Elevated serum bilirubin levels are associated with improved survival in patients with curatively resected non-small-cell lung cancer

Li, Ning; Xu, Miao; Cai, Mu Yan; Zhou, Feng; Li, Chao Feng; Wang, Bao Xiao; Ou, Wei; Wang, Si Yu

doi:10.1016/j.canep.2015.06.007

Cited by 32 publications

(38 citation statements)

References 26 publications

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“…Li et al . demonstrated that non-small cell lung cell cancer patients with higher pretreatment bilirubin levels had longer OS, DFS, and DMFS than those with lower levels [8]. Zhang and colleagues also found that high DBIL was strongly associated with worse outcomes after surgery in colorectal cancer patients with stage II and stage III disease in a retrospective study [9]; subsequent studies confirmed these results [13, 14].…”

Section: Discussionmentioning

confidence: 95%

“…Nevertheless, recent studies have demonstrated that serum bilirubin has potent antioxidant, anti-inflammatory, and anticancer effects in colorectal cancer [5, 6]. The protective effects of serum bilirubin have been reported in lung cancer [7, 8], colorectal cancer [9], and breast cancer [10]. Additionally, decreased levels of albumin, a factor commonly used as an indicator of nutritional status, are associated with worse outcomes in gastric cancer patients [11].…”

Section: Introductionmentioning

confidence: 99%

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A nomogram based on serum bilirubin and albumin levels predicts survival in gastric cancer patients

Sun

Nie

et al. 2017

Oncotarget

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Decreases in serum bilirubin and albumin levels are associated with poorer prognoses in some types of cancer. Here, we examined the predictive value of serum bilirubin and albumin levels in 778 gastric cancer patients from a single hospital in China who were divided among prospective training and retrospective validation cohorts. X-tile software was used to identify optimal cutoff values for separating training cohort patients into higher and lower overall survival (OS) groups, based on total bilirubin (TBIL) and albumin levels. In univariate analysis, tumor grade and TNM stage were associated with OS. After adjusting for tumor grade and TNM stage, TBIL and albumin levels were still clearly associated with OS. These results were confirmed in the 299 patients in the validation cohort. A nomogram based on TBIL and albumin levels was more accurate than the TNM staging system for predicting prognosis in both cohorts. These results suggest that serum TBIL and albumin levels are independent predictors of OS in gastric cancer patients, and that an index that combines TBIL and albumin levels with the TNM staging system might have more predictive value than any of these measures alone.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

A nomogram based on serum bilirubin and albumin levels predicts survival in gastric cancer patients

Sun

Nie

et al. 2017

Oncotarget

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“…First, comparatively little attention has been paid to longitudinal and cross-sectional associations between STB levels and longevity in physically healthy individuals, and there is a paucity of such data. Second, the results of some large and seminal studies on the beneficial effects of elevated serum bilirubin levels on survival in both patients and healthy individuals are mixed (Chen et al 2008;Perlstein et al 2008;Boland et al 2014;Jørgensen et al 2014;Ong et al 2014;Li et al 2015). Further, the predictive value of STB with respect to longevity seems to decrease with age as some prospective longitudinal studies have found that in older adults slightly elevated STB levels do not confer any survival advantage (Boland et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Findings from in vivo studies show that higher than normal STB levels are strongly associated with liver-related mortality. On the other hand, a growing body of evidence suggests now that bilirubin is an important antioxidant that has several protective functions and STB levels were reported to be inversely associated with the risk of CVD (Djousse et al 2001;Vitek et al 2002;Lin et al 2006;Vitek 2012;Agrawal and Sharma 2015), arterial calcification and stiffness (Tanaka et al 2009;Zhang et al 2012;Li et al 2013), atherosclerosis (Novotny and Vitek 2003;Oda 2014;Tatami et al 2014), inflammation (Erdogan et al 2006;Vitek and Schwertner 2007;Maruhashi et al 2012;Wallner et al 2013), insulin resistance (Lin et al 2009), and cancer mortality (Temme et al 2001;Li et al 2015). Some authors suggest that increased bilirubin levels in healthy subjects are linked to low cancer mortality, especially among older men, probably because the antioxidant activity of this Unauthenticated Download Date | 5/10/18 10:49 PM pigment can help protect against ROS and cancer, which means that measurements of serum bilirubin concentrations might contribute to cancer risk estimation (Temme et al 2001).…”

Section: Discussionmentioning

confidence: 99%

“…For a long time, there has been an increasing focus on STB as a negative risk factor of cardiovascular mortality and an indicator of improved survival in both sexes, but especially in men (Djousse et al 2001;Temme et al 2001;Vitek et al 2002;Perlstein et al 2008;Kimm et al 2009;Lin et al 2009;Tanaka et al 2009;Lin et al 2010;Li et al 2013;Ong et al 2014;Kunutsor 2015;Li et al 2015). According to the oxidation-inflammation theory of aging (De la Fuente and Miquel 2009;Franceschi and Campisi 2014;, elevated serum bilirubin levels that protect against oxidative damage, atherosclerosis, CVD, tissue inflammation, etc.…”

Section: Introductionmentioning

confidence: 99%

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Association of serum bilirubin with longevity: Evidence from a retrospective longitudinal study and cross-sectional data

Chmielewski

Strzelec

Chmielowiec

et al. 2017

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Bilirubin is a potent antioxidant and an important anti-inflammatory factor. Therefore, there has been an increasing focus on serum bilirubin as a negative risk factor of cardiovascular mortality in men and an indicator of improved survival in both sexes, but the direct mechanisms of these links and the causes of sex differences are not well understood. Moreover, the evidence from longitudinal studies on effects of bilirubin on longevity is limited. In this study, we retrospectively analyzed two groups of older adults to explore age-dependent changes in serum bilirubin levels and their associations with long-term survival in both sexes. Longitudinal data from 142 individuals (68 men and 74 women) aged 45 to 70 years were compared with cross-sectional data from 225 individuals (113 men and 112 women). The latter group was divided into four categories of survival, i.e. 53, 63, 68, and 76+ based on data on lifespan. ANOVA, t-test, and regression analysis were run. The analysis of the longitudinal data showed an increase in serum total bilirubin levels in men (0.3038e 0.093x , R 2 = 0.667) and women (0.1838e, R 2 = 0.950), while the analysis of cross-sectional data revealed a U-shaped pattern of age-related changes in men (0.001x2 -0.1263x + 4.4524, R 2 = 0.999) but an inverted U-shaped pattern in women (0.0006x 2 + 0.072x -1.6924, R 2 = 0.195). On balance, these results suggest that elevated but normal bilirubin levels might confer a survival advantage in older men but not women. Alternatively, the positive relationship between serum total bilirubin and lifespan was not causal but coincidental. Further studies are needed to elucidate the direct mechanisms of the association between serum bilirubin levels and longevity in elderly people of both sexes.

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Pretreatment direct bilirubin and total cholesterol are significant predictors of overall survival in advanced non‐small‐cell lung cancer patients with EGFR mutations

Zhang

Lou

et al. 2017

Intl Journal of Cancer

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This study was designed to examine the prediction of pretreatment circulating bilirubin and cholesterol for overall survival in 459 advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. Circulating total bilirubin, direct bilirubin (DB), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured at baseline. The mean age (standard deviation) of all study patients was 58.7 (10.5) years, and 42.9% of them was males. Ever smokers accounted for 27.0% and lung adenocarcinoma for 90.4%. The median follow-up time and survival time were 29.5 and 34.9 months, respectively. Patients with higher DB had a 1.68-fold increased risk of death compared with patients with lower DB (hazard ratio [HR] = 1.68, 95% confidence interval [CI]: 1.22-2.30, p = 0.001), while patients with higher TC were at a 63% reduced risk of death compared with patients with lower TC (HR = 0.37, 95% CI: 0.20-0.67, p = 0.001). As for HDL-C, patients with higher levels had the risk of death reduced by 46% (HR = 0.54, 95% CI: 0.29-1.00, p = 0.049) compared with patients with lower levels. After the Bonferroni correction, only DB and TC were significantly associated with NSCLC survival. Our findings demonstrate for the first time that pretreatment DB was identified as a significant risk factor, yet TC as a protective factor, for overall survival in NSCLC patients with EGFR mutations.

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Elevated serum bilirubin levels are associated with improved survival in patients with curatively resected non-small-cell lung cancer

Cited by 32 publications

References 26 publications

A nomogram based on serum bilirubin and albumin levels predicts survival in gastric cancer patients

A nomogram based on serum bilirubin and albumin levels predicts survival in gastric cancer patients

Association of serum bilirubin with longevity: Evidence from a retrospective longitudinal study and cross-sectional data

Pretreatment direct bilirubin and total cholesterol are significant predictors of overall survival in advanced non‐small‐cell lung cancer patients with EGFR mutations

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