Circulating interleukin‐6 level is a prognostic marker for survival in advanced nonsmall cell lung cancer patients treated with chemotherapy

Abstract

Lung cancer is the leading cause of cancer death worldwide as well as in Taiwan. Interleukin-6 (IL-6) is a multifunctional cytokine and has been implicated in tumor progression. This study recruited 245 patients with advanced (Stage 3B/4) nonsmall cell lung cancer (NSCLC) that had received chemotherapy, to evaluate associations between IL-6 and lung cancerspecific survival. Among these subjects, 112 gave blood samples before and 133 after the start of chemotherapy. Plasma IL-6 was measured using an enzyme linked-immunosorbent assay. The 33rd and 66th percentiles of IL-6 concentrations were 2.01 and 25.16 for the 245 patients and were defined as the cutoff points for dividing the patients into low, intermediate and high groups. Kaplan-Meier and Cox proportional-hazard models were used to evaluate the relationship between the IL-6 level and survival time. Results after adjusting for age, sex, smoking history, histologic type and stage of lung cancer revealed a significant relationship. For all patients, the hazard ratio with high IL-6 levels for lung cancer-specific survival was 2.10 [95% confidence interval (CI) 5 1.49 2 2.96] compared with low IL-6 levels. The hazard ratio for patients who were recruited before and after the start of chemotherapy was1.25 (95% CI 5 0.73 2 2.13) and 3.66 (95% CI 5 2.18 2 6.15), respectively. Patients with high circulating IL-6 also responded poorly to chemotherapy. Therefore, a high level of circulating IL-6 was associated with an inferior response and survival outcome in NSCLC patients treated with chemotherapy.

Interleukin levels and their potential association with venous thromboembolism and survival in cancer patients

“…IL-6 is known to directly promote tumour growth, but also facilitates immune invasion by several signalling pathways, in particular the signal transducer and transcription activator 3 [36]. Moreover, IL-6 might not only be induced by chemotherapy, but also mediate therapy resistance, which could add to the worse prognosis of patients with high circulating IL-6 levels [38]. Interestingly, in a former study by our group, enhanced levels of C-reactive protein (CRP), an acute-phase protein known to be induced strongly by IL-6, indicated a worse prognosis of cancer patients not associated with VTE frequency [13].…”

“…Previous studies have already shown that elevated levels of IL-6 correlated with lower survival rates [30,43] of cancer patients, including those of metastatic breast cancer [44], gastrointestinal cancer [28], metastatic renal cell carcinoma [29] prostate cancer [45] and lung cancer [46,47].…”

“…IL-10, which acts as an immunoinhibitory cytokine, is often elevated in patients with lung cancer, whereas in patients with colorectal cancer bs_bs_banner Clinical and Experimental Immunology ORIGINAL ARTICLE doi:10.1111/cei.12308 the levels of IL-6 are increased [19,21,[23][24][25]. Elevated levels of circulating IL-6 and IL-8 are often associated with poor survival rates, especially in patients suffering from lung cancer [24,[26][27][28][29][30]. The macrophage inflammatory protein-1α [CCL-3 (chemokine ligand 3)] is involved in acute inflammation via recruiting and activating leucocytes [31].…”

Expression of interleukin-6 is associated with epithelial-mesenchymal transition and survival rates in gallbladder cancer

“…If cancer cells increasingly secrete IL-6, it may act in an autocrine manner to enhance the metastatic ability (17) and resistance of the tumor to treatment (18). The increased levels of IL-6 have been correlated with poor prognosis and survival rate in a variety of types of cancer (19)(20)(21)(22). Previous studies on solid tumors, including gastric, renal cell, colorectal, prostate, non-small cell lung, melanoma and head and neck cancer and hematologic malignancies, including myeloma and non-Hodgkin's lymphoma, have indicated the potential prognostic significance of IL-6 levels (19)(20)(21)(22).…”

Koncentracije th1 i th2 citokina u mikrocirkulaciji tumora i u serumu kod bolesnika sa SCLC i NSLC

“…Vrlo retko su u istraživanjima uključene obe grupe bolesnika s karcinomom pluća. Chang i suradnici su istraživali vrednosti IL6 u uzorcima seruma iz SCLC i sva tri oblika NSCLC (19). Oni su pokazali da povećanje IL6 je povezano s brzim napretkom bolesti i lošim odgovorom na terapiju kod svih bolesnika sa LC.…”