RE: Reminder# cBioportal# OS for (Col6a3) by using cBioportal & KM plotter

[SHI, YUFEI]

Dear Niki:

 

Thank you for your prompt reply. The overall survival is still not significant after selection of over-expressed group although significant poor Disease-specific survival is observed. KM plotter does not calculate Disease-specific survival but shows significant poor overall survival. I would like to hear your comments.

 

Thank you,

Yufei

 

 

 

From: Schultz, Nikolaus <Schu...@mskcc.org>
Sent: Thursday, April 25, 2024 4:14 PM
To: SHI, YUFEI <yu...@kfshrc.edu.sa>
Cc: Satravada, Baby <Satr...@mskcc.org>; in...@cbioportal.org
Subject: Re: Reminder# cBioportal# OS for (Col6a3) by using cBioportal & KM plotter
Importance: High

 

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Hi Yufei,

 

Can you please send this email thread to the cBioPortal Google Group? That ensures that you will get a response. But the short answer is that you have to carefully select your “altered group” in the cBioPortal query. Your current query mixes samples with high and with low expression and compares those to samples with intermediated expression… 

 

cBioPortal for Cancer Genomics Discussion Group <cbiop...@googlegroups.com>

 

Thanks.

Niki.

 

On Apr 25, 2024, at 3:04 AM, SHI, YUFEI <yu...@kfshrc.edu.sa> wrote:

 

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Hello,

 

It was nice to meet you at AACR meeting at San Diago. As we discussed,  I am forwarding a previous email to you for your kind comments.  

 

Thank you and look forward for your reply.

 

Yufei

 

From: QATTAN, AMAL TALAT <aka...@kfshrc.edu.sa> 
Sent: Tuesday, July 25, 2023 7:16 AM
To: in...@cbioportal.org <in...@cbioportal.org>
Cc: SHI, YUFEI <yu...@kfshrc.edu.sa>
Subject: Reminder# cBioportal# OS for (Col6a3) by using cBioportal & KM plotter 
Importance: High

 

 

 

From: QATTAN, AMAL TALAT
Sent: Sunday, July 23, 2023 3:08 PM
To: in...@cbioportal.org
Cc: SHI, YUFEI
Subject: 23 July 2023# cBioportal# OS for (Col6a3) by using cBioportal & KM plotter 
Importance: High

 

Dear Sir,

We recently used both cBioPortal and KM plotter to predict the impact of Col6A3 overexpression on the overall survival (OS) of thyroid cancer patients. In cBioPortal, we analyzed all samples (500 samples/499 patients). To our surprise, KM plotter predicted poorer survival (logrank P=0.035), while cBioPortal did not show any significant difference. I would greatly appreciate it if you could explain the discrepancy.

Thank you,

Amal

 

Sincerely,

Amal Qattan, PhD

Scientist-Department of Molecular Oncology

Research & Innovation

King Faisal Specialist Hospital & Research Centre

Associate Professor, College of Medicine, Alfaisal University, Riyadh

KFSH&RC-Office-RC,3rd floor-312B

KFSH&RC, P.O.Box 3354,Riyadh 11211 (MBC#03)

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"Research is to see what everybody else has seen, and to think what nobody else has thought".  

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"Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less; in human beings of whom they know nothing". Voltaire 1694-1778.

 

From: SHI, YUFEI
Sent: Thursday, July 20, 2023 12:24 PM
Subject: OS for (Col6a3) by using KM plotter & cBioportal 
Importance: High

 

Hello,

 

We recently used both KM plotter and cBioPortal to predict Col6A3 overexpression on overall survival (OS) of thyroid cancer patients (TCGA thyroid mRNA-Seq dataset, n=502). To our surprise, KM plotter predicted poorer survival (logrank P=0.035) while cBioPortal predict no difference. I would appreciate very much if you can explain the difference. Please also make comments on the case number: N=7462 (is this total cancer cases or thyroid cancer cases?  The total cancer cases is 7489 while thyroid cancer cases is 502)  

 

 

 

https://www.cbioportal.org/results/comparison?cancer_study_list=thca_tcga_pan_can_atlas_2018&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=rna_seq_v2_mrna_median_all_sample_ref_normal_Zscores&case_set_id=thca_tcga_pan_can_atlas_2018_all&gene_list=COL6A3&geneset_list=%20&tab_index=tab_visualize&Action=Submit&comparison_selectedGroups=%5B%22LBH%22%2C%22FNDC4%22%2C%22NOD1%22%2C%22EIF4E3%22%2C%22ADGRE1%22%2C%22Altered%20group%22%2C%22Unaltered%20group%22%2C%22CD274%22%5D&comparison_subtab=survival&plots_horz_selection=%7B%22dataType%22%3A%22clinical_attribute%22%2C%22selectedDataSourceOption%22%3A%22AJCC_PATHOLOGIC_TUMOR_STAGE%22%7D&plots_vert_selection=%7B%22selectedGeneOption%22%3A29126%7D&plots_coloring_selection=%7B%22colorByCopyNumber%22%3A%22false%22%2C%22selectedOption%22%3A%221293_undefined%22%7D

 

 

Kind regards,

 

Yufei 

 

From: QATTAN, AMAL TALAT <aka...@kfshrc.edu.sa> 
Sent: Thursday, July 20, 2023 9:42 AM
To: SHI, YUFEI <yu...@kfshrc.edu.sa>
Subject: 20 July 2023# OS for (Col6a3) by using KM plotter & cBioportal 
Importance: High

 

Hi Dr.Yufei, I think its due to differences in datasets, sample sizes, statistical methods, data preprocessing, and other factors can all influence the outcomes of survival analysis. These variations can affect the significance of associations, the estimation of survival probabilities, and the calculation of p-values. The difference in the OS from Kaplan Meier plotter and cBioportal could be that these two platforms may have different datasets or sources of data, which could lead to variations in the results. Additionally, the algorithms or statistical methods used to calculate p-values might differ between the platforms, resulting in slightly different outcomes. Moreover, differences in sample sizes can also impact the results. With a larger sample size in Kaplan Meier plotter (n=7462), there might be more statistical power to detect significant associations or differences in survival outcomes compared to cBioportal's smaller sample size (n=497). Furthermore, variations in data preprocessing, quality control measures, or even the specific gene or molecular characteristics of the thyroid cancer samples in each database could contribute to the discrepancy. Each platform may have different inclusion criteria, patient demographics, or even time frames for data collection, which can influence the results as well. The reasons I mentioned here can potentially impact the results of overall survival.  It's important to consider all these factors when comparing results from different platforms or databases. I hope this helps…

 

 

 

From: SHI, YUFEI
Sent: Thursday, July 20, 2023 8:17 AM
To: QATTAN, AMAL TALAT
Subject: RE: 19 July 2023# Done WeTransfer +Pdf

 

Yes, this is what I got from the KM plotter, but I could not get similar results from cBioPortal?

 

From: QATTAN, AMAL TALAT <aka...@kfshrc.edu.sa> 
Sent: Thursday, July 20, 2023 8:14 AM
To: SHI, YUFEI <yu...@kfshrc.edu.sa>
Subject: RE: 19 July 2023# Done WeTransfer +Pdf

 

Good morning Dr.Yufei, It's strange that I received information yesterday about KM for breast cancer . However, please take a look at the attached PDF.

 

 

From: SHI, YUFEI
Sent: Thursday, July 20, 2023 8:08 AM
To: QATTAN, AMAL TALAT
Subject: RE: 19 July 2023# Done WeTransfer +Pdf

 

I am using thyroid cancer dataset from KM plotter (I think they use TCGA thyroid cancer dataset: n=502)

 

 

From: QATTAN, AMAL TALAT <aka...@kfshrc.edu.sa> 
Sent: Wednesday, July 19, 2023 7:34 PM
To: SHI, YUFEI <yu...@kfshrc.edu.sa>
Subject: RE: 19 July 2023# Done WeTransfer +Pdf
Importance: High

 

Hi Dr.Yufei, 

 The dataset/patient cohorts/ cancer types used is different between the two. cBioPortal is a comprehensive platform that has multiple cancer types and data from various cancer studies. On the other hand, KM plotter (Kaplan-Meier plotter) is designed for studying breast cancer. It focuses on analyzing the impact of gene levels on patient survival outcomes in breast cancer. KM plotter integrates gene expression data from thousands of breast cancer patients to generate Kaplan-Meier survival plots and how specific genes may influence overall survival or relapse-free survival in breast cancer patients.  The difference in OS outcomes you observed between cBioPortal and KM plotter might be because KM plotter focuses on breast cancer, whereas in cBioPortal the dataset was on Thyroid cancer.Consequently, the dataset/patient cohorts/ cancer types used is different, leading to different survival results.  Also, if you change the cancer type in cBioportal itself to BC instead of TC , the overall survival (OS) results will be the same as those in KM plotter. Please see also the following link to find the same results for OS similar to KM plotter for BC and cBioPortal for TC. For example, if you select the TCGA option and write your gene (Col6a3) in the search box, choose the TCGA dataset, and then select Breast Cancer as an example, it will take you to the next page. Click on the "survival" option on that page, and you will have the same results as those from KM plotter & cBioportal for BC. Similarly, if you go back and choose TC, it will show you with the same results for TC as the one from cBioportal.

https://ualcan.path.uab.edu/analysis.html

I hope this answers your question, clarifies the point, and helps make the difference you noticed between the two clear now.

 

From: SHI, YUFEI
Sent: Wednesday, July 19, 2023 5:31 PM
To: QATTAN, AMAL TALAT
Subject: RE: 19 July 2023# Done WeTransfer +Pdf

 

I am facing a problem using Kaplan-Meier Plotter and cBioPortal to predict survival using Col6a3 gene. I do not know which prediction is correct. Please see the link below and I would like to hear your feedback.

 

https://www.cbioportal.org/results/comparison?cancer_study_list=thca_tcga_pan_can_atlas_2018&Z_SCORE_THRESHOLD=2.0&RPPA_SCORE_THRESHOLD=2.0&profileFilter=rna_seq_v2_mrna_median_all_sample_ref_normal_Zscores&case_set_id=thca_tcga_pan_can_atlas_2018_all&gene_list=COL6A3&geneset_list=%20&tab_index=tab_visualize&Action=Submit&comparison_selectedGroups=%5B%22LBH%22%2C%22FNDC4%22%2C%22NOD1%22%2C%22EIF4E3%22%2C%22ADGRE1%22%2C%22Altered%20group%22%2C%22Unaltered%20group%22%2C%22CD274%22%5D&comparison_subtab=survival&plots_horz_selection=%7B%22dataType%22%3A%22clinical_attribute%22%2C%22selectedDataSourceOption%22%3A%22AJCC_PATHOLOGIC_TUMOR_STAGE%22%7D&plots_vert_selection=%7B%22selectedGeneOption%22%3A29126%7D&plots_coloring_selection=%7B%22colorByCopyNumber%22%3A%22false%22%2C%22selectedOption%22%3A%221293_undefined%22%7D

 

 

https://kmplot.com/analysis/index.php?p=service

 

From: QATTAN, AMAL TALAT <aka...@kfshrc.edu.sa> 
Sent: Wednesday, July 19, 2023 4:20 PM
To: SHI, YUFEI <yu...@kfshrc.edu.sa>
Subject: 19 July 2023# Done WeTransfer +Pdf
Importance: High

 

Dear Dr.Yufei, Please check your email and see the attachment Pdf. Let me know if you have any difficulties while downloading the folder from your KFSHRC email/account.

 

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[Schultz, Nikolaus]

Hi,

Do both tools use the same threshold to define over-expression? That may explain the differences. 

Niki.

On Apr 25, 2024, at 10:09 AM, 'SHI, YUFEI' via cBioPortal for Cancer Genomics Discussion Group <cbiop...@googlegroups.com> wrote:

Dear Niki:

 

Thank you for your prompt reply. The overall survival is still not significant after selection of over-expressed group although significant poor Disease-specific survival is observed. KM plotter does not calculate Disease-specific survival but shows significant poor overall survival. I would like to hear your comments.

 

Thank you,

Yufei

 

 <image004.png>

<image001.png>

<image003.jpg>

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[SHI, YUFEI]

Hello Niki:

 

I have a quick question about calculation of aneuploidy score. In the screen shot below, only altered group shows the score while unaltered group has no score shown?

 

[Schultz, Nikolaus]

Hi,

Can you please send a link to the query so that we can reproduce your finding?

Thanks.

Niki.

On Sep 9, 2024, at 4:54 AM, SHI, YUFEI <yu...@kfshrc.edu.sa> wrote:

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Hello Niki:

 

I have a quick question about calculation of aneuploidy score. In the screen shot below, only altered group shows the score while unaltered group has no score shown?

 

<image002.png>

[Schultz, Nikolaus]

Hi,

This looks like a bug / missing feature on our end. Since there are so many samples on the bottom line, the box is essentially the same size as that line and the summary therefore not available upon mouseover. We will try to come up with a fix to this. I apologize for the inconvenience. 

Niki.

On Sep 9, 2024, at 4:54 AM, 'SHI, YUFEI' via cBioPortal for Cancer Genomics Discussion Group <cbiop...@googlegroups.com> wrote:

Hello Niki:

 

I have a quick question about calculation of aneuploidy score. In the screen shot below, only altered group shows the score while unaltered group has no score shown?

 

<image002.png>

To view this discussion on the web visit https://groups.google.com/d/msgid/cbioportal/42c3748404ee4084805bd43c8bfcfc9d%40kfshrc.edu.sa.

[SHI, YUFEI]

Hi NiKi:

I have another enquiry about TERT promoter mutations. There are only 2 mutations shown in cBioportal in the Papillary Thyroid Carcinoma (TCGA, Cell 2014). https://www.cbioportal.org/results/mutations?cancer_study_list=thca_tcga_pub&tab_index=tab_visualize&case_set_id=thca_tcga_pub_all&Action=Submit&gene_list=TERT

TERT promoter mutations was documented in 36 (9.4%) of 384 informative tumors, with 27 (7.0%) C228T, 1 (0.3%) C228A and 8 (2.1%) C250T substitutions in the Cell paper. Are you able to add TERT promoter mutations in the cBioportal THCA database?

Best regards,
Yufei

[Schultz, Nikolaus]

Hu Yufei. We can look into this. Arusha, can your team please do this? Thank you!

Niki.

On Sep 22, 2024, at 8:01 AM, SHI, YUFEI <yu...@kfshrc.edu.sa> wrote:

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Hi NiKi:

I have another enquiry about TERT promoter mutations. There are only 2 mutations shown in cBioportal in the Papillary Thyroid Carcinoma (TCGA, Cell 2014). https://urldefense.com/v3/__https://www.cbioportal.org/results/mutations?cancer_study_list=thca_tcga_pub&tab_index=tab_visualize&case_set_id=thca_tcga_pub_all&Action=Submit&gene_list=TERT__;!!KVWo1iE!XsT59V6KdSZ-KdLqVfCqtBDzSOj0-q1YLDSin6byHJKUceAJrXu-vyNvOYKfZPQHyNGYh6dL6dd4Qjl-cQ$

TERT promoter mutations was documented in 36 (9.4%) of 384 informative tumors, with 27 (7.0%) C228T, 1 (0.3%) C228A and 8 (2.1%) C250T substitutions in the Cell paper. Are you able to add TERT promoter mutations in the cBioportal THCA database?

Best regards,
Yufei

-----Original Message-----
From: Schultz, Nikolaus <Schu...@mskcc.org> 
Sent: Wednesday, September 11, 2024 5:37 PM
To: SHI, YUFEI <yu...@kfshrc.edu.sa>
Cc: cbiop...@googlegroups.com; Satravada, Baby <Satr...@mskcc.org>
Subject: Re: [cbioportal] Reminder# cBioportal# OS for (Col6a3) by using cBioportal & KM plotter

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[Ramya Madupuri]

Hi Yufei,

The TERTp mutation status in the Thyroid Carcinoma study is captured in the clinical table (TERT Promoter Mutation attribute) due to the difference in the number of samples profiled for WES/WGS (496) and TERTp (384). Including them in the mutation table would result in incorrect altered percentage calculations. You can find more details at: https://github.com/cBioPortal/datahub/issues/154#issuecomment-1429952501.

Hope this helps!

Thanks,
Ramya

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[Schultz, Nikolaus]

Thanks Ramya!

I wonder if we can ad the mutations anyway and add a case list with the samples for which TERT promoter mutations are available? 

Niki

[Ramya Madupuri]

Hi Niki,

Sure, it seems we didn't have the exact sample list for TERTp. I'll look into it further and add them to the mutation table.

Thank you, 

Ramya

[SHI, YUFEI]

It will be helpful and avoid confusion to include TERT promoter mutation data in the mutation data file and oncoprint. For samples without TERT mutation data, you can simply marked as unprofiled. I also notice that TERT promoter mutation data were not provided in TCGA, GDC; TCGA, Firehose Legacy; and TCGA, PanCancer Atlas. Can you please let me know what is the difference among 4 papillary thyroid cancer datasets.

Thank you.

Sent from my iPhone

On 25 Sep 2024, at 9:40 AM, Schultz, Nikolaus <Schu...@mskcc.org> wrote:

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[Schultz, Nikolaus]

Hi Yufei,

The four different TCGA thyroid cancer data sets reflect slightly different versions and processing pipelines that have been run over the years. None of these officially included the TERT promoter mutations, as those were run separately. See more on this in our FAQ.

We can add the TERT promoter mutations to the Cell paper study. We can add a case list for TERT profiled samples, but have no additional options to indicate in any analyses which samples were sequenced for TERT promoter mutations. 

Niki.

<Mail Attachment.eml>

[SHI, YUFEI]

Hello Niki:

Now I can see Tert promoter mutation data on OncoPrint of TCGA, Cell 2014 dataset. I also notice significantly higher reported death rate in that dataset (91 death). By comparing with other 3 datasets (PanCancer Atlas, Firehose Legacy, and DGC) which have only 16 reported death. To my surprise, many patients reported as DECEASED in Cell 2014 dataset are reported as Living in other 3 dataset. Please see attached excel sheet for your information and comments.

Best regards,

Yufei

-----Original Message-----
From: Schultz, Nikolaus <Schu...@mskcc.org>
Sent: Friday, September 27, 2024 2:37 PM
To: SHI, YUFEI <yu...@kfshrc.edu.sa>
Cc: Ramya Madupuri <ramyama...@gmail.com>; cbiop...@googlegroups.com; Satravada, Baby <Satr...@mskcc.org>
Subject: Re: [cbioportal] Reminder# cBioportal# OS for (Col6a3) by using cBioportal & KM plotter

[Ramya Madupuri]

Hi Yufei,

Thank you for bringing this to our attention. We have identified the issue and are working on a fix. I will follow up once the update is live in the portal.

Thanks,

Ramya

[Ramya Madupuri]

Hi Yufei,

Just following up - the data has been corrected in the portal.

Thanks,

Ramya

[SHI, YUFEI]

Dear Niki:

I have not received your reply I sent last week regarding survival data on TCGA-THCA Cell 2014 database. If you did not receive it, I can resend it again.

Kind regards,

Yufei

-----Original Message-----
From: Schultz, Nikolaus <Schu...@mskcc.org>
Sent: Friday, September 27, 2024 2:37 PM
To: SHI, YUFEI <yu...@kfshrc.edu.sa>
Cc: Ramya Madupuri <ramyama...@gmail.com>; cbiop...@googlegroups.com; Satravada, Baby <Satr...@mskcc.org>
Subject: Re: [cbioportal] Reminder# cBioportal# OS for (Col6a3) by using cBioportal & KM plotter

[Schultz, Nikolaus]

Hi,

Yes, please resend … I am not sure anymore which question we have not answered.

N

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[SHI, YUFEI]

Hello Niki:

Did you receive the email I resent yesterday?

Sent from my iPad

> On 28 Oct 2024, at 6:38 PM, Schultz, Nikolaus <Schu...@mskcc.org> wrote:
>
> CAUTION: This email message is received from an external entity. Exercise caution, and please do not reply, disclose any information, click on any link, or browse attachments unless you are absolutely sure of the sender.

[Schultz, Nikolaus]

Hi Yufei,

I think it is easier if you send all correspondence to this email thread and keep the Google Group cc’d, that way others can follow along and weigh in.

I think you are referring to your previous question about death events in the TCGA thyroid cancer cohort. Your spreadsheet lists 91 patients for the 2014 Cell paper cohort, but the matching cBioPortal cohort shows 14 events. See the screenshot below.

Please double-check and let us know if you still see discrepancies.

Niki.

 On Oct 30, 2024, at 2:41 AM, SHI, YUFEI <yu...@kfshrc.edu.sa> wrote:

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Hello Niki:

Did you receive the email I resent yesterday?

Sent from my iPad

> On 28 Oct 2024, at 6:38 PM, Schultz, Nikolaus <Schu...@mskcc.org> wrote:
> 
> CAUTION: This email message is received from an external entity. Exercise caution, and please do not reply, disclose any information, click on any link, or browse attachments unless you are absolutely sure of the sender.
> 
> Hi,
> 
> Yes, please resend … I am not sure anymore which question we have not answered.
> 
> N
> 
> 
>> On Oct 28, 2024, at 1:56 AM, 'SHI, YUFEI' via cBioPortal for Cancer Genomics Discussion Group <cbiop...@googlegroups.com> wrote:
>> 
>> Dear Niki:
>> 
>> I have not received your reply I sent last week regarding survival data on TCGA-THCA Cell 2014 database. If you did not receive it, I can resend it again.
>> 
>> Kind regards,
>> Yufei
>> 
>> -----Original Message-----
>> From: Schultz, Nikolaus <Schu...@mskcc.org>
>> Sent: Friday, September 27, 2024 2:37 PM
>> To: SHI, YUFEI <yu...@kfshrc.edu.sa>
>> Cc: Ramya Madupuri <ramyama...@gmail.com>; cbiop...@googlegroups.com; Satravada, Baby <Satr...@mskcc.org>
>> Subject: Re: [cbioportal] Reminder# cBioportal# OS for (Col6a3) by using cBioportal & KM plotter
>> 
>> CAUTION: This email message is received from an external entity. Exercise caution, and please do not reply, disclose any information, click on any link, or browse attachments unless you are absolutely sure of the sender.
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[SHI, YUFEI]

My concern is that the same patients recorded as death in Cell 2014 data set are recorded as living in other 3 datasets. Which one is correct? The patients cannot be both dead and living at the same time? 

Sent from my iPhone

[Schultz, Nikolaus]

I did some quick checking and see matching information at least between the Cell and GDC cohorts. See example below.

The spreadsheet you sent earlier showed 91 deaths in the Cell cohort … where did you get that information from? I think that is where your discrepancy is coming from.

On Oct 30, 2024, at 10:12 AM, SHI, YUFEI <yu...@kfshrc.edu.sa> wrote:

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My concern is that the same patients recorded as death in Cell 2014 data set are recorded as living in other 3 datasets. Which one is correct? The patients cannot be both dead and living at the same time? 

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On 30 Oct 2024, at 4:20 PM, Schultz, Nikolaus <Schu...@mskcc.org> wrote:



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Hi Yufei,

I think it is easier if you send all correspondence to this email thread and keep the Google Group cc’d, that way others can follow along and weigh in.

I think you are referring to your previous question about death events in the TCGA thyroid cancer cohort. Your spreadsheet lists 91 patients for the 2014 Cell paper cohort, but the matching cBioPortal cohort shows 14 events. See the screenshot below.

Please double-check and let us know if you still see discrepancies.

Niki.

[Ramya Madupuri]

Hi Niki, Yufei,

It seems my last two responses got mixed with other questions in the thread. For the Survival status of THCA Cell 2014, a few patients without survival time were incorrectly labeled as Deceased and it was corrected on our end. This discrepancy should no longer appear in the portal.

Yufei, can you please check the portal again. I have also attached the survival data comparison across the four datasets for your reference.

Thanks,
Ramya

[SHI, YUFEI]

I re-checked the OncoPrint of Cell 2014. Now the total death is 14 (not 91 anymore) and in line with other three databases. This is due to computer/system glitch? Anyway, I am happy to see consistent death rate.