High expression of CD73 as a poor prognostic biomarker in human colorectal cancer

Wu, Xianrui; He, Xiaosheng; Chen, Yufeng; Yuan, Ruixue; Zeng, Yang; Lian, Lei; Zou, Yifeng; Lan, Nan; Wu, Xiaojian; Lan, Ping

doi:10.1002/jso.23056

Cited by 143 publications

(114 citation statements)

References 37 publications

(52 reference statements)

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“…This result is in agreement with the literature that shows the increase of ecto-5′-NT/CD73 expression in many other cancers such as breast cancer, glioma, and melanoma [19,23,56]. Furthermore, ecto-5′-NT/CD73 overexpression promotes invasion, migration, adhesion, and metastasis of human breast cancer cells [20,57], indicating higher invasiveness and metastatic capability to melanomas [56,58] and poor prognosis in human colorectal cancer [22]. Ecto-5′-NT/CD73 expression in cancer cells has been also linked with drug resistance [26,59] and immune escape [44,60].…”

Section: Discussionsupporting

confidence: 92%

“…The final dephosphorylation of nucleotides, conversion of nucleoside monophosphates (e.g., AMP) to their respective nucleosides (e.g., adenosine), is catalyzed by ecto-5′-nucleotidase/CD73 (ecto-5′-NT/CD73). This enzyme is highly expressed in a variety of solid tumors [19][20][21][22] and has both its enzymatic activity and its adhesion protein function associated with cancer progression [23,24]. Besides, ecto-5′-NT/CD73 was found to be involved in cancer cell growth, maturation, differentiation, adhesion, migration, invasiveness, metastasis, immune escape, and drug resistance [19,[21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

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NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Rockenbach

Braganhol

Dietrich

et al. 2014

Purinergic Signalling

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According to the World Health Organization, bladder cancer is the seventh most common cancer among men in the world. The current treatments for this malignancy are not efficient to prevent the recurrence and progression of tumors. Then, researches continue looking for better therapeutic targets which can end up in new and more efficient treatments. One of the recent findings was the identification that the purinergic system was involved in bladder tumorigenesis. The ectonucleotidases, mainly ecto-5′-nucleotidase/CD73 have been revealed as new players in cancer progression and malignity. In this work, we investigated the NTPDase3 and ecto-5′-nucleotidase/CD73 expression in cancer progression in vivo. Bladder tumor was induced in mice by the addition of 0.05 % of N-butyl-N-(hydroxybutyl)-nitrosamine (BBN) in the drinking water for 4, 8, 12, 18, and 24 weeks. After this period, mice bladders were removed for histopathology analysis and immunofluorescence assays. The bladder of animals which has received BBN had alterations, mainly inflammation, in initial times of tumor induction. After 18 weeks, mice's bladder has developed histological alterations similar to human transitional cell carcinoma. The cancerous urothelium, from mice that received BBN for 18 and 24 weeks, presented a weak immunostaining to NTPDase3, in contrast to an increased expression of ecto-5′-nucleotidase/CD73. The altered expression of NTPDase3 and ecto-5′-nucleotidase/ CD73 presented herein adds further evidence to support the idea that alterations in ectonucleotidases are involved in bladder tumorigenesis and reinforce the ecto-5′-nucleotidase/ CD73 as a future biomarker and/or a target for pharmacological therapy of bladder cancer.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Rockenbach

Braganhol

Dietrich

et al. 2014

Purinergic Signalling

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“…CD73 was initially identified as a cell surface antigen that was specific to hematopoietic stem cells and functioned in a number of physiological processes in various normal human tissues, including hypoxic adaptation, ischemic preconditioning and inflammation (15)(16)(17). CD73 is reportedly activated in aggressive breast cancer, gastric and pancreatic cancers and lymphoma, and may be used as a prognostic marker for these tumors (18,19). The protective role of CD73 in renal ischemia (20) and the absence of tubuloglomerular feedback responses in CD73-deficient mice (14) have indicated the important role of CD73 in the function of renal tissue.…”

Section: Introductionmentioning

confidence: 99%

“…A high level of CD73 expression is associated with a poor prognosis in colorectal cancer (38). However, the role of CD73 expression in cancer cells in determining the prognosis of patients remains controversial in breast cancer (29,(38)(39)(40), which may be due to the conversion of adenosine that is promoted by CD73 in tumors.…”

mentioning

confidence: 99%

“…However, the role of CD73 expression in cancer cells in determining the prognosis of patients remains controversial in breast cancer (29,(38)(39)(40), which may be due to the conversion of adenosine that is promoted by CD73 in tumors. In the present cohort of RCC patients, intense CD73 protein expression in cancer cells was associated with a Inf lammator y hypoxia (14), hypoxia inducible factor-1 (HIF-1) (41) and Wnt signaling (42,43) are potent transcriptional stimuli for CD73 expression, which implies that the microenvironment of malignant tumors elevates CD73 expression.…”

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confidence: 99%

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Ecto-5′-nucleotidase expression is associated with the progression of renal cell carcinoma

Wang

Song

et al. 2015

Oncology Letters

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Abstract. Renal cell carcinoma (RCC) is a common tissue tumor that occurs across all age groups and has become one of the types of cancer with the fastest increasing incidence. Due to the resistance of RCC chemo-and radiotherapy, surgery is the only currently effective treatment. Therefore, specific markers for the diagnosis and prognosis of RCC are expected to result in novel methods of treatment. Ecto-5'-nucleotidase, also termed cluster of differentiation (CD)73, is a protein that is activated in several types of aggressive cancer and may promote cancer progression. CD73 was examined in the present study to determine the association between the protein and RCC. The expression levels of CD73 in 159 RCC tissue sections and 30 paratumorous normal renal tissue samples obtained from 235 patients that underwent nephrectomy were examined by immunohistochemical staining. By contrast, the expression level of P-glycoprotein (P-gp), a potential prognostic factor in RCC, was also examined in 85 RCC and 13 normal tissue samples. Intense CD73 expression was identified in 75 out of 159 RCC cell membranes compared with normal renal tissues. In contrast, there was high P-gp expression in the blood vessels of 42 out of 85 RCC tissues and there was no significant difference between the P-gp expression identified in RCC cells (34 out of 85) and the cell membrane of normal renal cells (2 out of 13). The expression level of CD73 in RCC cells was significantly associated with tumor type, tumor node metastasis (TNM) stage, and tumor grade. However, the expression of P-gp in RCC cells was only associated with the TNM stage and tumor grade. Using a multivariable Cox regression analysis, it was found that the median survival rate of RCC patients with intense CD73 expression in RCC cells was 62.06±5.35 months, which was drastically shorter compared with rare CD73 expression (103.72±3.67 months). In conclusion, the expression level of CD73 is significantly associated with RCC tumor progression and may serve as a favorable marker for the diagnosis and prognosis of RCC, in addition to being a therapeutic target for the treatment of RCC.

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A novel adenosine signalling‐based prognostic signature in gastric cancer and its association with cancer immune features and immunotherapy response

Wang

et al. 2023

Cell Biology International

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Reliable prognostic signatures that can reflect the intrinsic characteristics of gastric cancer (GC) are still rare. Here, we developed an adenosine‐based prognostic signature and explored its association with the tumour immune in GC patients, aiming at confirming the prognostic value of adenosine‐related genes and guiding the GC risk stratification and immunotherapeutic response prediction. We collected adenosine pathway‐related genes from STRING websites and manual searching. We enrolled the The Cancer Genome Atlas cohort and four gene expression omnibus cohorts of GC for generating and validating the adenosine pathway‐based signature using the Cox regression method. Gene expression in the signature was verified using polymerase chain reaction. We also performed gene set enrichment analysis, immune infiltration assessment and immunotherapy response prediction based on this signature. Our study resulted in a six‐gene adenosine signature (GNAS, CXCR4, PPP1R1B, ADCY6, NT5E and NOS3) for risk stratification of GC prognosis, with the highest area under the receiver operating characteristic curve up to 0.767 for predicting 10‐year overall survival (OS). In the training cohort, patients with signature‐defined high risk had significantly poorer OS than those with low risk (p < .001). Multivariate analysis identified the signature as an independent prognostic factor (hazard ratio 2.863, 95% confidence interval [1.871–4.381], p < .001). These findings were confirmed in four independent cohorts. Expression detection showed that all signature genes were upregulated in both GC tissues and cell lines. Further analysis revealed that the signature‐defined high‐risk patients were characterised by immunosuppressive states and associated with a poor immunotherapy response. In conclusion, the adenosine pathway‐based signature represents a promising risk stratification tool for GC in guiding individualised prognostication and immunotherapy.

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High expression of CD73 as a poor prognostic biomarker in human colorectal cancer

Abstract: High expression of CD73 can be an independent and useful biomarker for predicting the poor survival of patients with CRC.

Cited by 143 publications

References 37 publications

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Ecto-5′-nucleotidase expression is associated with the progression of renal cell carcinoma

A novel adenosine signalling‐based prognostic signature in gastric cancer and its association with cancer immune features and immunotherapy response

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