Serum midkine as non-invasive biomarker for detection and prognosis of non-small cell lung cancer.

Lung cancer continues to be the leading cause for cancer-related deaths in men and women worldwide. Sufficient screening tools enabling early diagnosis are essential to improve patient outcomes. The aim of this study was to evaluate serum midkine (S-MK) both as a diagnostic and prognostic biomarker in non-small cell lung cancer (NSCLC). This single-center analysis included 59 NSCLC patients counting 30 squamous cell cancers and 29 adenocarcinomas. Preoperative S-MK concentration was determined using ELISA. Patients were followed up to five years. S-MK was found to be significantly overexpressed in patients with NSCLC compared to healthy controls (p < 0.001). The discriminative power of S-MK to differentiate NSCLC subjects from controls was fairly high with an area under the receiver operating characteristic curve of 0.83 (p < 0.001). Optimal sensitivity of 92% and reasonable specificity of 68% was reached at a threshold of 416 pg/ml S-MK. Patients with high S-MK concentration showed a significantly shorter overall survival compared to patients with low S-MK expression (p < 0.05). In conclusion, S-MK is overexpressed in patients with NSCLC and serves as an independent prognostic factor for overall survival. S-MK may thus be considered as an additional non-invasive biomarker not only for NSCLC screening but also for outcome prediction.

Prognostic value of posttreatment HPV-specific antibodies in patients with oropharyngeal tumors.

BACKGROUND: The presence of human papillomavirus (HPV)-specific antibodies in patients with head and neck cancer at enrollment has prognostic significance. In cervical carcinoma patients, the decrease of HPV E6/E7-specific antibodies appears to be associated with a better prognosis. METHODS: This prospective study with follow-up focused on the persistence and prognostic value of antibodies specific for HR HPV-derived VLPs and HPV16 E6/E7 oncoproteins in patients with oropharyngeal cancers. In this study, we analyzed sera of 93 patients taken a year after the end of treatment and sera from 58 of these patients taken up to 14 years after treatment. RESULTS: The level of HPV-specific antibodies decreased on the 1-year follow-up and the decrease during the long follow-up was statistically significant. For HPV16 E7 antibodies the decrease was steeper in nonrecurrent patients. While the level of antibodies at enrollment was not predictive of recurrences, the decrease of HPV16 E6 antibodies at 1-year follow up was associated with better overall as well as disease-specific survival of patients. CONCLUSIONS: The data suggest that the pretreatment level of HPV-specific antibodies is not predictive of the occurrence of recurrences but the decrease HPV16 E6 antibodies on the 1-year follow-up is predictive of better survival of HN patients.

Less circulating mucosal-associated invariant T cells in patients with cervical cancer.

OBJECTIVE: Mucosal-associated invariant T cells (MAITs) are important for immune defense against infectious pathogens and regulation of various inflammatory diseases. However, their roles in cancer are rarely reported. Since cervical cancer is one of the diseases involving mucosal tissue, we try to investigate the association between circulating MAITs and cervical cancer. MATERIALS AND METHODS: Blood samples were obtained from patients with cervical cancer (n = 47) and healthy individuals (n = 39). We determined phenotypic MAITs in peripheral blood mononuclear cells (PBMCs) and evaluated the percentage of MAITs in CD3+ cells by flow cytometry. The percentage of MAITs was stratified according to Federation of Gynecology and Obstetrics (FIGO) staging system in patients with cervical cancer. Progression-free survival (PFS) with respect to the amount of MAITs was also analyzed. RESULTS: The percentage of circulating MAITs in patients with cervical cancer was significantly lower than in healthy group (0.987% vs. 4.008%, p < 0.0001). In subgroup analysis, though not statistically significant, it showed a trend of lower percentage of circulating MAITs in cervical cancer patients with FIGO stage II-IV disease than in patients with FIGO stage I disease (0.4045% vs. 1.098%, p = 0.11). A trend of poor PFS in patients with lower circulating MAITs was also noted. CONCLUSION: MAITs play a crucial role in cancer immunity. The decrease of MAITs in peripheral blood is related to cervical cancer. There is a trend of lower percentage of MAITs in advanced stages and lower percentage of MAITs towards poor PFS in patients with cervical cancer.

Circulating Heat Shock Protein 70 Is a Novel Biomarker for Early Diagnosis of Lung Cancer.

Heat shock protein 70 (HSP70) was a highly conserved protein which was significantly induced in response to cellular stresses. HSP70 played an important role in the pathogenesis of cancer which stabilized the production of large amount of oncogenic proteins and finally supported growth and survival of tumor. However, there was no report about the diagnosis of circulating HSP70 in lung cancer patients. In this study, a total of 297 participants (lung cancer: 197, healthy control: 100) were enrolled in the detection of circulating HSP70 level in plasma by ELISA assay. The results indicated that circulating HSP70 significantly decreased in lung cancer patients compared to healthy controls (P < 0.0001). Receiver operating characteristic (ROC) analysis showed that HSP70 (AUC: 82.2%, SN: 74.1%, SP: 80.0%) had higher diagnosis value than clinical existing biomarkers CEA (AUC: 80.1%, SN: 76.8%, SP: 67.3%) and CA 19-9 (AUC: 63.7%, SN: 64.2%, SP: 54.0%). In the analysis of early lung cancer patients, ROC results also revealed that HSP70 (AUC: 83.8%, SN: 71.2%, SP: 84.0%) have higher sensitivity, specificity, and AUC than CEA (AUC: 73.7%, SN: 73.2%, SP: 69.1%) and CA 19-9 (AUC: 61.5%, SN: 69.4%, SP: 53.4%). In analysis of specific histological classifications, HSP70 showed more valuable in the diagnosis of SCC (AUC: 85.9%, SN: 86.1.9%, SP: 81.0%) than ADC (AUC: 81.0%, SN: 69.1%, SP: 81.0%). Combined analysis of HSP70 and existing biomarker: CEA and CA 19-9 exhibited that HSP70 combined CEA and CA 19-9 showed the highest AUC (0.945, 95% CI, 0.855-1.000). The importance of our results was that we found decreased circulating HSP70, in combination with elevated CEA and CA 19-9, could be utilized in the diagnosis of early (stage I and II) lung cancer.

Plasma selenoprotein P concentration and lung cancer risk: results from a case-control study nested within the Shanghai Men's Health Study.

Selenoprotein P (SELENOP) is a major selenoenzyme in plasma and linked to antioxidant properties and possibly to lung cancer; however, supporting evidence is limited. We investigated the association between pre-diagnostic plasma SELENOP concentration and lung cancer risk in a case-control study of 403 cases and 403 individually matched controls nested within the Shanghai Men's Health Study. SELENOP concentration in pre-diagnostic plasma samples was measured by a sandwich enzyme-linked immunosorbent assay. Cases were diagnosed with lung cancer between 2003 and 2010. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI) for studying the association between plasma SELENOP concentration and lung cancer risk. Cases had slightly lower plasma SELENOP concentration than controls (4.3 ± 1.2 versus 4.4 ± 1.1 mg/l, P difference = 0.09). However, the multivariate analysis showed no association between plasma SELENOP concentration and lung cancer risk among all participants (OR = 1.08, 95% CI = 0.54-2.14 for quartile 4 versus quartile 1), or by smoking status or tumor aggressiveness. In contrast, although the number of cases was limited, plasma SELENOP concentration was positively associated with lung adenocarcinoma risk (OR = 5.38, 95% CI = 1.89-15.35 for tertile 3 versus tertile 1), but not with squamous cell lung carcinoma (OR = 1.69, 95% CI = 0.43-6.70). Our study of adult men living in selenium non-deficient areas in China provides little support for the inverse association between pre-diagnostic plasma SELENOP concentration and lung cancer risk. Our finding of a positive association with risk of lung adenocarcinoma needs to be interpreted with caution.

High Expression of S100A6 Predicts Unfavorable Prognosis of Lung Squamous Cell Cancer.

BACKGROUND S100 family of proteins is mainly involved in regulation of intracellular calcium homeostasis. Aberrant expression of S100 family members has been reported in many types of cancers. However, as a member of S100 family, the prognostic value of S100A6 for lung squamous cell carcinoma (SCC) has not been well-studied. MATERIAL AND METHODS Using immunohistochemistry, we investigated the expression of S100A6 in 177 patients with SCC and further divided the cohort into a high S100A6 expression group and a low S100A6 expression group. The chi-square test was applied to analyze the correlation between S100A6 expression and clinicopathological factors. Univariate analysis using the Kaplan-Meier method was performed to compare the difference in survival rates between the high S100A6 expression group and the low S100A6 expression group; multivariate analysis with Cox regression model was used to identify independent prognostic risk factors. RESULTS In our experiment, we demonstrated that the expression of S100A6 was significantly associated with patient age and tumor differentiation. High-expression of S100A6 was shown to be substantially related to the unfavorable prognosis of SCC. Moreover, our results confirmed that S100A6 was an independent risk factor for SCC prognosis, and could predict unfavorable prognosis. CONCLUSIONS High-expression of S100A6 was identified as an independent unfavorable prognostic factor for SCC, suggesting that targeting S100A6 may result in the development of potential targeted drug for SCC.

Inhibition of squamous cancer growth in a mouse model by Staphylococcal enterotoxin B-triggered Th9 cell expansion.

Currently, therapy for squamous cancer (SqC) is unsatisfactory. Staphylococcal enterotoxin B (SEB) has strong immune regulatory activity. This study tests the hypothesis that SEB enforces the effect of immunotherapy on SqC growth in a mouse model. C3H/HeN mice and the SqC cell line squamous cell carcinoma VII were used to create an SqC mouse model. Immune cell assessment was performed by flow cytometry. Real-time RT-PCR and western blotting were used to evaluate target molecule expression. An apoptosis assay was used to assess the suppressive effect of T helper-9 (Th9) cells on the SqC cells. The results showed that immunotherapy consisting of SEB plus SqC antigen significantly inhibited SqC growth in the mice. The frequency of Th9 cells was markedly increased in the SqC tissue and mouse spleens after treatment. SEB markedly increased the levels of signal transducer and activator of transcription 5 phosphorylation and the expression of histone deacetylase-1 (HDAC1) and PU.1 (the transcription factor of the interleukin 9 (IL-9) gene) in CD4+ T cells. Exposure to SqC-specific Th9 cells markedly induced SqC cell apoptosis both in vitro and in vivo. In conclusion, the administration of SEB induces Th9 cells in SqC-bearing mice, and theseTh9 cells inhibit SqC growth.

The blood-borne miRNA signature of lung cancer patients is independent of histology but influenced by metastases.

OBJECTIVES: In our previous studies we reported a panel of 24 miRNAs that allowed discrimination between blood of lung tumor patients independent of the histological subtype and blood of healthy controls with an accuracy of 95.4% [94.9%-95.9%]. Here, we now separately analyzed the miRNA expression in blood of non-small cell lung cancer (NSCLC), including squamous cell lung cancer and adenocarcinoma, and small cell lung cancer (SCLC) patients. PATIENTS AND METHODS: In total, we examined the expression levels of 1,205 miRNAs in blood samples from 20 patients from each of the three histological groups and determined differentially expressed miRNAs between histological subtypes and metastatic and non-metastatic lung cancer. We further determined the overlap of miRNAs expressed in each subgroup with the 24-miRNA signature of lung tumor patients. RESULTS: Based on a raw p-value < 0.05, only 18 blood-borne miRNAs were differentially expressed between patients with adenocarcinoma and with squamous cell lung carcinoma, 11 miRNAs between adenocarcinoma and SCLC, and 2 between squamous cell lung carcinoma and SCLC. Likewise, the comparison based on a fold change of 1.5 did not reveal major differences of the blood-borne miRNA expression pattern between NSCLC and SCLC. In addition, we found a large overlap between the blood-borne miRNAs detected in the three histological subgroups and the previously described 24-miRNA signature that separates lung cancer patients form controls. We identified several miRNAs that allowed differentiating between metastatic and non-metastatic tumors both in blood of patients with adenocarcinoma and in blood of patients with SCLC. CONCLUSION: There is a common miRNA expression pattern in blood of lung cancer patients that does not allow a reliable further subtyping into NSCLC or SCLC, or into adenocarcinoma and squamous cell lung cancer. The previously described 24-miRNA signature for lung cancer appears not primarily dependent on histological subtypes. However, metastatic adenocarcinoma and SCLC can be predicted with 75% accuracy.

Chemometric methods for studying the relationships between trace elements in laryngeal cancer and healthy tissues.

A quick and reliable method for the evaluation and classification of two types of tissues is presented. Several chemometric methods were applied to evaluate multivariate data of the tissue samples with respect to the content of trace elements. The content of Pb, Al, Zn, Cd, Cu, Ni and Co was determined in samples of healthy and cancerous tissue obtained from 26 patients. Determination was done at milligram/kilogram level with inductively coupled plasma optical emission spectrometry (ICP-OES) and atomic absorption spectroscopy (AAS) techniques. Contents of trace metals in studied tissues are not normally distributed; however, normal distribution was confirmed for log values. There is a statistically significant difference in the content of Zn, Cd, Cu and Al (p<0.01) and Ni and Co (p<0.05) when healthy tissue is compared to cancerous one. Correlation between contents of trace elements for studied tissues was positive; the highest was found between Zn and Cu. A chemometric methodology seems to be a promising tool for classifications of the tissue samples.

ABO blood groups in oral cancer: a first case-control study in a defined group of Iranian patients.

The ABO blood group has been recently proposed to influence development of oral cancer. The aim of this study was to evaluate the association between the type of ABO blood group and oral cancer. In a case-control study, 104 patients with oral cancer were compared with 90 blood donors without cancer as controls. Data regarding the patient demographics, blood groups, Rh status, cancer characteristics and oral habits were also compared between two subgroups of squamous and non-squamous oral cancers. For statistical analysis, Chi-square test, t-student Test and Logistic Regression were used to analyze the relationship between ABO blood groups and oral cancer. The frequency of blood group B was significantly higher in oral cancer patients than controls (32% vs 13%) (p value=0.01), but Rh factor did not show significant difference between cases and controls. According to Logistic Regression, people with blood group B and those older than 50 had 3.5 and 19.4 times elevated risk of developing oral cancer, respectively. The frequency of squamous cell cancer was also significantly higher in men and people older than 50. On the other hand, females, people under 50, and those with blood group B were at 5.6, 2.9 and 4.3 times higher risk of developing non-squamous cell oral cancer,respectively. People with blood group B are at a greater risk of developing oral cancer, and female patients under 50 years of age with blood group B have the highest risk to develop non-squamous cell oral cancer.

CYFRA21-1 as a serum tumor marker for follow-up patients with squamous cell lung carcinoma and oropharynx squamous cell carcinoma.

AIM: To evaluate serum soluble fragments of cytokeratin 19 (i.e., CYFRA21-1) as a tumor marker for patients with squamous cell lung carcinoma (SCLC) and oropharynx squamous cell carcinoma (OSCC). PATIENTS & METHODS: A total of 152 patients with SCLC and OSCC, and 84 control patients were included in the study. CYFRA21-1 concentration was measured using electrochemiluminescence immunoassays. RESULTS: As the disease stages increased, concentrations and sensitivity of CYFRA21-1 increased significantly in patients with SCLC and OSCC. A significant difference in sensitivity between the pretherapeutic group and recurrence group of OSCC (p = 0.001) was observed, as well as for SCLC (p = 0.024). A positive correlation (p = 0.042) existed between CYFRA21-1 concentrations and cancer stage of SCLC and OSCC. There was no significant correlation between CYFRA21-1 concentrations and different organ types with squamous cell cancer (p = 0.51). CONCLUSION: The CYFRA21-1 assay demonstrated a greater sensitivity for recurrent stages of SCLC and OSCC, and may prove beneficial in the prediction of SCLC and OSCC recurrence at an earlier date.

Prognostic value of interleukin-6 and interleukin-8 in laryngeal squamous cell cancer.

The aim of this study was to evaluate serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) as prognostic variables in patients with laryngeal squamous cell cancer. A total of 92 patients with primary diagnosis of laryngeal squamous cell cancer (LSCC), treated between 2003 and 2005, were included in this evaluation. Preoperative serum levels of IL-6 and IL-8 were measured by enzyme-linked immunosorbent assay methods. Results were compared according to clinical and pathological date criteria. Serum IL-6 and IL-8 levels were significantly higher in patients with LSCC compared to healthy controls (P < 0.0001). Serum IL-6 level was associated with lymph node metastasis (P < 0.001), T classification (P < 0.001) and clinical stage (P = 0.001). Multivariate analysis indicated that serum IL-6 was an independent predictor of LSCC-specific progression-free survival (P = 0.049) and overall survival (P = 0.040). Higher serum IL-6 level (IL-6 > 9.7 pg/ml) was associated with a shortened overall survival and progression-free survival (P < 0.05). Our data indicate that serum IL-6 is associated with the development and progression of LSCC. Serum IL-6 may serve as an independent prognostic marker for LSCC patients.

DNA repair gene expression level in peripheral blood and tumour tissue from non-small cell lung cancer and head and neck squamous cell cancer patients.

BACKGROUND: The nucleotide excision repair pathway is crucial for cellular DNA integrity and the ERCC1 helicase is also potentially involved in resistance to platinum-based chemotherapy, and high levels of ERCC1 mRNA in tumours have been associated with cisplatin resistance in different human cancers. The aim of this work was to investigate the correlation between DNA repair gene expression levels in tumour tissue, normal tissue and peripheral blood samples from patients with two common human cancers, non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (HNSCC), to test if blood gene expression could be a proxy for tumour tissue gene expression to predict response to platinum-based chemotherapy. METHODS: Using RT-qPCR we determined ERCC1, ERCC2, ERCC4, XPA, XPC, XRCC1, XRCC3, APEX, OGG1, MGMT mRNA levels in fresh NSCLC, normal lung and HNSCC tissue, as well as blood, from NSCLC and HNSCC patients who were treated surgically. RESULTS: Target gene expression in NSCLC and HNSCC tissue was higher than in blood. A statistically significant correlation (p<0.05) was found between target gene mRNA expression in tumour tissue and blood, in particular ERCC1, MGMT, XPC, XRCC1 and XRCC3 in NSCLC and APEX, ERCC1, ERCC2, ERCC4, XRCC1 and XRCC3 in HNSCC. CONCLUSIONS: The existence of a significant correlation between blood and tumour tissue expression of some genes of clinical interest, such as ERCC1 in NSCLC and HNSCC, could allow the introduction in clinical practice of a simple test that would measure mRNA levels of DNA repair genes in peripheral blood samples instead of tissue samples to determine prognostic and predictive factors in NSCLC and HNSCC patients.

Elevated progesterone receptor membrane component 1/sigma-2 receptor levels in lung tumors and plasma from lung cancer patients.

Cancer is one of the leading causes of death, and there is an urgent need for new biomarkers and therapeutic targets. The progesterone receptor membrane component 1 (Pgrmc1) protein is upregulated in multiple types of cancer, and Pgrmc1 is required for tumor cell proliferation, motility and tumor formation in vivo. Furthermore, a small molecule inhibitor of Pgrmc1 suppressed the growth of lung, breast and cervical cancer cell lines. Recently, Pgrmc1 was identified as the sigma-2 receptor, a putative type of opioid receptor, and sigma-2 receptors are induced in cancers. However, Pgrmc1 shares no homology with known opioid or hormone receptors but is related to cytochrome b(5), and Pgrmc1 binds to heme and has reducing activity. In this study, we have analyzed Pgrmc1 levels in clinical tumor samples from squamous cell lung cancers (SCLC) and lung adenocarcinomas compared to corresponding nonmalignant tissue. Pgrmc1 levels increased significantly (p ≤ 0.05) in 12/15 SCLC samples and was elevated in poorly differentiated tumors. Pgrmc1 was highly expressed in SCLC cell lines, and SCLC cell survival was inhibited by siRNA knockdown of Pgrmc1 or the Pgrmc1 inhibitor AG-205. In adenocarcinomas, 6/15 tumors significantly had elevated Pgrmc1 levels, which correlated with patient survival. Pgrmc1 localizes to secretory vesicles in cancer cells, and Pgrmc1 was secreted by lung cancer cells. Furthermore, Pgrmc1 was significantly elevated in the plasma of lung cancer patients compared to noncancer patients. Together, the results demonstrate that Pgrmc1 is a potential tumor and serum biomarker, as well as a therapeutic target, for lung cancer.

Change of telomerase activity in peripheral whole blood of head and neck squamous cell carcinoma patients before and after surgery: a pilot study.

BACKGROUND The purpose of this study was to evaluate telomerase activity in peripheral whole blood from head and neck squamous cell carcinoma (HNSCC) patients as a biomarker for diagnosis of HNSCC or detection of recurrence during follow-up. MATERIALS AND METHODS Telomerase activity was measured from peripheral whole blood extracts by telomerase repeat amplification protocol (TRAP) in HNSCC patients before and after surgery and in a control group. Sixty-two HNSCC patients and 42 control subjects were included. RESULTS Telomerase activity was found in 41 out of 62 (66.1%) HNSCC patients before surgery and in 8 out of 42 (19.0%) controls (p<0.001). Among 41 HNSCC patients who showed positive telomerase activity before surgery, 32 (78.1%) showed a conversion of telomerase activity to negative after surgery. In follow-up, 6 out of 8 (75%) showed conversion of telomerase activity from negative to positive after recurrence. Telomerase activity was changed to negative in 4 out of 6 (66%) recurred patients with positive telomerase activity after second surgery. CONCLUSION The telomerase activity in peripheral whole blood extracts of HNSCC patients might be a useful biomarker for detecting recurrence after treatment. Further study with larger sample size using a more sensitive detection method of telomerase activity is necessary to verify these results.

MicroRNA involvement in esophageal carcinogenesis.

MicroRNAs (miRs) have recently emerged as a novel class of gene expression regulators. The number of studies documenting an altered miR expression pattern in cancer continues to expand rapidly. Critical information is continuously gained regarding how aberrantly expressed miRs contribute to carcinogenesis. Current studies provide evidence that analyses of miR expression patterns have potential clinical applications toward developing tumor biomarkers to identify the presence and dissemination of esophageal cancer, as well as to assess tumor chemosensitivity or radiosensitivity. The incidence of esophageal cancer is on the rise, and this disease continues to portend a poor prognosis. The current review addresses ways in which altered miR expression contributes to esophageal carcinogenesis, along with how recent discoveries may be applied clinically.

Change of telomerase activity in peripheral whole blood of head and neck squamous cell carcinoma patients before and after surgery: a pilot study

BACKGROUND The purpose of this study was to evaluate telomerase activity in peripheral whole blood from head and neck squamous cell carcinoma (HNSCC) patients as a biomarker for diagnosis of HNSCC or detection of recurrence during follow-up. MATERIALS AND METHODS Telomerase activity was measured from peripheral whole blood extracts by telomerase repeat amplification protocol (TRAP) in HNSCC patients before and after surgery and in a control group. Sixty-two HNSCC patients and 42 control subjects were included. RESULTS Telomerase activity was found in 41 out of 62 (66.1%) HNSCC patients before surgery and in 8 out of 42 (19.0%) controls (p<0.001). Among 41 HNSCC patients who showed positive telomerase activity before surgery, 32 (78.1%) showed a conversion of telomerase activity to negative after surgery. In follow-up, 6 out of 8 (75%) showed conversion of telomerase activity from negative to positive after recurrence. Telomerase activity was changed to negative in 4 out of 6 (66%) recurred patients with positive telomerase activity after second surgery. CONCLUSION The telomerase activity in peripheral whole blood extracts of HNSCC patients might be a useful biomarker for detecting recurrence after treatment. Further study with larger sample size using a more sensitive detection method of telomerase activity is necessary to verify these results (AU)

Fucosylated glycoproteomic approach to identify a complement component 9 associated with squamous cell lung cancer (SQLC).

Human lung cancer is a major cause of cancer mortality worldwide. Understanding the pathophysiological features and the development of novel biomarkers for diagnosis as well as treatment are major tasks. In the present study, sera from ten SQLC patients and healthy control (HEC) were collected and pooled, respectively. The pooled sera were depleted via an immunoaffinity method and further subjected to fucosylation enrichment. Enriched fucosylated glycoproteins were resolved by SDS-PAGE and subsequently analyzed by LC-ESI-MS/MS. From comparative proteomic analysis, we selected the C9 protein. C9 protein levels were validated by Western blot, protein arrays and the fucosylation levels of C9 by hybrid lectin ELISA (HLE) in the sera of 120 HEC and 118 SQLC patients. The C9 protein level was 6.4-fold higher in SQLC patients compared to HEC, as determined by Western blot analysis. The results were concurrently confirmed by a protein array that showed a C9 level significantly higher in SQLC patients, as compared to HEC, with a sensitivity of 53% and a specificity of 89%. C9 fucosylation levels were significantly higher in SQLC patients compared to HEC (p<0.05) when tested by HLE. These findings suggest that C9 and fucosylated form could serve as a useful marker for SQLC.

CD44 as a stem cell marker in head and neck squamous cell carcinoma.

In the recent past, evidence is increasing indicating the existence of a subpopulation of resistant tumor cells in head and neck squamous cell carcinoma (HNSCC) that cannot be eradicated by established antineoplastic treatments. These cancer stem cells (CSCs) have features of somatic stem cells such as selfrenewal, proliferation and differentiation. CD44+ cells in tumors of the head and neck are referred to as CSCs of HNSCC. Expression profiling of CD44 in 29 HNSCC tumors was performed by fluorescence microscopy. ELISA analysis was performed to detect concentration of soluble CD44 in the peripheral blood of 29 HNSCC patients and 11 healthy controls. Expression of CD44 was determined in all HNSCC tissue samples (n=29). In all samples a surface staining pattern was found. The concentration of CD44 in the peripheral blood of HNSCC patients was significantly higher compared to a healthy control group (mHNSCC =13.5 ± 0.5 ng/ ml; mCont = 9.3 ± 0.6 ng/ml; P=0.6 x 10(-12)). The role of CD44 as a marker for CSCs in HNSCC remains to be ascertained. Further experiments might reveal its role as a diagnostic and prognostic factor, and possibly as a therapeutic target.

A label-free biosensor based on silver nanoparticles array for clinical detection of serum p53 in head and neck squamous cell carcinoma.

By using triangular silver (Ag) nanoparticle array, a localized surface plasmon resonance (LSPR) nanosensor was fabricated and shown to sense serum p53 protein in vitro, which is involved in head and neck squamous cell carcinoma (HNSCC). The nanosensor consists of a triangular Ag nanoparticles array with single particle dimension of 120 nm in-plane width and 45 nm out-of-plane height. When examined using LSPR nanobiosensor, the results indicated significant difference in LSPR shifts (Δλ(max)) between HNSCC patient and control. Although there is need for precise quantification and large-scale prospective, this report shows that the LSPR nanobiosensor provides a promising platform with attractive advantages for serological diagnosis or molecular diagnosis in tumor, such as HNSCC. This is the first clinical application of the LSPR nanosensor in HNSCC.