Title: Platelet-to-High-Density Lipoprotein Ratio (PHR) as a Predictive Biomarker for
Gastrointestinal Cancers: Evidence from NHANES
Version: 1 Date: 18 Feb 2025
Reviewer's report:
This manuscript by Tong et al. presents an interesting and potentially important study on the
role of the platelet-to-high-density lipoprotein ratio (PHR) as a biomarker for gastrointestinal
(GI) cancers. Overall, the study has several strengths but also some areas that require further
clarification and improvement.
1. Highlights and Innovation of This Manuscript
This study comprehensively evaluates the association between platelet-to-high-density
lipoprotein ratio (PHR) and gastrointestinal (GI) cancer risk using a large-scale and nationally
representative dataset from NHANES 2010 - 2018. It finds that elevated PHR is independently
associated with an increased risk of GI cancers and shows a significant dose-response
relationship with two critical inflection points at PHR values of 3.2 and 4.5. This is a novel
and important finding that highlights the potential of PHR as a biomarker for GI cancer risk
stratification.
Meanwhile, the study conducts subgroup analyses and reveals that the association between PHR
and GI cancer risk is stronger among older adults, males, and obese individuals, and there are
significant effect modifications by age and BMI. These subgroup analyses provide valuable
insights into the heterogeneity of the relationship and help to identify high-risk populations more
precisely .
The whole paper discusses the biological mechanisms underlying the association between
PHR and GI cancers, integrating the roles of platelets in promoting tumorigenesis and
HDL-C in suppressing it. This mechanistic exploration enhances the understanding of the
pathophysiological basis of the observed associations .
2. Recommendations for Revision
(1) Although you have adjusted for a wide range of covariates, there are still other potential
confounders that might influence the results. Dietary patterns, genetic predispositions, and
detailed tumor characteristics should be incorporated into future research. Please provide more
details on the potential impact of excluded participants, the methods for collecting covariate
data, and the statistical analysis software and algorithms used.
(2)  Although the current sample size is relatively large, further stratification by specific GI
cancer subtypes would yield more detailed insights.  Analyze the data separately for gastric,
colorectal, and esophageal cancers to determine if there are subtype-specific differences in the
relationship between PHR and cancer risk. This could involve conducting subgroup analyses
for each subtype and reporting the results separately.  Please avoid overinterpreting subgroup
analysis results and provide more in-depth discussions on the reasons for differences, and discuss
the limitations more thoroughly and suggest specific ways to address them in future research.
Overall, this manuscript presents a well-conducted study with potentially important findings.
With some improvements in the areas mentioned above, it has the potential to make a significant
contribution to the field of cancer biomarker research.
Title: Platelet-to-High-Density Lipoprotein Ratio (PHR) as a Predictive Biomarker for
Gastrointestinal Cancers: Evidence from NHANES
Version: 1 Date: 18 Feb 2025
Reviewer's report:
This manuscript by Tong et al. presents an interesting and potentially important study on the
role of the platelet-to-high-density lipoprotein ratio (PHR) as a biomarker for gastrointestinal
(GI) cancers. Overall, the study has several strengths but also some areas that require further
clarification and improvement.
1. Highlights and Innovation of This Manuscript
This study comprehensively evaluates the association between platelet-to-high-density
lipoprotein ratio (PHR) and gastrointestinal (GI) cancer risk using a large-scale and nationally
representative dataset from NHANES 2010 - 2018. It finds that elevated PHR is independently
associated with an increased risk of GI cancers and shows a significant dose-response
relationship with two critical inflection points at PHR values of 3.2 and 4.5. This is a novel
and important finding that highlights the potential of PHR as a biomarker for GI cancer risk
stratification.
Meanwhile, the study conducts subgroup analyses and reveals that the association between PHR
and GI cancer risk is stronger among older adults, males, and obese individuals, and there are
significant effect modifications by age and BMI. These subgroup analyses provide valuable
insights into the heterogeneity of the relationship and help to identify high-risk populations more
precisely .
The whole paper discusses the biological mechanisms underlying the association between
PHR and GI cancers, integrating the roles of platelets in promoting tumorigenesis and
HDL-C in suppressing it. This mechanistic exploration enhances the understanding of the
pathophysiological basis of the observed associations .
2. Recommendations for Revision
(1) Although you have adjusted for a wide range of covariates, there are still other potential
confounders that might influence the results. Dietary patterns, genetic predispositions, and
detailed tumor characteristics should be incorporated into future research. Please provide more
details on the potential impact of excluded participants, the methods for collecting covariate
data, and the statistical analysis software and algorithms used.
(2)  Although the current sample size is relatively large, further stratification by specific GI
cancer subtypes would yield more detailed insights.  Analyze the data separately for gastric,
colorectal, and esophageal cancers to determine if there are subtype-specific differences in the
relationship between PHR and cancer risk. This could involve conducting subgroup analyses
for each subtype and reporting the results separately.  Please avoid overinterpreting subgroup
analysis results and provide more in-depth discussions on the reasons for differences, and discuss
the limitations more thoroughly and suggest specific ways to address them in future research.
Overall, this manuscript presents a well-conducted study with potentially important findings.
With some improvements in the areas mentioned above, it has the potential to make a significant
contribution to the field of cancer biomarker research.
Please review this paper.
user
Title: Platelet-to-High-Density Lipoprotein Ratio (PHR) as a Predictive Biomarker for
Gastrointestinal Cancers: Evidence from NHANES
Version: 1 Date: 18 Feb 2025
Reviewer's report:
This manuscript by Tong et al. presents an interesting and potentially important study on the
role of the platelet-to-high-density lipoprotein ratio (PHR) as a biomarker for gastrointestinal
(GI) cancers. Overall, the study has several strengths but also some areas that require further
clarification and improvement.
1. Highlights and Innovation of This Manuscript
This study comprehensively evaluates the association between platelet-to-high-density
lipoprotein ratio (PHR) and gastrointestinal (GI) cancer risk using a large-scale and nationally
representative dataset from NHANES 2010 - 2018. It finds that elevated PHR is independently
associated with an increased risk of GI cancers and shows a significant dose-response
relationship with two critical inflection points at PHR values of 3.2 and 4.5. This is a novel
and important finding that highlights the potential of PHR as a biomarker for GI cancer risk
stratification.
Meanwhile, the study conducts subgroup analyses and reveals that the association between PHR
and GI cancer risk is stronger among older adults, males, and obese individuals, and there are
significant effect modifications by age and BMI. These subgroup analyses provide valuable
insights into the heterogeneity of the relationship and help to identify high-risk populations more
precisely .
The whole paper discusses the biological mechanisms underlying the association between
PHR and GI cancers, integrating the roles of platelets in promoting tumorigenesis and
HDL-C in suppressing it. This mechanistic exploration enhances the understanding of the
pathophysiological basis of the observed associations .
2. Recommendations for Revision
(1) Although you have adjusted for a wide range of covariates, there are still other potential
confounders that might influence the results. Dietary patterns, genetic predispositions, and
detailed tumor characteristics should be incorporated into future research. Please provide more
details on the potential impact of excluded participants, the methods for collecting covariate
data, and the statistical analysis software and algorithms used.
(2)  Although the current sample size is relatively large, further stratification by specific GI
cancer subtypes would yield more detailed insights.  Analyze the data separately for gastric,
colorectal, and esophageal cancers to determine if there are subtype-specific differences in the
relationship between PHR and cancer risk. This could involve conducting subgroup analyses
for each subtype and reporting the results separately.  Please avoid overinterpreting subgroup
analysis results and provide more in-depth discussions on the reasons for differences, and discuss
the limitations more thoroughly and suggest specific ways to address them in future research.
Overall, this manuscript presents a well-conducted study with potentially important findings.
With some improvements in the areas mentioned above, it has the potential to make a significant
contribution to the field of cancer biomarker research.
assistant