Early stage
lung cancer detection is the first step toward successful clinical
therapy and increased patient survival. Clinicians monitor
cancer progression by profiling
tumor cell
proteins in the blood plasma of afflicted patients. Blood plasma, however, is a difficult
cancer protein assessment medium because it is rich in
albumins and heterogeneous
protein species. We report herein a method to detect the
proteins released into the circulatory system by
tumor cells. Initially we analyzed the
protein components in the
conditioned medium (CM) of
lung cancer primary cell or organ cultures and in the adjacent normal bronchus using one-dimensional PAGE and nano-ESI-MS/MS. We identified 299
proteins involved in key cellular process such as cell growth, organogenesis, and signal transduction. We selected 13 interesting
proteins from this list and analyzed them in 628 blood plasma samples using ELISA. We detected 11 of these 13
proteins in the plasma of
lung cancer patients and non-patient controls. Our results showed that plasma
matrix metalloproteinase 1 levels were elevated significantly in late stage
lung cancer patients and that the plasma levels of 14-3-3 sigma, beta, and eta in the
lung cancer patients were significantly lower than those in the control subjects. To our knowledge, this is the first time that
fascin,
ezrin, CD98,
annexin A4, 14-3-3 sigma, 14-3-3 beta, and 14-3-3 eta
proteins have been detected in human plasma by ELISA. The preliminary results showed that a combination of CD98,
fascin,
polymeric immunoglobulin receptor/
secretory component and 14-3-3 eta had a higher sensitivity and specificity than any single marker. In conclusion, we report a method to detect
proteins released into blood by
lung cancer. This pilot approach may lead to the identification of novel
protein markers in blood and provide a new method of identifying
tumor biomarker profiles for guiding both early detection and
therapy of human
cancer.