregulated in tumors that recurred. Unsupervised hierarchical clustering identified a subset of patients with over-expression of adaptive response genes including CD8, CD3, GZMA/B, PRF1, IDO1, CTLA4, PDL1, ICOS and TIGIT. These patients had higher morphologic lymphocyte infiltration and T cell gene expression. Higher levels of TILs identified by morphology correlated with higher rates of recurrence in our discovery dataset but not in our validation set.ConclusionsRecurrence of ccRCC following surgery was associated with lower T cell infiltrate, lower adaptive immune response and higher neutrophil gene expression. Presence of higher Teff/Treg ratio correlated with lower recurrence.

Project description:BackgroundCirculating tumor cells (CTCs) correlate with adverse prognosis in patients with breast, colorectal, lung, and prostate cancer. Little data are available for renal cell carcinoma (RCC).Materials and methodsWe designed a multicenter prospective observational study to assess the correlation between CTC counts and progression-free survival (PFS) in patients with metastatic RCC treated with an antiangiogenic tyrosine kinase inhibitor as a first-line regimen; overall survival (OS) and response were secondary objectives. CTC counts were enumerated by the CellSearch system at four time points: day 0 of treatment, day 28, day 56 and then at progression, or at 12 months in the absence of progression.ResultsOne hundred ninety-five eligible patients with a median age of 69 years were treated with sunitinib (77.5%) or pazopanib (21%). At baseline, 46.7% of patients had one or more CTCs per milliliter (range, 1 to 263). Thirty patients had at least three CTCs, with a median PFS of 5.8 versus 15 months in the remaining patients (p = .002; hazard ratio [HR], 1.99), independently of the International Metastatic RCC Database Consortium score at multivariate analysis (HR, 1.91; 95% confidence interval [CI], 1.16-3.14). Patients with at least three CTCs had a shorter estimated OS of 13.8 months versus 52.8 months in those with fewer than three CTCs (p = .003; HR, 1.99; multivariate analysis HR, 1.67; 95% CI, 0.95-2.93). Baseline CTC counts did not correlate with response; neither did having CTC sequencing counts greater than or equal to one, two, three, four, or five.ConclusionWe provide prospective evidence that the presence of three or more CTCs at baseline is associated with a significantly shorter PFS and OS in patients with metastatic RCC.Implications for practiceThis prospective study evaluated whether the presence of circulating tumor cells (CTCs) in the peripheral blood correlates with activity of first-line tyrosine kinase inhibitors in metastatic renal cell carcinoma (RCC). This study demonstrated that almost half of patients with metastatic RCC have at least one CTC in their blood and that those patients with at least three CTCs are at increased risk of early progressive disease and early death due to RCC. Studies incorporating CTC counts in the prognostic algorithms of metastatic RCC are warranted.

Dataset Information

Clinical values of circulating tumor cells count in localized renal cell carcinoma.

Background

Methods

Results

Conclusions

Publications

Clinical values of circulating tumor cells count in localized renal cell carcinoma.

Similar Datasets

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