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Statistical process of grouping and modeling

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Purpose: Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Squamous cell carcinoma (SCC) is one major subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCC patients.Experimental Design: MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I–III), who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined.Results: We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34 patients) and 96.2% in a test cohort (26 patients). We also showed that high expression of hsa-miR-31 was associated with poor survival in these 60 SCC patients by Kaplan–Meier analysis (P = 0.007), by univariate Cox analysis (P = 0.011), and by multivariate Cox analysis (P = 0.011). This association was independently validated in a separate cohort of 88 SCC patients (P = 0.008, 0.011, and 0.003 in Kaplan–Meier analysis, univariate Cox analysis, and multivariate Cox analysis, respectively). We then determined that the tumor suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2.Conclusions: Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31. Clin Cancer Res; 17(21); 6802–11. ©2011 AACR.

Purpose: Effective biomarkers for the diagnosis of non–small cell lung cancer (NSCLC) are needed. We previously showed that isocitrate dehydrogenase 1 (IDH1) is significantly increased in NSCLC tumors. This study aimed to examine the plasma levels of IDH1 in a large patient population to evaluate its effectiveness in NSCLC diagnosis.Experimental Design: The plasma levels of IDH1, CA125, Cyfra21-1, and CEA were assayed by ELISA. Blood samples were obtained from 1,422 participants (943 patients with NSCLC and 479 healthy controls). The samples were randomly divided into a training set and a test set. Receiver operating characteristic and binary logistic regression analyses were applied to evaluate diagnostic efficacy and establish diagnostic mathematical models.Results: Plasma IDH1 levels were significantly higher in patients with NSCLCs than in healthy controls (P < 0.001). The diagnostic use of IDH1 in lung adenocarcinoma [area under curve (AUC): 0.858 and 0.810; sensitivity: 77.1% and 76.2%; specificity: 82.9% and 76.6%; in the training set and test set, respectively] was significantly greater than that of CA125, Cyfra21-1, or CEA (P < 0.001). The model combining IDH1 with CEA, CA125, and Cyfra21-1 was more effective for lung adenocarcinoma diagnosis than IDH1 alone (sensitivity and specificity in the training set: 75.8%, 89.6%; test set: 86.3%, 70.7%). In addition, the plasma levels of IDH1 could contribute to the diagnostic model of lung squamous cell carcinoma.Conclusions: IDH1 can be used as a plasma biomarker for the diagnosis of NSCLCs, particularly lung adenocarcinoma, with relatively high sensitivity and specificity. Clin Cancer Res; 19(18); 5136–45. ©2013 AACR.

The diagnostic effect of IDH1 after stratification in smokers and non-smokers.

Figure S1. IDH1 concentrations in patients with different T stages. (A) IDH1 concentrations in ADC patients with stages T1a-T2a versus stages T2b-T4. (B) IDH1 concentrations in SCC patients with stages T1a-T2a versus stages T2b-T4.

Background The function of LINC00501, a long-non-coding RNA (lncRNA), is unclear at present. According to the Cancer Genome Atlas (TCGA), LINC00501 is highly expressed in lung cancer (LC), but whether it can be adopted as a potential therapy target for LC still needs further research. Methods The expression of LINC00501 in LC was analyzed based on the TCGA, and a real-time fluorescent quantitative PCR assay was carried out to quantify LINC00501 in non-small-cell lung cancer (NSCLC). Additionally, bioinformatics analysis, luciferase reporter gene technique, and RNA immunoprecipitation (RIP) were employed to analyze the direct interaction between LINC00501 and miR-129-5p, and CCK-8 and Transwell assays and flow cytometry were employed to analyze the effects of LINC00501 on cell proliferation, invasion, and apoptosis. Furthermore, a Western blot assay was carried out to determine the protein level of HMGB1. Results LINC00501 was highly expressed in LC according to the database, and it was found that LINC00501 was upregulated in NSCLC specimens and cells, and the up-regulation indicated an unfavorable prognosis. Besides, knockdown of LINC00501 hindered the proliferation and invasion of NSCLC cells and intensified their apoptosis, and LINC00501 could be adopted as competitive endogenous RNA to regulate HMGB1 and tumorigenesis through miR-129-5p. Conclusion LINC00501 is overexpressed in LC and the overexpression indicates poor prognosis of patients. In addition, LINC00501 can inhibit the invasion and migration of LC by mediating miR-129-5p/HMGB1.

Understanding the key factor controlling phase transitions of correlated oxides by chemical doping is becoming of fundamental and technological interest. Here, we report vanadium chain symmetry as an effective means of mediating the structural phase transition (SPT) temperature in hydrothermal Cr-doped VO2. In-situ X-ray absorption fine structure spectroscopy unveils that high structural symmetry with equidistant 2.93 A V–V zigzag chains, along with the dimerized V–V straight chain induced by Cr-doping, can stabilize VO2 at elevated temperature, thus raising the critical temperature of the VO2 phase transition. The Cr-doped VO2 system exhibited a SPT process involving lattice expansion, accompanied by V–V chain reconstruction into the rutile phase. These findings provide novel insights and guidance in chemically tailoring the phase transition of VO2.

The purpose of this study is to investigate the impact of positive cancer/lung cancer family history (FH) on clinical features and outcome in non-small cell lung cancer (NSCLC) patients. We analyzed 4,491 NSCLC patients with NSCLC who presented from January 1999-December 2005. Chi-square test and Wilcoxon test were used for univariate comparisons, while Cox Proportional Hazards regression analysis was performed to evaluate the adjusted risk of death. Univariate probability of survival was calculated using Kaplan-Meier estimate and compared using the log-rank test. Of 4,491 patients, 579 patients (12.89%) had positive FH, including 233 patients (5.19%) with FH of lung cancer. Patients with positive lung cancer FH, compared to those with negative FH, were diagnosed at earlier age (57 vs. 60; P 0.001), presented more cases of adenocarcinoma (58.80 vs. 50.69%; P = 0.016), and at more advanced stage (Stage IIIB/IV 45.74 vs. 36.79%; P 0.001). These differences were also detected in patients with positive cancer FH. In addition, more females and non-smokers were among patients with positive cancer FH (30.05 vs. 26.15%; P = 0.045 and 39.90 vs. 33.82%; P = 0.008, respectively). Furthermore, patients with advanced cancer (stage IIIB/IV) who had positive FH had lower response rate to chemotherapy (CRPR 24.68 vs. 34.42%; P = 0.024). Nevertheless, patients with positive lung cancer FH had better prognosis (P = 0.015), especially if diagnosed at an early stage (P = 0.035), and their adjusted relative risk of death was lower (RR 0.69; 95% CI: 0.51-0.93; P = 0.015). Definite epidemiologic and survival differences exist between NSCLC patients with positive or negative FH of cancer. Our results suggest that cancer FH is an important factor of clinical features, and could serve as a prognostic indicator for NSCLC.

Lung cancer remains the most common cause of death for malignancy in both men and women. Current therapies for NSCLC patients are inefficient due to the lack of diagnostic and therapeutic markers. The phospho-Ser/Thr-Pro specific prolyl-isomerase Pin1 is overexpressed in many different cancers, including NSCLC, and may possibly be used as a target for cancer therapy. We identified 79 cases with the follow-up survival and investigated the clinical relevance of Pin1 expression in NSCLC patients. To validate the oncogenic potential of Pin1 in lung cells, we overexpressed Pin1 in Glc82 cells, and downregulated Pin1 by RNA interference in H1299 cells. The 5-year survival rate of the 79 patients was 54.6%. High expression of Pin1 correlated with poor survival by univariate analysis as well as by multivariate analysis, demonstrating that high expression of Pin1 was an independent prognostic factor. Consistent with the clinical findings, overexpression of Pin1 in Glc82 cells increased cell growth and colony formation and tumorigenicity in nude mice including cell migration, invasion. To further validate the role of Pin1 in lung cancer carcinogenesis, lentivirus-mediated siRNA targeting of Pin1 resulted in the stable suppression of both cell growth, anchorage-independent growth in soft agar and tumorigenic including cell migration, invasion in H1299 cells. Pin1 expression may be an unfavorable prognostic factor in patients of NSCLC patients, and these results indicate that Pin1 may have a role in tumor development and metastasis and thus could serve as a novel target for treatment of NSCLC.

Purpose: Effective biomarkers for the diagnosis of non–small cell lung cancer (NSCLC) are needed. We previously showed that isocitrate dehydrogenase 1 (IDH1) is significantly increased in NSCLC tumors. This study aimed to examine the plasma levels of IDH1 in a large patient population to evaluate its effectiveness in NSCLC diagnosis. Experimental Design: The plasma levels of IDH1, CA125, Cyfra21-1, and CEA were assayed by ELISA. Blood samples were obtained from 1,422 participants (943 patients with NSCLC and 479 healthy controls). The samples were randomly divided into a training set and a test set. Receiver operating characteristic and binary logistic regression analyses were applied to evaluate diagnostic efficacy and establish diagnostic mathematical models. Results: Plasma IDH1 levels were significantly higher in patients with NSCLCs than in healthy controls (P < 0.001). The diagnostic use of IDH1 in lung adenocarcinoma [area under curve (AUC): 0.858 and 0.810; sensitivity: 77.1% and 76.2%; specificity: 82.9% and 76.6%; in the training set and test set, respectively] was significantly greater than that of CA125, Cyfra21-1, or CEA (P < 0.001). The model combining IDH1 with CEA, CA125, and Cyfra21-1 was more effective for lung adenocarcinoma diagnosis than IDH1 alone (sensitivity and specificity in the training set: 75.8%, 89.6%; test set: 86.3%, 70.7%). In addition, the plasma levels of IDH1 could contribute to the diagnostic model of lung squamous cell carcinoma. Conclusions: IDH1 can be used as a plasma biomarker for the diagnosis of NSCLCs, particularly lung adenocarcinoma, with relatively high sensitivity and specificity. Clin Cancer Res; 19(18); 5136–45. ©2013 AACR.

Biomarker identification is crucial for the selection of patients who might benefit from radiotherapy. To explore potential markers for response and prognosis in patients with locally advanced esophageal carcinoma treated with radiotherapy followed by surgery, we evaluated the expression of cell cycle checkpoint-related proteins Chk2, Cdc25C, and Cyclin D1. A total of 56 patients with locally advanced esophageal squamous cell carcinoma were treated with radiotherapy followed by surgery. Pretreatment tumor biopsy specimens were analyzed for Chk2, Cdc25C, and Cyclin D1 expression by immunohistochemistry. High expression of Chk2, Cyclin D1, and Cdc25C was observed in 44 (78.6%), 15 (26.8%), and 27 (48.2%) patients, respectively. The median survival was 16 months (range, 3–154 months), with a 5-year overall survival rate of 19.6%. Overexpression of Chk2 was associated with smoking (P = 0.021), overexpression of Cdc25C was associated with patient age (P = 0.033) and tumor length (P = 0.001), and overexpression of Cdc25C was associated with pathologic complete response (P = 0.038). Univariate analysis demonstrated that overexpression of Cdc25C and pathologic complete response was associated with better survival. In multivariate analysis, Cdc25C was the most significant independent predictor of better survival (P = 0.014) for patients treated with radiotherapy followed by surgery. Overexpression of Cdc25C was significantly associated with pathologic complete response and better survival of patients with locally advanced esophageal cancer treated with radiotherapy followed by surgery. These results suggest that Cdc25C may be a biomarker of treatment response and good prognosis for esophageal carcinoma patients. Thus, immunohistochemical staining of Cdc25C in a pretreatment specimen may be a useful method of identifying optimal treatment for patients with esophageal carcinoma.

Distributed multimedia-based surveillance has been widely used for monitoring and control systems as well as many other industry applications. These applications enable various multimedia sources to be transported, processed, and visualized. Of many requirements of these systems, real-time and high reliability are often required and proved to be challenging. In this paper, we presented an IP-based architecture for implementing large-scale distributed video surveillance systems with real-time, synchronized visualization, and high reliability requirements. The main contribution of our work is the dynamical flow control mechanism integrated with fault-tolerant system architecture to improving real-time performance and system reliability on top of an inherently unreliable IP network. Experiments with large systems are also discussed.

Recently, microRNA-99 family members, such as miR-99a/b and miR-100, have been reported to exhibit abnormal expression in various malignant tumors, but their functions in carcinomas are controversial. In this study, we focused on miR-99a and miR-100, which were determined to be universally downregulated in esophageal squamous cell carcinoma, and investigated their functions and potential mechanisms of action. The downregulation of miR-99a/100 was validated by qRT-PCR in 101 ESCC surgical tissue samples and in 3 ESCC cell lines. The overexpression of miR-99a and miR-100 via the transient transfection of the corresponding precursor molecules inhibited cell proliferation by inducing apoptosis in the ESCC cell lines. To investigate the molecular mechanism of miR-99a/100-induced apoptosis, luciferase reporter assays and Western blots were performed to demonstrate that the overexpression of miR-99a/100 suppressed the expression of mTOR by directly targeting its 3'UTR in a post-transcriptional manner. Clinically, the decreased expression of miR-99a/100 was associated with worse overall survival in ESCC patients. In conclusion, these results indicated that miR-99a and miR-100 inhibited cell proliferation by suppressing mTOR in ESCC cell lines, and therefore, the miR-99a/100-mTOR signaling pathway is a potential therapeutic target for inducing apoptosis to combat ESCC.

Doping VO(2) with tungsten can lower the metal-insulator transition (MIT) temperature and thus provide a controlled means for tailoring the MIT properties of VO(2) materials. Here, infrared spectroscopy has been employed as a tool for identifying structural changes in doped VO(2) as a way of lowering the MIT temperature.

Understanding the mechanism of W-doping induced reduction of critical temperature (T(C)) for VO(2) metal-insulator transition (MIT) is crucial for both fundamental study and technological application. Here, using synchrotron radiation X-ray absorption spectroscopy combined with first-principles calculations, we unveil the atomic structure evolutions of W dopant and its role in tailoring the T(C) of VO(2) MIT. We find that the local structure around W atom is intrinsically symmetric with a tetragonal-like structure, exhibiting a concentration-dependent evolution involving the initial distortion, further repulsion, and final stabilization due to the strong interaction between doped W atoms and VO(2) lattices across the MIT. These results directly give the experimental evidence that the symmetric W core drives the detwisting of the nearby asymmetric monoclinic VO(2) lattice to form rutile-like VO(2) nuclei, and the propagations of these W-encampassed nuclei through the matrix lower the thermal energy barrier for phase transition.

MicroRNAs (miRNAs) as a species of small non coding single stranded RNA of about 21-25 nucleotides have important roles in the development of different cancers. In present study, we found that the expression of miR-25 was up-regulated in 60 esophageal squamous cell carcinoma (ESCC) tissues compared with matched adjacent non-cancer tissues. Moreover, we demonstrated that the up-regulation of miR-25 was significantly correlated with the status of lymph node metastasis and TNM (Tumor, Node and Metastasis) stage. Furthermore, over-expression of miR-25 markedly promoted migration and invasion of ESCC cells. On the contrary, down-regulation of miR-25 inhibited the migration and invasion of cells. E-cadherin(CDH1) is a very important tumor metastasis suppressor. We further identified that miR-25 directly targeted CDH1 3'-untranslated region (3'UTR) and repressed the expression of CDH1. These results, for the first time, demonstrate that miR-25 promotes ESCC cell migration and invasion by suppressing CDH1 expression.

Purpose: Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Squamous cell carcinoma (SCC) is one major subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCC patients. Experimental Design: MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I–III), who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined. Results: We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34 patients) and 96.2% in a test cohort (26 patients). We also showed that high expression of hsa-miR-31 was associated with poor survival in these 60 SCC patients by Kaplan–Meier analysis (P = 0.007), by univariate Cox analysis (P = 0.011), and by multivariate Cox analysis (P = 0.011). This association was independently validated in a separate cohort of 88 SCC patients (P = 0.008, 0.011, and 0.003 in Kaplan–Meier analysis, univariate Cox analysis, and multivariate Cox analysis, respectively). We then determined that the tumor suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2. Conclusions: Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31. Clin Cancer Res; 17(21); 6802–11. ©2011 AACR.

Cyclin E is reported to be an important cell cycle regulator, and its dysregulation is implicated in tumorigenesis including esophageal squamous cell carcinoma (ESCC). MicroRNAs (miRNAs) regulate gene expression at the posttranscriptional level and play important roles in tumor initiation and progression. However, the regulation of cyclin E by miRNAs is still unclear in ESCC. In the present study, we found that overexpression of miR-29c inhibited cyclin E expression by targeting 3' untranslated region of cyclin E messenger RNA in ESCC cells. Moreover, overexpression of miR-29c induced cell cycle G(1)/G(0) arrest through suppression of cyclin E expression, without affecting other G(1) phase-related proteins level, such as cyclin D1, cyclin D2, cyclin dependent kinase (CDK) 2 and CDK6. Furthermore, we demonstrated that overexpression of miR-29c inhibited proliferation of ESCC cells in vitro and in vivo. In addition, we detected miR-29c expression in 26 pairs of esophageal tumor-in-site-tissues and 60 pairs of ESCC tissues. The result showed that miR-29c level significantly decreased in ESCC tumor tissues and cell lines compared with normal esophageal epithelia. Taken together, our findings indicated that miR-29c was frequently downregulated in ESCC tissues and cells and suppressed tumor growth by inducing cell cycle G(1)/G(0) arrest mainly through modulating cyclin E expression.

Lung cancer is the leading cause of cancer-related death in the world and approximately 30-40% of patients with stage Ⅰ non-small cell lung cancer (NSCLC) die of recurrent disease. miRNA expression profiles can be diagnostic and prognostic markers of lung cancer. Recently, miR-34 family has been shown to be part of the p53 pathway which is frequently involved in lung cancer, and the expression of miR-34 has been reported to be regulated by DNA methylation. In present study, we investigated the correlation between DNA methylation status of miR-34 family and recurrence of stage Ⅰ NSCLC patients. miR-34a and miR-34b/c promoter methylation status were determined by nested methylation-specific PCR in FFPE tumor tissues from 161 patients of stage Ⅰ NSCLC. Furthermore, mature miR-34b and miR-34c expression were analyzed by qRT-PCR in the same panel tissues. Our results revealed that aberrant DNA methylation of miR-34b/c was correlated with a high probability of recurrence (p = 0.026) and associated with poor overall survival (p = 0.010) and disease-free survival (p = 0.017). No significant association was found for miR-34a methylation. Multivariate analysis showed that promoter hypermethylation of miR-34b/c was an independent prognostic factor of stage Ⅰ NSCLC. Moreover, no significant association between mature miR-34b and miR-34c expression and DNA methylation status was found. In conclusion, we have identified promoter hypermethylation of miR-34b/c as a relatively common event in NSCLC and might be a potential prognostic factor for stage Ⅰ NSCLC.

Nuclear factor of activated T cells (NFAT) is an important family of transcription factors that can be activated by calmodulin and calcineurin in human cells. To investigate the expression and clinical significance of NFAT isoforms and calcineurin in non-small cell lung cancer (NSCLC), we collected tumor and adjacent normal tissues from 159 NSCLC patients and assembled them in a tissue microarray. Protein levels of NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin were determined using immunohistochemistry. Correlations between NFAT and calcineurin expression and clinicopathologic characteristics were analyzed. We found that the positive rates of NFAT1 (52.8%, 84/159), NFAT2 (11.3%, 18/159), NFAT3 (28.3%, 45/ 159), NFAT4 (47.2%, 75/159), and calcineurin (47.8%, 76/159) expression were significantly higher in tumor tissues than in adjacent normal lung tissues (P < 0.001), respectively. The positive rate of NFAT1 expression was significantly higher in patients with adenocarcinoma (63.5%, 47/74) than in those with squamous cell carcinoma (43.5%, 37/85) (χ2 = 6.340, P = 0.012); with lymph node metastasis (61.6%, 53/ 86) than without lymph node metastasis (42.5%, 31/73) (χ2 = 5.818, P = 0.016); and with stage-ll and -III diseases (61.8%, 55/89) than with stage-I disease (41.4%, 29/70) (χ2 = 6.524, P = 0.011). Moreover, the overexpression of NFAT1 was associated with poor survival of NSCLC patients (χ2 = 5.006, P = 0.025). The positive rate of NFAT4 was significantly higher in patients with squamous carcinoma (57.6%, 49/85) than in those with adenocarcinoma (35.1%, 26/74) (χ2 = 8.045, P = 0.005) and with high and moderate differentiation (54.9%, 61/111) than with low differentiation (29.2%, 14/48) (χ2 = 8.943, P = 0.003). Calcineurin overexpression was significantly associated with histologic type (higher in squamous carcinoma than in adenocarcinoma, χ2 = 8.897, P = 0.003), differentiation grade (higher in high-moderation grade than in low grade, χ2 = 9.566, P = 0.002) and gender (higher in male than in female, χ2 = 5.766, P = 0.016). Furthermore, calcineurin expression was significantly correlated with NFAT4 level (r = 0.429, P < 0.001). These results suggest that NFAT1 expression is associated with lung adenocarcinoma progression, and NFAT4 expression, which was higher in squamous lung cancer, is associated with calcineurin expression and differentiation grade.

microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. Recently, we examined the global miRNA expression profile of esophageal squamous cell carcinoma (ESCC) and demonstrated that miR-92a was highly expressed in tumor tissues. In this study, we found that the up-regulation of miR-92a was significantly correlated with the status of lymph node metastasis and TNM stage in 107 ESCC patients. Moreover, the up-regulation of miR-92a was associated with poor survival of ESCC patients and might be used as an independent prognostic factor. Next, we investigated the role and mechanism of miR-92a in ESCC cells, and found that miR-92a modulated the migration and invasion but not apoptosis and proliferation of ESCC cells in vitro. We further demonstrated that miR-92a directly targeted the CDH1 3′-UTR and repressed the expression of CDH1, a tumor metastasis suppressor. In addition, restoring of miR-92a-resistant CDH1 expression in miR-92a-overexpression cells recovered the pro-metastasis activity of miR-92a. Taken together, we demonstrated that miR-92a promotes ESCC cell migration and invasion at least partially via suppression of CDH1 expression, and patients with up-regulated miR-92a are prone to lymph node metastasis and thus have poor prognosis.

Oesophageal cancer is one of the most common cancers worldwide. Currently, the tumour, node, metastasis (TNM) staging system is the primary method for determining its extent and prognosis, however, data suggest this system does not predict prognosis accurately. Research has, therefore, concentrated on searching for specific biomarkers. Paxillin has been shown to play an important role in controlling cell spread and migration. Its over-expression is considered to correlate with the prognosis of some types of cancers, however, the relationship between paxillin expression and clinical outcome in oesophageal cancer has not been investigated. This study determined the expression of paxillin by immunohistochemistry on the tissue microarray of 100 oesophageal squamous cell cancer patients followed up for a mean of 55 months. Paxillin was over-expressed in tumours in 27/100 cases, compared with 6/100 cases for adjacent non-tumoural cells. No correlation occurred between expression of paxillin and overall patient survival, hence paxillin is not an effective prognostic marker in these patients.

Increasing evidence has suggested that RhoE plays an important role in carcinogenesis and progression. However, the correlation between RhoE expression and clinical outcome in lung cancer has not been investigated. RhoE expression was detected by immunohistochemistry on tissue microarray containing samples from 115 patients with non–small cell lung cancer with a median follow-up of 54 months. RhoE was overexpressed in the cytoplasm of lung cancer cells compared with undetectable expression of RhoE in the adjacent nontumoral cells. Patients with RhoE-negative tumors had substantially longer cancer-related survival than did patients with RhoE-positive tumors. Multivariate analysis showed that RhoE overexpression was an independent marker for cancer-related survival in the entire population after adjusting for other prognostic factors. RhoE expression may serve as an unfavorable prognostic factor in patients with non–small cell lung cancer.

Lung cancer is the leading cause of cancer-related death in the world. To explore tumor biomarkers for clinical application, two-dimensional fluorescence difference gel electrophoresis and subsequent MALDI-TOF/TOF mass spectrometry were performed to identify proteins differentially expressed in 12 pairs of lung squamous cell tumors and their corresponding normal tissues. A total of 28 nonredundant proteins were identified with significant alteration in lung tumors. The up-regulation of isocitrate dehydrogenase 1 (IDH1), superoxide dismutase 2, 14-3-3ε, and receptor of activated protein kinase C1 and the down-regulation of peroxiredoxin 2 in tumors were validated by RT-PCR and Western blot analysis in independent 15 pairs of samples. Increased IDH1 expression was further verified by the immunohistochemical study in extended 73 squamous cell carcinoma and 64 adenocarcinoma clinical samples. A correlation between IDH1 expression and poor overall survival of non-small cell lung cancer (NSCLC) patients was observed. Furthermore, ELISA analysis showed that the plasma level of IDH1 was significantly elevated in NSCLC patients compared with benign lung disease patients and healthy individuals. In addition, knockdown of IDH1 by RNA interference suppressed the proliferation of NSCLC cell line and decreased the growth of xenograft tumors in vivo. These observations suggested that IDH1, as a protein promoting tumor growth, could be used as a plasma biomarker for diagnosis and a histochemical biomarker for prognosis prediction of NSCLC.

Nanoscale materials with size smaller than the characteristic domain size could simplify the domain structure and uncover the intrinsic properties in detail. Herein, a ultrafast open space calcination pathway is first put forward to synthesize high-quality single-domain VO(2)(M) nanocrystals and an in situ variable-temperature IR spectroscopy is first proposed to identify the size-dependent MIT behaviors in VO(2)(M) below single-domain size. The variable-temperature IR spectroscopy clearly reveals that these single-domain VO(2)(M) nanocrystals exhibit new size-dependent MIT behaviors, while the IR analysis further suggests that the size-related defect density and scattering efficiency could be used to account for their novel size-dependent MIT behaviors. This new characterization strategy of in situ variable-temperature IR spectroscopy holds great promise for extending to other systems to gain valuable insight into their intrinsic phase transition behaviors. Also, this ultrafast open space calcination pathway sets forth a new avenue in fabricating high-quality functional nanocrystals and paves the way for constructing intelligent nanodevices in the near future.