Perilipin1 Expression as a Prognostic Factor in Patients with Squamous Cell Carcinoma of the Lung

Round 1

Reviewer 1 Report

The submitted article focus on the value of the perilipin 1 expression as a prognostic factor in patients with squamous cell carcinoma of the lung. The relationship between lipid metabolism and cancer development may have a potential interest.

 Concerning lung cancer, the  authors focus on squamous cell carcinoma. Do the authors know if there are similar results in other types of lung cáncer? Could the authors derive from their study any dietetic or metabolic recommendatios for patients with lung cáncer o widely, about some lyfestyle for general population?

Author Response

Thank you very much for your interest in our paper. According to the literature review we conducted, we could not find any reported cases of other types of lung cancer, i.e. adenocarcinoma, neuroendocrine carcinoma. The motivation of our study was also to help with dietary or metabolic recommendations for patients with lung squamous cell carcinoma. For the suggestion of the reviewer, we believe that prospective cohort studies should be conducted in the future to provide specific dietary or metabolic recommendations. Based on this study, our group plans to study the correlation between perilipin 1 expression and patient prognosis in lung adenocarcinoma, neuroendocrine carcinoma, and to study the correlation between meat intake and patient prognosis in lung squamous cell carcinoma in a prospective study. Again, thank you for your sincere advice

Reviewer 2 Report

Dr. Min Hye Kim and colleagues studied PLIN1 and investigated the correlation between PLIN1 expression and the prognosis of lung squamous cell carcinoma. However, several points in this paper need to be corrected.

My comments are listed below.

Major comments:

1.        If the authors mention that PLIN1 is a "prognostic factor" in squamous cell carcinoma, I believe that overall survival (OS) data is essential. Please add the results and discussions related to OS. Additionally, considering the importance of information regarding post-recurrence treatment, it is advisable to include such details. The current description does not conclusively " PLIN1" as a prognostic factor but instead suggests it as a risk for recurrence.

2.        Since the authors are conducting DFS analysis using surgical samples, details about the surgery (such as surgical procedures and information on R0 surgery) and the presence or absence of postoperative adjuvant therapy should be explained in the paper. Were there differences in these background details between the two groups?

Minor comments:

1.        It is mentioned in the "Methods" section that the TNM classification based on AJCC was used, but please specify which edition of the TNM classification was cited.

2.        For the Kaplan-Meier curves, please add annotations for "Number at risk" and indicators for censored data.

Author Response

Major comments:

1.If the authors mention that PLIN1 is a "prognostic factor" in squamous cell carcinoma, I believe that overall survival (OS) data is essential. Please add the results and discussions related to OS. Additionally, considering the importance of information regarding post-recurrence treatment, it is advisable to include such details. The current description does not conclusively " PLIN1" as a prognostic factor but instead suggests it as a risk for recurrence.

<Answer>

Yes, I understand what you are saying very well. Thank you for your logical advice. As you said, overall survival is an important factor in disease prognosis studies. However, this study was designed to look at disease free survival and disease specific survival as important prognostic factors. Lung cancer is known to have a very low 5-year survival rate, and in this study, the 45 patients with confirmed deaths had a mean survival of only 19.29 months. To determine overall survival, we further reviewed recent hospital records for 49 of the 94 patients with no confirmed deaths (Censored), but no additional records were identified. In addition, postoperative recurrence was identified in 52 patients, and recurrence was either in the form of local recurrence or distant metastases. The patients enrolled in this study were all treated according to the National Comprehensive Cancer Network (NCCN) guidelines at a single institution, which suggests a degree of consistency in treatment. In this study, we conducted a retrospective statistical analysis of the events of recurrence and death that occurred during treatment according to NCCN guidelines at a single institution. The overall survival that the reviewer is referring to is similar to disease-specific survival in this study, given that lung cancer is a deadly disease with a short survival time. The study also included statistical analysis of pathology findings. Perilipin 1 expression was significantly (p=0.03) higher in patients with shorter disease-free survival, with a hazard ratio of 2.178. To reduce the bias that may be seen in retrospective statistical articles, we performed a Cox regression analysis with confounding variables, and the results were statistically significant. In this study, we considered statistical significance only when the p value was less than 0.05.

 The statistical results of the association between perilipin 1 and the prognosis of patients with pulmonary squamous cell carcinoma presented in this study will be re-validated in the future by our team in the departments of thoracic surgery, respiratory medicine, and medical oncology, and by other research methods, including prospective studies. We strongly agree with the reviewer's comments, and in future prospective studies, we will conduct studies designed for overall survival and progression-free survival. Thank you. Please Please see the attached Word file.

2. Since the authors are conducting DFS analysis using surgical samples, details about the surgery (such as surgical procedures and information on R0 surgery) and the presence or absence of postoperative adjuvant therapy should be explained in the paper. Were there differences in these background details between the two groups?

<Answer>

Thank you. We strongly agree with the reviewer. The main treatment for lung squamous cell carcinoma is surgery. We have added surgical procedure information to Table 1 clinicopathological data.

The correlation between perilipin 1 expression and surgical procedures has been added to Table 2.

We have also added a breakdown of patient survival by surgical procedure to Table 3.

Only cases with R0 surgery were enrolled in this study, and we have added this information to the Materials and Methods section.

In addition, the patients included in this case, both the perilipin 1 high expression group and the perilipin 1 low expression group, received postoperative adjuvant therapy according to NCCN guidelines from 2002. As reviewers know, there are many factors that determine postoperative adjuvant therapy, including patient health status and socioeconomic status. Although the presence of chemotherapy and the number and dose of treatments are also important factors affecting patient outcomes, we believe that our study population was somewhat consistent in that it was a group of patients who received clinically best treatment based on NCCN guidelines at a single institution. In addition, several patients were transferred to other hospitals in case of recurrence, so they were not aware of the correct post-operative treatment. We have separately investigated the clinical information of 11 patients with high expression of perilipin 1, and the results are as follows. We have added this information as Table 4 in the manuscript. In the case of patient no.2, she was transferred to another hospital after the recurrence, but there was a limitation of not knowing the exact post-recurrence therapy. Thank you again for your important advice.

Minor comments:

1. It is mentioned in the "Methods" section that the TNM classification based on AJCC was used, but please specify which edition of the TNM classification was cited.

<Answer>

In this study, the patients' staging was revised to AJCC 8th edition, which is mentioned in the "Methods" section.

2. For the Kaplan-Meier curves, please add annotations for "Number at risk" and indicators for censored data.

<Answer>

I added the Number at risk and censored data to the Kaplan-Meier curves. thank you.

Round 2

Reviewer 2 Report

The authors promptly and accurately addressed my review. Additionally, I overlooked the consideration of approximating the OS to DSS in the paper. I apologize for this oversight. 'Perilipin1' can be a prognostic factor in squamous cell carcinoma, and the authors' study is deemed to contribute to future research on lung cancer. I have determined that the revisions to the authors' paper are acceptable.