Round 1

Reviewer 1 Report

Interesting and well written article

Author Response

Reviewer 1

Reviewer’s comment:

Interesting and well written article

Authors’ response:

Thank you for your comment.

Reviewer 2 Report

This study clearly showed negative results of TPS antigen in the early diagnosis of pancreatic cancer.

1. There are two cohorts in this study but it is difficult to understand the prediagnostic and diagnostic cohorts. Can you also add a flow chart of the diagnostic cohort, too? And summarize the data showing  how two cohorts were evaluated in Discussion.
2. Can you provide data of TPS antigen according to the PDAC stage?
3. Was there any validation for measurement of TPS antigen in the old sample (up to 18.8 yrs)?

Author Response

Reviewer 2

Reviewer’s comment:

This study clearly showed negative results of TPS antigen in the early diagnosis of pancreatic cancer.

1. There are two cohorts in this study but it is difficult to understand the prediagnostic and diagnostic cohorts. Can you also add a flow chart of the diagnostic cohort, too? And summarize the data showing  how two cohorts were evaluated in Discussion.

Authors’ response:

Thank you for this valuable comment. We have now included a flowchart showing inclusion/exclusion of samples in the diagnostic cohort as well (Fig.1B). We also added a sentence at the end of the first paragraph in the Discussion section.

Reviewer’s comment:

2. Can you provide data of TPS antigen according to the PDAC stage?

Authors’ response:

Thank you for your suggestion, a boxplot figure is now included in the manuscript showing TPS levels according to PDAC stage (Figure 3). We also describe the statistics performed in Statistical analyses section and added one sentence in the Discussion section.

Reviewer’s comment:

3. Was there any validation for measurement of TPS antigen in the old sample (up to 18.8 yrs)?

Authors’ response:

Since we did not detect any deviating TPS levels in the pre-diagnostic samples, we did not perform any validation in pre-diagnostic samples. These samples have been kept unthawed in -80C freezers and previous validations have shown high sample quality.

Reviewer 3 Report

The authors investigated whether TPS holds potential as an early circulating biomarker of PDAC. In the results, TPS levels were increased at PDAC diagnosis, but this increase occurred late and was not observed in pre-diagnostic PDAC samples. Unfortunately, these conclusions are not meaningful in clinical situations, and I do not recommend to be published in Cancers.

Author Response

Reviewer 3

Reviewer’s comment:

The authors investigated whether TPS holds potential as an early circulating biomarker of PDAC. In the results, TPS levels were increased at PDAC diagnosis, but this increase occurred late and was not observed in pre-diagnostic PDAC samples. Unfortunately, these conclusions are not meaningful in clinical situations, and I do not recommend to be published in Cancers.

Authors’ response:

We are sorry to hear that the reviewer does not find our paper suitable for publication in Cancers. The aim of our study was to determine the potential of TPS as an early circulating biomarker in pancreatic cancer by assessing the levels in samples taken pre-diagnostically. Our finding in the pre-diagnostic cohort is negative, still we consider our results important to be shared in the research field. Furthermore, we believe our paper is suitable for publication in Cancers according to the journal’s aims (“we accept studies showing meaningful but negative results”) and scope (“We publish high-quality articles including basic, translational, and clinical studies on all tumor types”).

Round 2

Reviewer 2 Report

The authors have revised the paper appropriately and I have no further comments.

Reviewer 3 Report

The authors investigated whether TPS holds potential as an early circulating biomarker of PDAC. In the results, TPS levels were increased at PDAC diagnosis, but this increase occurred late and was not observed in pre-diagnostic PDAC samples. Unfortunately, these conclusions are not meaningful in clinical situations, and I do not recommend to be published in Cancers, as I suggested in the previous review.