Serum Cytokines Correlate with Pretreatment Body Mass Index-adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery

Abstract

Serum Cytokines Correlate with Pretreatment Body Mass Index-Adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery. Circulating cytokines have been linked to the development of esophageal squamous cell carcinoma (ESCC) and its associated malnutrition process. Nonetheless, given the varied disease stages and treatment modalities in previous studies, the clinical relevance of their findings is limited. We retrospectively studied 52 patients with stage III ESCC who underwent neoadjuvant chemoradiotherapy and curative-intent surgery. We investigated the association of clinicopathological features, pretreatment laboratory data, and pretreatment inflammatory status, as indicated by the levels of albumin, C-reactive protein, and 10 circulating cytokines, namely tumor necrosis factor-alpha (TNF-α), interferon-gamma, interleukin-1-beta (IL-1β), IL-4, IL-6, IL-8, IL-12, IL-13, IL-17A, and IL-23, with malnutrition, as shown by body mass index-adjusted body weight loss (BMI-BWL) grading, cancer progression. Half the patients showed severe malnutrition and high BMI-BWL grades (3 and 4). Multivariate analysis revealed an independent association between the levels of three cytokines (TNF-α, ≤ 5.8 pg/ml; IL-1β, > 0.4 pg/ml; IL-6, ≤ 12.4 pg/ml) and high BMI-BWL grades and between IL-4 levels > 22.5 pg/ml and cancer progression. All 10 cytokines were closely correlated with each other. In conclusion, TNF-α, IL-1β, and IL-6 were independent markers of malnutrition status and IL-4 was a prognostic factor for cancer progression in this patient population.

Acknowledgments

The authors would like to thank the Chang Gung Medical Foundation, Keelung Chang Gung Memorial Hospital Tissue Bank, and Biobank for providing the study materials. The authors are also grateful to Li-Ting Lien for technical contributions, and the staff members of the Department of Hematology/Oncology of Chang Gung Memorial Hospital for their valuable assistance.

Author contributions

KYY designed the study protocol, conducted the study, interpreted the results, and revised the entire manuscript. YPP organized the original data and drafted the entire manuscript. HCK conducted the statistical analysis and prepared Tables 1A and 1B. JYL collected the demographic data, analyzed the survival data, and prepared Tables 2A–2E and Fig. 1. WCC provided scholarly interpretation in the result and discussion sections. PHC prepared Tables 3A and 3B. HHL created Fig. 2 and revised the final versions of the introduction and discussion.

All authors critically revised, read, and approved the final manuscript and agreed to be fully accountable for ensuring the integrity and accuracy of this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are not publicly available because of privacy of research participants but can be acquired from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by grants (CGRPG2F0061 and CMRPG2J0041) from the Chung Gang Memorial Hospital, Keelung, Taiwan.