Circulating levels of immune and inflammatory markers and long versus short survival in early-stage lung cancer
ANNALS OF ONCOLOGY
Authors: Bodelon, C.; Polley, M. Y.; Kemp, T. J.; Pesatori, A. C.; McShane, L. M.; Caporaso, N. E.; Hildesheim, A.; Pinto, L. A.; Landi, M. T.
Abstract
Some patients diagnosed with early-stage lung cancer and treated according to standard care survive for only a short period of time, while others survive for years for reasons that are not well understood. Associations between markers of inflammation and survival from lung cancer have been observed. Here, we investigate whether circulating levels of 77 inflammatory markers are associated with long versus short survival in stage I and II lung cancer. Patients who had survived either < 79 weeks (similar to 1.5 years) (short survivors, SS) or > 156 weeks (3 years) (long survivors, LS) were selected from a retrospective population-based study. Logistic regression was used to calculate adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The false discovery rate was calculated to adjust for multiple testing. A total of 157 LS and 84 SS were included in this analysis. Thirteen markers had adjusted OR on the order of 2- to 5-fold when comparing the upper and lower quartiles with regard to the odds of short survival versus long. Chemokine CCL15 [chemokine (C-C motif) ligand 15] was the most significant marker associated with increased odds of short survival (ORs = 4.93; 95% CI 1.90-12.8; q-value: 0.042). Smoking and chronic obstructive pulmonary disease were not associated with marker levels. Our results provide some evidence that deregulation of inflammatory responses may play a role in the survival of early-stage lung cancer. These findings will require confirmation in future studies.
Hemofiltrate CC chemokines with unique biochemical properties: HCC-1/CCL14a and HCC-2/CCL15
JOURNAL OF LEUKOCYTE BIOLOGY
Authors: Forssmann, U; Magert, HJ; Adermann, K; Escher, SE; Forssmann, WG
Abstract
The hemofiltrate CC chemokines CCL14a (formerly HCC-I), CCL14b (formerly HCC-3), and CCL15 (formerly HCC-2) are encoded by mono- as well as bicistronic transcripts from a tandem gene arrangement on human chromosome 17q11.2. The transcription and splicing into several mono- and bicistronic transcripts of this gene complex are unique for human genes. No corresponding mechanism is known in nonprimate mammalian species such as mice and rats. The extremely high concentration of CCL14a in human Plasma is exceptional for chemokines and led to the identification of this chemokine. Several molecular forms of CCL14a have been isolated and investigated. The mature propeptide CCL14a(1-74) is a low-affinity agonist of CCR1 which is converted to a high-affinity agonist of CCR1 and CCR5 on proteolytic processing by serine proteases. In contrast, CCL15 is characterized using molecular forms deduced from the mRNA/cDNA and shown to activate cells via CCR1 and CCR3, also dependent on the amino-terminal length. Hemofiltrate CC chemokines are chemoattractants for different types of leukocytes including monocytes, eosinophils, T cells, dendritic cells, and neutrophils. In this review, we emphasize the genomic organization, expression patterns, and biochemical properties of CCL14a, CCL14b, and CCL15. We report results of significance for the development of therapeutic strategies, especially concerning HIV infection and inflammatory diseases.