Title: THSD7A as a novel prognostic factor for colorectal carcinoma
Version: 1 Date: 13 Feb 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
The clinical implications of THSD7A expression in CRC prognosis and treatment strategies
should be clearly stated. The study should discuss how THSD7A expression could be integrated
into current prognostic models and whether it has potential as a therapeutic target or a biomarker
for patient stratification. A more thorough background is needed in the introduction to justify
the focus on THSD7A in CRC. The biological role of THSD7A in cancer should be expanded,
particularly its function in CRC angiogenesis, metastasis, and tumor progression. Additionally, a
comparison to other angiogenesis-related biomarkers would help contextualize its significance.
The patient selection criteria and exclusion criteria in the study design need further clarification.
It should be explicitly stated why patients with missing data or inadequate tissue were
excluded and whether this introduced any selection bias that could affect the study results. The
immunohistochemistry scoring criteria for THSD7A positivity are not standard, and the cutoff
point (#1% expression) is relatively low. A justification for this threshold should be provided,
citing relevant literature that supports this cutoff. Alternatively, a sensitivity analysis using
different cutoff values could strengthen the validity of the chosen threshold.
The Kaplan-Meier curves (Fig. 2) are missing in the provided document and should be ensured
to be included. All figures must be properly labeled with appropriate legends, and log-rank
test values should be mentioned in the text for clarity. In the multivariate analysis, the hazard
ratios (HRs) are provided, but the confidence intervals (CIs) are quite wide, suggesting potential
overfitting. It would be beneficial to check the proportional hazards assumption for Cox
regression. If sample size is a limitation, bootstrapping methods could be used to obtain more
robust estimates.
The discussion should provide a mechanistic hypothesis explaining why THSD7A behaves
differently in various cancers. Since THSD7A appears to be beneficial in some cancers but
detrimental in others, it is important to explore whether these differences are dependent
on the tumor microenvironment or specific molecular interactions unique to each cancer
type. The study limitations are only briefly mentioned and should be expanded. Potential
biases, particularly those introduced by the retrospective nature of the study, the small sample
size, and the lack of functional validation through in vitro experiments, should be explicitly
acknowledged.
Several key references on THSD7A research, particularly functional studies, appear to be
missing from the references section. Recent studies from 2022 to 2024 that further validate or
contrast the study’s findings should be included to ensure a comprehensive literature review and
strengthen the discussion
Title: THSD7A as a novel prognostic factor for colorectal carcinoma
Version: 1 Date: 13 Feb 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
The clinical implications of THSD7A expression in CRC prognosis and treatment strategies
should be clearly stated. The study should discuss how THSD7A expression could be integrated
into current prognostic models and whether it has potential as a therapeutic target or a biomarker
for patient stratification. A more thorough background is needed in the introduction to justify
the focus on THSD7A in CRC. The biological role of THSD7A in cancer should be expanded,
particularly its function in CRC angiogenesis, metastasis, and tumor progression. Additionally, a
comparison to other angiogenesis-related biomarkers would help contextualize its significance.
The patient selection criteria and exclusion criteria in the study design need further clarification.
It should be explicitly stated why patients with missing data or inadequate tissue were
excluded and whether this introduced any selection bias that could affect the study results. The
immunohistochemistry scoring criteria for THSD7A positivity are not standard, and the cutoff
point (#1% expression) is relatively low. A justification for this threshold should be provided,
citing relevant literature that supports this cutoff. Alternatively, a sensitivity analysis using
different cutoff values could strengthen the validity of the chosen threshold.
The Kaplan-Meier curves (Fig. 2) are missing in the provided document and should be ensured
to be included. All figures must be properly labeled with appropriate legends, and log-rank
test values should be mentioned in the text for clarity. In the multivariate analysis, the hazard
ratios (HRs) are provided, but the confidence intervals (CIs) are quite wide, suggesting potential
overfitting. It would be beneficial to check the proportional hazards assumption for Cox
regression. If sample size is a limitation, bootstrapping methods could be used to obtain more
robust estimates.
The discussion should provide a mechanistic hypothesis explaining why THSD7A behaves
differently in various cancers. Since THSD7A appears to be beneficial in some cancers but
detrimental in others, it is important to explore whether these differences are dependent
on the tumor microenvironment or specific molecular interactions unique to each cancer
type. The study limitations are only briefly mentioned and should be expanded. Potential
biases, particularly those introduced by the retrospective nature of the study, the small sample
size, and the lack of functional validation through in vitro experiments, should be explicitly
acknowledged.
Several key references on THSD7A research, particularly functional studies, appear to be
missing from the references section. Recent studies from 2022 to 2024 that further validate or
contrast the study’s findings should be included to ensure a comprehensive literature review and
strengthen the discussion
Please review this paper.
user
Title: THSD7A as a novel prognostic factor for colorectal carcinoma
Version: 1 Date: 13 Feb 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
The clinical implications of THSD7A expression in CRC prognosis and treatment strategies
should be clearly stated. The study should discuss how THSD7A expression could be integrated
into current prognostic models and whether it has potential as a therapeutic target or a biomarker
for patient stratification. A more thorough background is needed in the introduction to justify
the focus on THSD7A in CRC. The biological role of THSD7A in cancer should be expanded,
particularly its function in CRC angiogenesis, metastasis, and tumor progression. Additionally, a
comparison to other angiogenesis-related biomarkers would help contextualize its significance.
The patient selection criteria and exclusion criteria in the study design need further clarification.
It should be explicitly stated why patients with missing data or inadequate tissue were
excluded and whether this introduced any selection bias that could affect the study results. The
immunohistochemistry scoring criteria for THSD7A positivity are not standard, and the cutoff
point (#1% expression) is relatively low. A justification for this threshold should be provided,
citing relevant literature that supports this cutoff. Alternatively, a sensitivity analysis using
different cutoff values could strengthen the validity of the chosen threshold.
The Kaplan-Meier curves (Fig. 2) are missing in the provided document and should be ensured
to be included. All figures must be properly labeled with appropriate legends, and log-rank
test values should be mentioned in the text for clarity. In the multivariate analysis, the hazard
ratios (HRs) are provided, but the confidence intervals (CIs) are quite wide, suggesting potential
overfitting. It would be beneficial to check the proportional hazards assumption for Cox
regression. If sample size is a limitation, bootstrapping methods could be used to obtain more
robust estimates.
The discussion should provide a mechanistic hypothesis explaining why THSD7A behaves
differently in various cancers. Since THSD7A appears to be beneficial in some cancers but
detrimental in others, it is important to explore whether these differences are dependent
on the tumor microenvironment or specific molecular interactions unique to each cancer
type. The study limitations are only briefly mentioned and should be expanded. Potential
biases, particularly those introduced by the retrospective nature of the study, the small sample
size, and the lack of functional validation through in vitro experiments, should be explicitly
acknowledged.
Several key references on THSD7A research, particularly functional studies, appear to be
missing from the references section. Recent studies from 2022 to 2024 that further validate or
contrast the study’s findings should be included to ensure a comprehensive literature review and
strengthen the discussion
assistant