Review for 10.1186/s12876-024-03581-5 (2025)

Title: The up-regulation of SPTAN1 expression in Pancreatic adenocarcinoma is associated
with tumor immune invasion and poor clinical prognosis
Version: 0 Date: 26 Oct 2024
Reviewer's report:
PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
No - there are minor issues
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
No - there are major issues
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are major issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
No - there are issues with the statistics in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
No - manuscript has some fundamental flaw(s)
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: In this study, Guo and collaborators investigate the role of SPTAN1,
a filamentous cytoskeletal protein, in pancreatic adenocarcinoma. They utilize publicly available
expression data across various tumor types to analyze SPTAN1 expression in comparison
to adjacent non-tumorous tissue. Additionally, they perform in vitro experiments using cell
lines derived from pancreatic adenocarcinoma (PAAD) to explore SPTAN1’s influence on cell
migration, its association with chemokines, and its role in apoptosis. Overall, the manuscript
lacks clarity in presentation. The methods are insufficiently detailed, making it challenging
to fully understand the study. Moreover, there are several statistical flaws and overstatements
throughout the manuscript.
REQUESTED REVISIONS:
Major:
Methods:
1. The description of methods is unclear, making it difficult to follow the authors’ analysis
process. For instance, it seems that the authors analyzed 33 cancer types and corresponding
normal tissues, as shown in Table 1, using an online resource. However, essential parameters
for gene expression analysis are missing. Notably, mesothelioma lacks normal tissue for
conventional expression analysis, and sarcoma has only two control samples, which challenges
the validity of these analyses.
2. The only information provided for gene expression analysis is that "the GEPIA tool was used
to analyze target genes," which is insufficient for reproducibility.
3. There is no information on the statistical methods applied in the analyses. The authors’
statement that “Bioinformatics data analysis is done automatically using online databases” is
inadequate for ensuring data reproducibility.
4. The authors mention using the GTEx database without any explanation of how or why it was
used.
Results:
Expression of SPTAN1 in Various Databases: 5. The authors report that SPTAN1 is upregulated
in five cancer types with p<0.05 but do not address the necessity of p-value correction for
multiple comparisons. Additionally, they mention SPTAN1 downregulation in four tumor types
(GBM, LUAD, LUSC, TGCT, according to Figure 1A) without further discussion.
6. The authors’ conclusion that "SPTAN1 may play a role as an oncogene" based on its elevated
expression in PAAD is an overstatement given the current data.
7. The comparison in Figure 1B, combining TCGA and GTEx data, is challenging to interpret. It
is unclear if the datasets were mixed, the number of samples analyzed, the sequencing technology
for each sample, and if any normalization was applied. This also applies to the data shown in
Figure 1C.
Correlation between Immune Infiltration and SPTAN1 Expression in PAAD: 8. There is no
description of the infiltration assay method, with only a mention of the TIMER database in this
section. Essential details, such as methodology, references, and parameters, are omitted, making
it impossible to understand or reproduce these findings.
Minor:
Pancreatic adenocarcinoma (PAAD) is only one type of pancreatic cancer. Replace "Pancreatic
Cancer" with "Pancreatic Adenocarcinoma" for clarity.
Abstract: The “Results” subsection is repeated twice.
Introduction:
First paragraph: Avoid using "etc." in listing factors influencing cancer development.
Last paragraph: “Based on our previous findings” requires a proper reference.
Methods:
Statistical analysis: Correct “online databases,The expression” by replacing the comma with a
period.