Title: Netrin-1-CD146 and S100A9-CD146 are associated with early stage of lymph node
metastasis in colorectal cancer
Version: 1 Date: 15 Jul 2024
Reviewer's report:
In this manuscript, the authors presented netrin-1-CD146 and S100A9-CD146 were associated
with early stage of lymph node metastasis in colorectal cancer (CRC), providing a novel
therapeutic target for lymphatic metastasis. Their approach that focused on sentinel lymph
nodes is interesting, but I would suggest that additional information is required to make their
conclusions more reliable.
(1) The authors demonstrated that netrin-1 highly expressed in CRC patients with lymphatic
metastasis, especially N1a+1b, compared to patients with N0 and N2. They also showed positive
correlations between netrin-1/CD146 and CD146/S100A9 and mentioned that netrin-1/CD146
and CD146/S100A9 axis might be related to lymph metastasis in CRC. They cited references
and described that these genes have been shown to be upregulated in various cancers, including
CRC, and involved in malignant behavior. However, no differences were observed in CD146
and S100A9 expression levels themselves in their results. Also, netrin-1 and CD146 levels were
not associated with CRC stage, survival, and recurrence.
As they mentioned, netrin-1 could be a potential therapeutic target to prevent the initiation of
metastasis, but I would say that only their present results may be scant to say that these axes
are related and important for CRC. Please provide some results and comments that support the
above.
(2) In their manuscript and schematic (Supplementary Fig.1), netrin-1 does not seem to play
a key role in the sentinel lymph nodes, but CD146 might be important to drive lymphatic
metastasis in the nodes. Please stain the sentinel lymph node specimens with CD146 and provide
results about expression levels and correlations like Table 5 and 6.
(3) The authors showed that high netrin-1 expression was observed in CRC patients with N1 and
could be related with lymph node metastasis. Please add lymphatic vessel invasion and venous
invasion status based on the staining results in Table 2.
(4) The authors found netrin-1 expression was high particularly in patients with N1. Is it possible
that re-analysis by each N stage would change the S100 A8/A9 results (Table 5)?
(5) How did the authors define and collect the sentinel lymph nodes? Did they use indocyanine
green or something to detect lymph flow and then use the nearest node? Please mention the
detail in method.
(6) I guess that “revealed a possible new mechanism for vascular metastasis” in abstract may be
overstated with their present results. Please modify to appropriate text.
(7) The authors stated in abstract that “The level of netrin-1 protein was positively correlated
with CD146 protein (r=0.414, P=0.001, 60 samples; r=0.430, P=0.02, 29 samples)”. However,
it would be difficult to understand the meaning of those samples from the abstract alone.
Title: Netrin-1-CD146 and S100A9-CD146 are associated with early stage of lymph node
metastasis in colorectal cancer
Version: 1 Date: 15 Jul 2024
Reviewer's report:
In this manuscript, the authors presented netrin-1-CD146 and S100A9-CD146 were associated
with early stage of lymph node metastasis in colorectal cancer (CRC), providing a novel
therapeutic target for lymphatic metastasis. Their approach that focused on sentinel lymph
nodes is interesting, but I would suggest that additional information is required to make their
conclusions more reliable.
(1) The authors demonstrated that netrin-1 highly expressed in CRC patients with lymphatic
metastasis, especially N1a+1b, compared to patients with N0 and N2. They also showed positive
correlations between netrin-1/CD146 and CD146/S100A9 and mentioned that netrin-1/CD146
and CD146/S100A9 axis might be related to lymph metastasis in CRC. They cited references
and described that these genes have been shown to be upregulated in various cancers, including
CRC, and involved in malignant behavior. However, no differences were observed in CD146
and S100A9 expression levels themselves in their results. Also, netrin-1 and CD146 levels were
not associated with CRC stage, survival, and recurrence.
As they mentioned, netrin-1 could be a potential therapeutic target to prevent the initiation of
metastasis, but I would say that only their present results may be scant to say that these axes
are related and important for CRC. Please provide some results and comments that support the
above.
(2) In their manuscript and schematic (Supplementary Fig.1), netrin-1 does not seem to play
a key role in the sentinel lymph nodes, but CD146 might be important to drive lymphatic
metastasis in the nodes. Please stain the sentinel lymph node specimens with CD146 and provide
results about expression levels and correlations like Table 5 and 6.
(3) The authors showed that high netrin-1 expression was observed in CRC patients with N1 and
could be related with lymph node metastasis. Please add lymphatic vessel invasion and venous
invasion status based on the staining results in Table 2.
(4) The authors found netrin-1 expression was high particularly in patients with N1. Is it possible
that re-analysis by each N stage would change the S100 A8/A9 results (Table 5)?
(5) How did the authors define and collect the sentinel lymph nodes? Did they use indocyanine
green or something to detect lymph flow and then use the nearest node? Please mention the
detail in method.
(6) I guess that “revealed a possible new mechanism for vascular metastasis” in abstract may be
overstated with their present results. Please modify to appropriate text.
(7) The authors stated in abstract that “The level of netrin-1 protein was positively correlated
with CD146 protein (r=0.414, P=0.001, 60 samples; r=0.430, P=0.02, 29 samples)”. However,
it would be difficult to understand the meaning of those samples from the abstract alone.
Please review this paper.
user
Title: Netrin-1-CD146 and S100A9-CD146 are associated with early stage of lymph node
metastasis in colorectal cancer
Version: 1 Date: 15 Jul 2024
Reviewer's report:
In this manuscript, the authors presented netrin-1-CD146 and S100A9-CD146 were associated
with early stage of lymph node metastasis in colorectal cancer (CRC), providing a novel
therapeutic target for lymphatic metastasis. Their approach that focused on sentinel lymph
nodes is interesting, but I would suggest that additional information is required to make their
conclusions more reliable.
(1) The authors demonstrated that netrin-1 highly expressed in CRC patients with lymphatic
metastasis, especially N1a+1b, compared to patients with N0 and N2. They also showed positive
correlations between netrin-1/CD146 and CD146/S100A9 and mentioned that netrin-1/CD146
and CD146/S100A9 axis might be related to lymph metastasis in CRC. They cited references
and described that these genes have been shown to be upregulated in various cancers, including
CRC, and involved in malignant behavior. However, no differences were observed in CD146
and S100A9 expression levels themselves in their results. Also, netrin-1 and CD146 levels were
not associated with CRC stage, survival, and recurrence.
As they mentioned, netrin-1 could be a potential therapeutic target to prevent the initiation of
metastasis, but I would say that only their present results may be scant to say that these axes
are related and important for CRC. Please provide some results and comments that support the
above.
(2) In their manuscript and schematic (Supplementary Fig.1), netrin-1 does not seem to play
a key role in the sentinel lymph nodes, but CD146 might be important to drive lymphatic
metastasis in the nodes. Please stain the sentinel lymph node specimens with CD146 and provide
results about expression levels and correlations like Table 5 and 6.
(3) The authors showed that high netrin-1 expression was observed in CRC patients with N1 and
could be related with lymph node metastasis. Please add lymphatic vessel invasion and venous
invasion status based on the staining results in Table 2.
(4) The authors found netrin-1 expression was high particularly in patients with N1. Is it possible
that re-analysis by each N stage would change the S100 A8/A9 results (Table 5)?
(5) How did the authors define and collect the sentinel lymph nodes? Did they use indocyanine
green or something to detect lymph flow and then use the nearest node? Please mention the
detail in method.
(6) I guess that “revealed a possible new mechanism for vascular metastasis” in abstract may be
overstated with their present results. Please modify to appropriate text.
(7) The authors stated in abstract that “The level of netrin-1 protein was positively correlated
with CD146 protein (r=0.414, P=0.001, 60 samples; r=0.430, P=0.02, 29 samples)”. However,
it would be difficult to understand the meaning of those samples from the abstract alone.
assistant