Kras mutation correlating with circulating regulatory T cells predicts the prognosis of advanced pancreatic cancer patients

He, Cheng; Luo, Guopei; Jin, Kaizhou; Fan, Zhichao; Huang, Qiuyi; Gong, Yitao; Xu, Jin; Yu, Xianjun; Liu, Chen

doi:10.1002/cam4.2895

Cited by 25 publications

(24 citation statements)

References 33 publications

(73 reference statements)

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“…The mutations and concentration levels of ctDNA may be associated with overall survival (OS) and progression-free survival (PFS) in PC patients. Our previous studies demonstrated that K-ras mutations and ERBB2 exon17 mutations detected in ctDNA are significantly associated with OS [ 18 – 20 ]. However, inconsistent findings have been reported [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of circulating tumor DNA in pancreatic cancer: a systematic review and meta-analysis

Fang

Meng

Zhang

et al. 2020

Aging

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Increasing evidence has revealed the potential correlation between circulating tumor DNA (ctDNA) and the prognosis of pancreatic cancer, but inconsistent findings have been reported. Therefore, a meta-analysis was performed to evaluate the prognostic value of ctDNA in pancreatic cancer. The Embase, MEDLINE, and Web of Science databases were searched for relevant articles published until April 2020. Articles reporting the correlation between ctDNA and the prognosis of pancreatic cancer were identified through database searches. The pooled hazard ratios (HRs) for prognostic data were calculated and analyzed using Stata software. A total of 2326 patients pooled from 25 eligible studies were included in the meta-analysis to evaluate the prognostic value of ctDNA in pancreatic cancer. Patients with mutations detected or high concentrations of ctDNA had a significantly poorer overall survival (OS) (univariate: HR = 2.54; 95% CI, 2.05-3.14; multivariate: HR = 2.07; 95% CI, 1.69-2.54) and progression-free survival (PFS) (univariate: HR = 2.18; 95% CI, 1.41-3.37; multivariate: HR = 2.20; 95% CI, 1.38-3.52). In conclusion, the present meta-analysis indicates that mutations detected or high concentrations of ctDNA are significant predictors of OS and PFS in patients with pancreatic cancer.

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Section: Introductionmentioning

confidence: 99%

Prognostic value of circulating tumor DNA in pancreatic cancer: a systematic review and meta-analysis

Fang

Meng

Zhang

et al. 2020

Aging

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“…The presence of detectable ctDNA, at baseline or postoperative, in resectable pancreatic cancer patients was significant for the prognosis of disease recurrence and the overall survival. A few relevant studies were based on the analysis of DNA methylation in ctDNA and corroborated the prognostic and diagnostic utility of the ctDNA assay [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. The authors investigated the profile of promoter methylation of BNC1 and ADAMTS1 genes using ctDNA.…”

Section: Ctdna In Pancreatic Cancermentioning

confidence: 99%

Detection of Circulating Tumor DNA in Solid Tumors

Testa¹,

Castelli²

2020

genetics

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Cancer is characterized by sequential and progressive genetic and epigenetic alterations in key proto-oncogenes and tumor suppressor genes, which ultimately lead to tumor development. Advances in the technology of analysis of molecular mechanisms have increased the efficiency of clinical management of cancer patients. Recent years have witnessed a progressive development in technologies that enable the detection of specific molecular abnormalities associated with various types of solid tumors in body fluids, a process that is globally known as "liquid biopsy". Liquid biopsy is largely based on the circulating free DNA (cfDNA) present in the plasma of healthy individuals and derived either from cell apoptosis or from the active secretion of microvesicles mediated by white blood cells (WBCs). The plasma of cancer patients contains DNA, which is referred to as circulating tumor DNA (ctDNA) and is released by the tumor cells in the form of DNA fragments of various sizes bearing the various types of genetic abnormalities specific to the tumors from which were derived. Sequencing studies conducted with several thousands of cancer patients have revealed that ctDNA accounts for only a fraction of the total DNA, and the size of this fraction varies in relation to tumor burden, tumor site, tumor subtypes, and several other biological properties of the tumor cells. Therefore, the levels of ctDNA are extremely low in several earlystage tumors, requiring highly sensitive methods for the detection of genetic alterations

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“…Previous studies demonstrated that Tregs are increased in many solid tumors [3][4][5][6], as well as hematopoietic malignancies [7][8][9]. In addition, an increased Treg frequency is related to poor prognosis [6,10,11].…”

Section: Introductionmentioning

confidence: 99%

Hyperfunction of CD4 CD25 regulatory T cells in de novo acute myeloid leukemia

Wan

Zhang

et al. 2020

BMC Cancer

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Background: Acute myeloid leukemia (AML) is a common hematopoietic malignancy that has a high relapse rate, and the number of regulatory T cells (Tregs) in AML patients is significantly increased. The aim of this study was to clarify the role of Tregs in the immune escape of acute myeloid leukemia. Methods: The frequencies of Tregs and the expression of PD-1, CXCR4 and CXCR7 were examined by flow cytometry. The expression of CTLA-4 and GITR was tested by MFI. Chemotaxis assays were performed to evaluate Treg migration. The concentrations of SDF-1α, IFN-γ and TNF-α were examined by ELISA. Coculture and crisscross coculture experiments were performed to examine Treg proliferation and apoptosis and the effect of regulatory B cells (Breg) conversion. Results: The frequencies of Tregs in peripheral blood and bone marrow in AML patients were increased compared with those in healthy participants. AML Tregs had robust migration towards bone marrow due to increased expression of CXCR4. AML Treg-mediated immunosuppression of T cells was achieved through proliferation inhibition, apoptosis promotion and suppression of IFN-γ production in CD4 + CD25 − T cells. AML Bregs induced the conversion of CD4 + CD25 − T cells to Tregs. Conclusion: In AML patients, the Breg conversion effect and robust CXCR4-induced migration led to Treg enrichment in bone marrow. AML Tregs downregulated the function of CD4 + CD25 − T cells, contributing to immune escape.

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Kras mutation correlating with circulating regulatory T cells predicts the prognosis of advanced pancreatic cancer patients

Cited by 25 publications

References 33 publications

Prognostic value of circulating tumor DNA in pancreatic cancer: a systematic review and meta-analysis

Prognostic value of circulating tumor DNA in pancreatic cancer: a systematic review and meta-analysis

Detection of Circulating Tumor DNA in Solid Tumors

Hyperfunction of CD4 CD25 regulatory T cells in de novo acute myeloid leukemia

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