See the published version of this preprint at Cancer Cell International.
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Primary research
Yonghua Wang
Affiliated Hospital of Medical College Qingdao University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8861-1003
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and a high recurrence rate. Current studies indicated that metabolism-associated genes (MAGs) having critical roles in the etiology of BC. The present study aims to identify differentially expressed MAGs and construct a MAGs based prognostic risk signature for BC by using The Cancer Genome Atlas (TCGA) database and proteomics data.
Methods: RNA-sequence data from the TCGA database and proteomics data from our BC samples were used to identify differentially expressed MAGs and construct a MAGs based prognostic signature in BC. Subsequently, survival analysis and nomogram were used to evaluate the prognostic and predictive value of the MAGs based signature in BC. RNA isolation and reverse transcription‑quantitative PCR (RT-qPCR) were further performed to investigate the expression levels of MAGs in BC cells and explore the relationship between MAGs and M2 tumor associated macrophages (TAMs) secreted transforming growth factor-β1 (TGF-β1) in BC cells.
Results: A total of 23 differentially expressed MAGs were identified and five MAGs were finally used to construct a MAGs based signature. Survival analysis revealed that the MAGs based signature was closely correlated with the survival outcomes of patients with BC. A nomogram with the MAGs based signature risk score and clinical features was also constructed to facilitate the individualized prediction of BC patients. RT-qPCR showed that five MAGs were significantly differentially expressed and the expression levels of three MAGs were positively correlated with M2 TAMs secreted TGF-β1 in T24 cells.
Conclusions: Our study identified novel prognostic MAGs and constructed a MAGs based signature, which can be used as an independent factor in evaluating the prognosis of patients with BC. Furthermore, M2 TAMs may promote the expression of MAGs via the TGF-β1 signaling pathway in the microenvironment of BC. Further clinical trials and experimental explorations are needed to validate our observations in BC.
Keywords
bladder cancer, metabolism, TGF-β1, prognosis, TCGA
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This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1.tif
Additional file 1 The process of proteomic profiling. The process contained protein extraction, trypsin digestion, TMT/iTRAQ Labeling, HPLC Fractionation, LC-MS/MS Analysis, Database Search, and bioinformatic methods.
- Additionalfile2.docx
- Additionalfile3.tif
Additional file 3 The production of TGF-β1 in M2 TAM cells. Compare to M2 TAM cells without TGF-β1 inhibitor, the production of TGF-β1 in M2 TAM cells with TGF-β1 inhibitor were significantly decreased. *P < 0.05; **P < 0.005; ***P < 0.0005
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CURRENT STATUS: Published
View the published article at Cancer Cell International.
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Posted 27 Oct, 2020
No community comments so far
Editorial decision: Accept
On 25 Oct, 2020
Editor assigned
On 20 Oct, 2020
Reviewers invited
Invitations sent on 20 Oct, 2020
Reviewer #1 agreed
On 20 Oct, 2020
Reviewer #2 agreed
On 20 Oct, 2020
Review #1 received
Received 20 Oct, 2020
Review #2 received
Received 20 Oct, 2020
Submission checks complete
On 19 Oct, 2020
Editor invited
On 19 Oct, 2020
No comments provided
Editorial decision: Major revision
On 02 Oct, 2020
Review #1 received
Received 30 Sep, 2020
Review #3 received
Received 29 Sep, 2020
Reviewers invited
Invitations sent on 29 Sep, 2020
Reviewer #1 agreed
On 29 Sep, 2020
Reviewer #2 agreed
On 29 Sep, 2020
Reviewer #3 agreed
On 29 Sep, 2020
Review #2 received
Received 29 Sep, 2020
Editor assigned
On 28 Sep, 2020
Submission checks complete
On 27 Sep, 2020
Editor invited
On 27 Sep, 2020
No comments provided
Editorial decision: Major revision
On 10 Sep, 2020
Review #1 received
Received 04 Sep, 2020
Reviewer #3 agreed
On 02 Sep, 2020
Review #2 received
Received 02 Sep, 2020
Reviewer #2 agreed
On 21 Aug, 2020
Reviewer #1 agreed
On 20 Aug, 2020
Editor assigned
On 19 Aug, 2020
Reviewers invited
Invitations sent on 19 Aug, 2020
Submission checks complete
On 18 Aug, 2020
Editor invited
On 18 Aug, 2020
First submitted
On 13 Aug, 2020
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Subject Areas
Cancer Biology
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at Cancer Cell International.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Primary research
Yonghua Wang
Affiliated Hospital of Medical College Qingdao University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8861-1003
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Cancer Cell International.
Version 3
Posted 27 Oct, 2020
No community comments so far
Editorial decision: Accept
On 25 Oct, 2020
Editor assigned
On 20 Oct, 2020
Reviewers invited
Invitations sent on 20 Oct, 2020
Reviewer #1 agreed
On 20 Oct, 2020
Reviewer #2 agreed
On 20 Oct, 2020
Review #1 received
Received 20 Oct, 2020
Review #2 received
Received 20 Oct, 2020
Submission checks complete
On 19 Oct, 2020
Editor invited
On 19 Oct, 2020
No comments provided
Editorial decision: Major revision
On 02 Oct, 2020
Review #1 received
Received 30 Sep, 2020
Review #3 received
Received 29 Sep, 2020
Reviewers invited
Invitations sent on 29 Sep, 2020
Reviewer #1 agreed
On 29 Sep, 2020
Reviewer #2 agreed
On 29 Sep, 2020
Reviewer #3 agreed
On 29 Sep, 2020
Review #2 received
Received 29 Sep, 2020
Editor assigned
On 28 Sep, 2020
Submission checks complete
On 27 Sep, 2020
Editor invited
On 27 Sep, 2020
No comments provided
Editorial decision: Major revision
On 10 Sep, 2020
Review #1 received
Received 04 Sep, 2020
Reviewer #3 agreed
On 02 Sep, 2020
Review #2 received
Received 02 Sep, 2020
Reviewer #2 agreed
On 21 Aug, 2020
Reviewer #1 agreed
On 20 Aug, 2020
Editor assigned
On 19 Aug, 2020
Reviewers invited
Invitations sent on 19 Aug, 2020
Submission checks complete
On 18 Aug, 2020
Editor invited
On 18 Aug, 2020
First submitted
On 13 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Cancer Cell International.
Background: Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and a high recurrence rate. Current studies indicated that metabolism-associated genes (MAGs) having critical roles in the etiology of BC. The present study aims to identify differentially expressed MAGs and construct a MAGs based prognostic risk signature for BC by using The Cancer Genome Atlas (TCGA) database and proteomics data.
Methods: RNA-sequence data from the TCGA database and proteomics data from our BC samples were used to identify differentially expressed MAGs and construct a MAGs based prognostic signature in BC. Subsequently, survival analysis and nomogram were used to evaluate the prognostic and predictive value of the MAGs based signature in BC. RNA isolation and reverse transcription‑quantitative PCR (RT-qPCR) were further performed to investigate the expression levels of MAGs in BC cells and explore the relationship between MAGs and M2 tumor associated macrophages (TAMs) secreted transforming growth factor-β1 (TGF-β1) in BC cells.
Results: A total of 23 differentially expressed MAGs were identified and five MAGs were finally used to construct a MAGs based signature. Survival analysis revealed that the MAGs based signature was closely correlated with the survival outcomes of patients with BC. A nomogram with the MAGs based signature risk score and clinical features was also constructed to facilitate the individualized prediction of BC patients. RT-qPCR showed that five MAGs were significantly differentially expressed and the expression levels of three MAGs were positively correlated with M2 TAMs secreted TGF-β1 in T24 cells.
Conclusions: Our study identified novel prognostic MAGs and constructed a MAGs based signature, which can be used as an independent factor in evaluating the prognosis of patients with BC. Furthermore, M2 TAMs may promote the expression of MAGs via the TGF-β1 signaling pathway in the microenvironment of BC. Further clinical trials and experimental explorations are needed to validate our observations in BC.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
- Additionalfile1.tif
Additional file 1 The process of proteomic profiling. The process contained protein extraction, trypsin digestion, TMT/iTRAQ Labeling, HPLC Fractionation, LC-MS/MS Analysis, Database Search, and bioinformatic methods.
- Additionalfile2.docx
- Additionalfile3.tif
Additional file 3 The production of TGF-β1 in M2 TAM cells. Compare to M2 TAM cells without TGF-β1 inhibitor, the production of TGF-β1 in M2 TAM cells with TGF-β1 inhibitor were significantly decreased. *P < 0.05; **P < 0.005; ***P < 0.0005
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