Elevated Serum Interleukin-8 Level Correlates with Cancer-Related Cachexia and Sarcopenia: An Indicator for Pancreatic Cancer Outcomes.

Ya-Chin Hou,Hui-Ling Tung,Jung-Ting Lin,Hao-Chen Wang,Ying-Jui Chao,Yan-Shen Shan,Chih-Jung Wang,Hao-Yun Chen

doi:10.3390/jcm7120502

Abstract

Cancer cachexia (CC), characterized by body weight loss and sarcopenia, contributes to over 20% of all cancer-related death. Approximately 80% of pancreatic cancer (PC) patients develop CC during disease progression. Pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, have been correlated with CC; however, its prognostic significance remains unclear. In this study, serum levels of the CC-related cytokines were determined in normal donors and PC patients. IL-8 expression was assessed in PC tissue microarrays. The correlation of levels of each cytokine with disease progression, weight loss, and sarcopenia was calculated. The relationships among the baseline variables, CC, and IL-8 expression with disease progression were examined using univariate and multivariate analyses. Of these mentioned cytokines, only serum IL-8 level was elevated in the locally advanced group (n = 55) compared with the normal (n = 17) and resected groups (n = 55). Serum IL-8 level was positively correlated with CC status, weight loss, sarcopenia, but was negatively correlated with total psoas area (TPA). IL-8 expression in tissue samples was also positively associated with weight loss. Furthermore, serum IL-8 level was an independent predictor of survival. In conclusion, elevated serum IL-8 level significantly correlates with CC and sarcopenia and can be used as a prognostic indicator in PC.

Highlights

Cancer cachexia (CC), a syndrome defined by unintended weight loss greater than 5% in over 6 months or sarcopenia with any degree of weight loss greater than 2%, is a major cause of death in more than 20% of all cancer patients [1,2]
Given that pancreatic cancer (PC) patients have the highest frequency of weight loss than those with other common cancers [13], our primary objective in this study was to explore the association of CC status with the serum IL-1β, IL-6, interleukin-8. CC and IL-8 expression (IL-8), or tumor necrosis factor (TNF)-α levels in patients with resected or locally advanced PC
Higher serum levels of IL-1β, IL-6, IL-8, and TNF-α were observed in cancer patients of the locally advanced group than those of the normal and resected groups

Summary

Introduction

Cancer cachexia (CC), a syndrome defined by unintended weight loss greater than 5% in over 6 months or sarcopenia with any degree of weight loss greater than 2%, is a major cause of death in more than 20% of all cancer patients [1,2]. Tumor removal is probably the best way to cure CC [6]; more than 80% of PC patients have unresectable disease and should be treated with systemic chemotherapy, the main method for prolonging survival its effectiveness is limited [4,7]. Several pro-inflammatory cytokines, including IL-1β, IL-6, IL-8, and TNF-α, have been implicated in the clinical features of CC in patients with gastrointestinal or non-small cell lung cancer [11,12], whether detecting these cytokines is effective in predicting the prognosis of patients with CC remains uncertain. Given that PC patients have the highest frequency of weight loss than those with other common cancers [13], our primary objective in this study was to explore the association of CC status with the serum IL-1β, IL-6, IL-8, or TNF-α levels in patients with resected or locally advanced PC. The secondary objective was to evaluate the prognostic utility of IL-8 protein expression alone and in combination with CC status in PC

Study Population and Clinical Parameters

59 CC p-Value4 Non-CC51 CC p-Value

Findings

Discussion