SCLC is a highly aggressive and chemoresponsive disease in which the best predictor of outcome appears to be staged at diagnosis . This tumor is characterized by a rapid doubling time, high growth fraction, and the early development of wide-spread metastases. Currently, no satisfactory biomarkers are available to screen for small-cell lung cancer (SCLC).
Protein expression profiling of body fluids from patients with cancer has recently become a valuable tool for obtaining information on the state of protein circuits inside tumor cells and outside the cells at the host-tumor interface. During last years, it has been demonstrated that the serum is a convenient protein-rich information reservoir that may show a systemic response to a specific disease . In serum, low molecular weight proteins and peptides that are related to this altered microenvironmental "cancerous" state can be detected.
MS instrumentation and analysis tools have continued to rapidly evolve and improve our ability to detect less-abundant serum proteins. Until now, the most commonly used instrument was the SELDI-TOF MS. This technology has been used successfully to discover potential serum diagnostic markers for breast , lung , bladder , liver , and gastric cancers. After the original highly intriguing report that the serum proteome profile can be used for the early detection of ovarian cancer, many researchers have applied the SELDI-TOF MS technology to detect proteome profiles specific for other forms of cancer and non-malignant disease. However, SELDI-TOF MS does not allow a direct identification of the discriminatory proteins and the debate about the reproducibility has been particularly strong . The new ClinProt system providing the optimal reproducibility is suitable for automated protein profiling and has the capability to simultaneously identify potential biomarker proteins. The improved sensitivity and resolution allowed detection of 400 polypeptides (0.8-15 kDa range) in a single droplet (10-50 μL) of serum, and almost 2000 unique peptides in larger sample sets, which can then be analyzed using common microarray data analysis software. It has been successfully used to identify highly sensitive and specific potential biomarkers for the diagnosis of many cancers, but similar studies of lung cancer have not been reported.
There are many tumor markers detected in the sera of patients with lung cancers. Using an array of biomarkers is one way of acquiring a differentiated cancer diagnosis. At present, this is usually performed by means of RIA or ELISA. The most extensively investigated circulating protein markers include tissue polypeptide specific antigen (TPS), neuron-specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP). It has reported that the sensitivity, specificity and accuracy of SCLC diagnosis by an indicator of TPS and NSE were 84.4%, 87.8%, 83.6% and 79.3%, 93.7%, 88.3%, respectively, In addition, the level of TPS and NSE in the patients' serum with metastatic SCLC were markedly higher than those in the patients with SCLC without metastasis, increased with the number of metastatic focuses . The presence of SOX Group B and/or ZIC2 AAs are frequently observed in small cell lung carcinoma (SCLC), and were also reported to be indicators of a better prognosis .
Here we adopted the ClinProt system to establish a fingerprint pattern including five proteins to distinguish SCLC patients from healthy individuals with a specificity of 97.73% and a sensitivity of 90.00%. 88.89% SCLC patients of the early stage were accurately diagnosed. It is noteworthy that our pattern was helpful for the diagnosis of SCLC with early stage. With the highest predictive value, the top two peaks (1778.67 and 1865.79 Da) were unqualified to selected as the set of potential biomarkers, even though they had the significant confidence. Among the five biomarkers, two were up-regulated in cancer patients, and they may be oncogene proteins. Other three were down-regulated in cancer patients, and they may be tumor suppressor gene proteins. The m/z with 5336.83 Da was lowly expressed in SCLC patients. Freed et al . also found a serum biomarker at 5337.62 Da with down-regulated in head and neck squamous cell cancer (HNSCC) samples by MALDI-TOF MS technology. Therefore, this potential biomarker remains interesting to be further investigated.