LKB1 Loss Assessed by Immunohistochemistry as a Prognostic Marker to First-Line Therapy in Advanced Non-Small-Cell Lung Cancer

Round 1

Reviewer 1 Report

This manuscript described the relationship between Liver Kinase B1 (LKB1) and the prognosis of non-small cell lung cancer (NSCLC). The authors are trying to demonstrate that patients with an LKB1 loss had worse clinical outcomes and warrant prospective assessments to confirm the prognostic role of the LKB1 expression in advanced NSCLC. Overall, this is an interesting study demonstrating some interesting results. However, there are several issues with the manuscript in its current form which require attention before it can be recommended for publication.

- There is no ethics description in the manuscript's main text. Could the authors confirm that all this study has been approved by the ethics committee in the main text when involved in human data/samples?

- The authors should mention the full name of an abbreviation in the first time used in the main text. e.g.

ECOG PS - Eastern Cooperative Oncology Group Performance Score 

EGFR - Epidermal growth factor receptor

- As the authors mentioned in the Table 1, statistically significant p-values are in bold. However, the p value of smoking status was not bold as it was 0.005.

 

 

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 2 Report

The manuscript from Avilés-Salas and colleagues titled “LKB1 loss assessed by immunohistochemistry as a prognostic marker to first-line therapy in advanced non-small cell lung cancer” evaluates LKB1 expression by immunochemistry as a prognostic biomarker in advanced NSCL cancer. Using this technique in a retrospective cohort of 110 patients, the authors show that the low expression of LKB1 is associated with worse clinical outcomes, evaluated on PFS and OS.

The goal of this study, according to the authors, is to establish IHC as an accessible technique to assess LKB1 expression at a low cost for countries that do not have wide access to NGS, which is the case in LATAM.

Overall, the manuscript and its conclusion are clears. However, reading the tables and figures is sometimes difficult.

 

Several points need to be considered to improve the manuscript.

 

Major points:

- This study concerns the evaluation of LKB1 expression by immunochemistry, but there no figure of IHC to show positive and negative staining as examples. A figure must be added.

- Concerning the immunodetection of LKB1, does the antibody clone used in the study has already been validated in other studies? Did the authors used a non-immune control immunoglobulin condition to ensure the specificity of the staining?  

- The authors clearly explain that they could not compare IHC results to genetic analysis as the latter was not performed in their study due to low accessibility. Did other studies make this comparison? If it the case, what is the result of this comparison? This must be added  and discuss in the discussion part.

- What could be the impact on clinical management of the detection of low LKB1 expression, considered as a poor prognostic maker in advanced NSCL carcinoma? This must be discussed to justify the usefulness of this detection for the clinician and therapeutic care.

 

Minor points:

- In Materials and Methods, 2 paragraph titles must be added for lines 77 to 104: 2.1 Patients (lines 77-91) and 2.2 IHC stain (lines 92-104).

- The authors must add a 3.1 paragraph with title for first part of results (lines 131-145).

- Tables and figures must be improved to be more readable.

- Gene names must be indicated in italics (e.g. line 54).

- Change IHQ to IHC in the text. 

Author Response

Please see the attachment.

Author Response File: Author Response.docx