A Combined Prognostic Serum Interleukin-8 and Interleukin-6 Classifier for Stage 1 Lung Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Abstract

Hypothesis The advent of LDCT for lung cancer screening will likely lead to an increase in the detection of stage I lung cancer. Presently, these patients are primarily treated with surgery alone and ~ 30% will develop recurrence and die. Biomarkers that can identify patients for whom adjuvant chemotherapy would be a benefit could significantly reduce both patient morbidity and mortality. Herein, we sought to build a prognostic inflammatory-based classifier for stage I lung cancer. Methods We performed a retrospective analysis of 548 European American lung cancer cases prospectively enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) study. CRP, IL-6, IL-8, TNFα and IL-1β were measured using an ultrasensitive electrochemiluminescence immunoassay in serum samples collected at the time of study entry. Results IL-6 and IL-8 were each associated with significantly shorter survival (HR, 1.33; 95% CI, 1.08–1.64, P=0.007) (HR, 1.3; 95% CI, 1.09–1.67, P=0.005), respectively). Moreover, a combined classifier of IL-6 and IL-8 were significantly associated with poor outcome in stage I lung cancer patients (HR, 3.39; 95% C.I. 1.54 – 7.48, P=0.002) and in stage 1 patients with ≥30 pack-years of smoking (HR, 3.15; 95% C.I. 1.54 – 6.46, P=0.002). Conclusions These results further support the association between inflammatory markers and lung cancer outcome and suggest that a combined serum IL-6/IL-8 classifier could be a useful tool for guiding therapeutic decisions in stage I lung cancer patients.

Baseline and postoperative C-reactive protein levels predict mortality in operable lung cancer

“…Baseline CRP has been validated as prognostic marker in a variety of solid tumours [8], including LC [14], but the reason for such a prognostic effect is still unclear. Several mechanisms have been hypothesised to explain this association: (i) CRP is a marker of chronic inflammation that causes DNA injury and weakening of the immune system, enhancing carcinogenesis and tumour progression [23]; (ii) tumour cells and TIM may release several cytokines and chemokines, thus resulting in inflammatory cell infiltration into the cancer microenvironment and increasing the serum CRP concentrations [24]; (iii) tumour growth itself may cause inflammation of surrounding tissue [15] and (iv) the host may produce higher CRP levels as a result of immune response [25].…”

“…Elevated levels of circulating CRP are associated with an increased risk of LC in cancerfree individuals [9], as well as low-dose computed tomography screening participants [10], and the value of CRP in predicting disease progression and response to therapy has been widely explored in the setting of chronic inflammatory, cardiovascular and chronic obstructive pulmonary disease [11,12]. A recent metaanalysis outlined that higher baseline CRP level is associated with significantly poorer prognosis in resected LC [13], thereby suggesting that pretreatment CRP levels could be used as prognostic factors in early-stage LC, alone or in combination with other tumour or patient features [14].…”

Salivary Cytokine Levels in Lung Cancer with Distant and Regional Metastases

“…Studies on laboratory animals have demonstrated that increased levels of serum IL-6 and vascular endothelial growth factor are associated with tumor relapse; the strongest association has been found for adenocarcinoma [26]. IL-8 causes accumulation of neutrophils, which can directly kill cancer cells, but, on the other hand, IL-8 possesses angiogenic activity and thus contributes to formation of new blood vessels and therefore to the tumor development [27].…”

“…It was also reported that elevated levels of circulating IL-8 allow predicting lung cancer 5 years before manifestations of clinical symptoms [37]. In general, the combined assay of IL-6 and IL-8 in serum can be a useful tool for determination of tactics for treatment of patients with lung cancer [26]. Despite the numerous literature data, the dynamics of salivary IL-6 and IL-8 is not uniform: regardless of the histological type of lung cancer, the level of IL-6 is higher than that for the control group, while IL-8 is lower (Table 1).…”

“…A recent meta-analysis has demonstrated that a high basal level of blood CRP is associated with a worse prognosis for surgical treatment of lung cancer [42]. Thus, it can be assumed that the preoperative level of CRP can be used as a predictive factor at the early stages of lung cancer, alone or in combination with other features of the tumor or the patient [26,[43][44].…”