Sex-determining region of Y chromosome-related high-mobility-group box 2 in malignant tumors: current opinions and anticancer therapy / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To gain insight into the mechanism by which sex-determining region of Y chromosome (SRY)-related high-mobility-group box 2 (SOX2) involved in carcinogenesis and cancer stem cells (CSCs).</p><p><b>DATA SOURCES</b>The data used in this review were mainly published in English from 2000 to present obtained from PubMed. The search terms were "SOX2," "cancer," "tumor" or "CSCs."</p><p><b>STUDY SELECTION</b>Articles studying the mitochondria-related pathologic mechanism and treatment of glaucoma were selected and reviewed.</p><p><b>RESULTS</b>SOX2, a transcription factor that is the key in maintaining pluripotent properties of stem cells, is a member of SRY-related high-mobility group domain proteins. SOX2 participates in many biological processes, such as modulation of cell proliferation, regulation of cell death signaling, cell apoptosis, and most importantly, tumor formation and development. Although SOX2 has been implicated in the biology of various tumors and CSCs, the findings are highly controversial, and information regarding the underlying mechanism remains limited. Moreover, the mechanism by which SOX2 involved in carcinogenesis and tumor progression is rather unclear yet.</p><p><b>CONCLUSIONS</b>Here, we review the important biological functions of SOX2 in different tumors and CSCs, and the function of SOX2 signaling in the pathobiology of neoplasia, such as Wnt/β-catenin signaling pathway, Hippo signaling pathway, Survivin signaling pathway, PI3K/Akt signaling pathway, and so on. Targeting towards SOX2 may be an effective therapeutic strategy for cancer therapy.</p>

Detection of lung adenocarcinoma using magnetic beads based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry serum protein profiling / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recently, due to the rapid development of proteomic techniques, great advance has been made in many scientific fields. We aimed to use magnetic beads (liquid chip) based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) technology to screen distinctive biomarkers for lung adenocarcinoma (adCA), and to establish the diagnostic protein profiles.</p><p><b>METHODS</b>Using weak cation exchange magnetic beads (MB-WCX) to isolate and purify low molecular weight proteins from sera of 35 lung adCA, 46 benign lung diseases (BLDs) and 44 healthy individuals. The resulting spectra gained by anchor chip-MALDI-TOF-MS were analyzed by ClinProTools and a pattern recognition genetic algorithm (GA).</p><p><b>RESULTS</b>In the working mass range of 800 - 10 000 Da, 99 distinctive peaks were resolved in lung adCA versus BLDs, while 101 peaks were resolved in lung adCA versus healthy persons. The profile gained by GA that could distinguish adCA from BLDs was comprised of 4053.88, 4209.57 and 3883.33 Da with sensitivity of 80%, specificity of 93%, while that could separate adCA from healthy control was comprised of 2951.83 Da and 4209.73 Da with sensitivity of 94%, specificity of 95%. The sensitivity provided by carcinoembryonic antigen (CEA) in this experiment was significantly lower than our discriminatory profiles (P < 0.005). We further identified a eukaryotic peptide chain release factor GTP-binding subunit (eRF3b) (4209 Da) and a complement C3f (1865 Da) that may serve as candidate biomarkers for lung adCA.</p><p><b>CONCLUSION</b>Magnetic beads based MALDI-TOF-MS technology can rapidly and effectively screen distinctive proteins/polypeptides from sera of lung adCA patients and controls, which has potential value for establishing a new diagnostic method for lung adCA.</p>

Study of differential proteins in lung adenocarcinoma using laser capture microdissection combined with liquid chip-mass spectrometry technology / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In recent years the proportion of lung adenocarcinoma (adCA) which occurs in lung cancer patients has increased. Using laser capture microdissection (LCM) combined with liquid chip-mass spectrometry technology, we aimed to screen lung cancer biomarkers by studying the proteins in the tissues of adCA.</p><p><b>METHODS</b>We used LCM and magnetic bead based weak cation exchange (MB-WCX) to separate and purify the homogeneous adCA cells and normal cells from six cases of fresh adCA and matched normal lung tissues. The proteins were analyzed and identified by matrix assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-OF-MS). We screened for the best pattern using a radial basic function neural network algorithm.</p><p><b>RESULTS</b>About 2.895 × 10(6) and 1.584 × 10(6) cells were satisfactorily obtained by LCM from six cases of fresh lung adCA and matched normal lung tissues, respectively. The homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. Comparing the differentially expressed proteins between the lung adCA and the matched normal lung group, 221 and 239 protein peaks, respectively, were found in the mass-to-charge ration (M/Z) between 800 Da and 10 000 Da. According to t test, the expression of two protein peaks at 7521.5 M/Z and 5079.3 M/Z had the largest difference between tissues. They were more weakly expressed in the lung adCA compared to the matched normal group. The two protein peaks could accurately separate the lung adCA from the matched normal lung group by the sample distribution chart. A discriminatory pattern which can separate the lung adCA from the matched normal lung tissue consisting of three proteins at 3358.1 M/Z, 5079.3 M/Z and 7521.5 M/Z was established by a radial basic function neural network algorithm with a sensitivity of 100% and a specificity of 100%.</p><p><b>CONCLUSIONS</b>Differential proteins in lung adCA were screened using LCM combined with liquid chip-mass spectrometry technology, and a biomarker model was established. It is possible that this technology is going to become a powerful tool in screening and early diagnosis of lung adCA.</p>

Serum amyloid A protein: a potential biomarker correlated with clinical stage of lung cancer / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To identify serum diagnosis or progression biomarkers in patients with lung cancer using protein chip profiling analysis.</p><p><b>METHOD</b>Profiling analysis was performed on 450 sera collected from 213 patients with lung cancer, 19 with pneumonia, 16 with pulmonary tuberculosis, 65 with laryngeal carcinoma, 55 with laryngopharyngeal carcinoma patients, and 82 normal individuals. A new strategy was developed to identify the biomarkers on chip by trypsin pre-digestion.</p><p><b>RESULTS</b>Profiling analysis demonstrated that an 11.6 kDa protein was significantly elevated in lung cancer patients, compared with the control groups (P < 0.001). The level and percentage of 11.6 kDa protein progressively increased with the clinical stages I-IV and were also higher in patients with squamous cell carcinoma than in other subtypes. This biomarker could be decreased after operation or chemotherapy. On the other hand, 11.6 kDa protein was also increased in 50% benign diseases of lung and 13% of other cancer controls. After trypsin pre-digestion, a set of new peptide biomarkers was noticed to appear only in the samples containing a 11.6 kDa peak. Further identification showed that 2177 Da was a fragment of serum amyloid A (SAA, MW 11.6 kDa). Two of the new peaks, 1550 Da and 1611 Da, were defined from the same protein by database searching. This result was further confirmed by partial purification of 11.6 kDa protein and MS analysis.</p><p><b>CONCLUSION</b>SAA is a useful biomarker to monitor the progression of lung cancer and can directly identify some biomarkers on chip.</p>