Review for 10.1186/s12876-023-02824-1 (2023)

Title: Prognostic and biological function value of OSBPL3 in colorectal cancer analyzed by
Multi-Omic data analysis
Version: 4 Date: 15 May 2023
Reviewer's report:
The authors adequately responded to the reviewers' points without logical fallacies, and the
additional data were scientifically interesting.
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The authors analyzed and validated the OSBPL3 in a cohort study and found a correlation
with clinical prognostic values. The results of this study contributed to the advancement of
treatment of CRC and were very valuable. I think the paper is well organized, with no excesses
or deficiencies in the construction of the research design, the statistical treatment of the results,
and the conclusions drawn from the results. I read it with great interest.
I have the following comments.
Minor points
1. No explanation of abbreviations in Fig. 1 (e.g. BLCA, BRCA, CESC...)
RE: We apologize for our mistake. Based on your suggestion, we have added the full form of
the abbreviation in ‘Differential expression analysis of OSBPL3’ section as follows: OSBPL3
was differentially expressed in 13 tumors (bladder cancer (BLCA), cervical cancer (CESC),
colon adenocarcinoma (COAD), esophageal carcinoma (ESCA), head and neck squamous cell
carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma
(LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), pancreatic
adenocarcinoma (PAAD), rectum adenocarcinoma (READ), stomach adenocarcinoma (STAD),
and thyroid carcinoma (THCA)) with P < 0.01 (Figure 1A).
2. In Fig. 1, OSBPL3 was conversely decreased in KIRC and PRAD. No discussion derived
from these comparisons.
RE: Thank you for your comment. The results of Figure 1A show that OSBPL3 is lowly
expressed in tumor tissues of KIRC and PRAD, while highly expressed in the other 13 types
of cancer, indicating that OSBPL3 plays an important role in tumorigenesis. The main focus of
this study is to explore the prognostic value of OSBPL3 in CRC, so the analysis of pan-cancer is
supplementary rather than the main content of the study. By placing the differential expression
analysis of OSBPL3 in 15 cancer tissues at the beginning of the analysis, we not only highlight
the importance of OSBPL3, but also lay a theoretical foundation for our subsequent analysis.
3. In Fig. 7, the data was presented without any explanation of the relationship between the
function of OSBPL3 and the regulatory mechanism of drug resistance, which seemed abrupt.
Although the data is clinically significant, the significance of presenting the data is not clear.
In addition, the results were at odds with the correlation with prognosis shown in previous
experiments.
RE: We apologize for our negligence. This part of the study mainly focuses on selecting potential
therapeutic drugs for CRC patients based on the expression levels of OSBPL3. According to
your research, we have added the research purpose in ‘Drug sensitivity analysis’ section of
the results as follows: ‘To find the potential therapeutic drugs for patients in the high and low
expression groups of OSBPL3, we performed a drug sensitivity analysis.’The results show that
there were significant differences in the IC50 values of methotrexate, melphalan, fluorouracil,
pipobroman, mitomycin, tfdu, and cisplatin between the high and low expression groups of
OSBPL3, and the IC50 values of the high expression group were lower. IC50 (half maximal
inhibitory concentration) refers to the half-inhibitory concentration of the measured antagonist,
which indicates the sensitivity of a drug or substance (inhibitor) in inhibiting some biological
processes (or half the amount of certain substances included in this process), reflecting the
sensitivity of the drug. Therefore, the high expression group of OSBPL3 is more sensitive to the
above drugs, which means that the treatment outcome is better in the high expression group, so
this analysis result is meaningful. In the previous prognostic analysis, the survival curve showed
that OSBPL3 was significantly correlated with OS, DSS, DFS, and PFS of CRC patients, and the
higher the expression of OSBPL3, the worse the prognosis of CRC patients, which is consistent
with the report in PMID: 34308980. The poor prognosis of the high expression group of OSBPL3
and their higher sensitivity to the above 7 drugs are not contradictory, but these results may
provide a new perspective for the prognosis and treatment of CRC.
4. In “discussion” line 329, “However, these results indicated the expression of OSBPL3 had
changed in CRC”. I think this is an important point: if OSBPL3 expression levels may change
depending on the clinical stage of CRC, then it should be properly analyzed for use as a
biomarker.
RE: Thank you for your comment. This study mainly compares the differences in expression
levels between CRC samples and normal samples. Therefore, the difference in expression levels
of OSBPL3 you mentioned also refers to the difference between normal and disease samples,
and no differential analysis was performed on different clinical stages of CRC. In addition, we
conducted clinical independent prognostic analysis to explore the relationship between OSBPL3
and clinical features, and the results showed that the impact of OSBPL3 on the survival of CRC
patients may be affected by patient survival status, pathological T staging, and patient weight.
After that, we also explored the relationship between OSBPL3 and CRC as a biomarker, such
as immune infiltration analysis, functional enrichment analysis, drug sensitivity analysis, etc.
Therefore, OSBPL3 can be used as an independent prognostic factor in CRC to predict the
prognosis and treatment methods of patients. We will collect a large number of clinical samples
to verify our research results in the future.
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