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About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19-25 nt and play important roles in gene regulation in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis of stage I NSCLC. MiRNAs extracted from 527 stage I NSCLC patients were profiled on the human miRNA expression profiling v2 panel (Illumina). The expression profiles were analyzed for their association with cancer subtypes, lung cancer brain metastasis and recurrence/relapse free survival (RFS). MiRNA expression patterns between lung adenocarcinoma and squamous cell carcinoma differed significantly with 171 miRNAs, including Let-7 family members and miR-205. Ten miRNAs associated with brain metastasis were identified including miR-145*, which inhibit cell invasion and metastasis. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 34 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype, whereas the second containing 27 miRNAs was adenocarcinoma specific. Both signatures were validated using formalin-fixed paraffin embedded and/or fresh frozen tissues in independent data set with 170 stage I patients. Our findings have important prognostic or therapeutic implications for the management of stage I lung cancer patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease.

BackgroundMicroarray technology enables a standardized, objective assessment of oncological diagnosis and prognosis. However, such studies are typically specific to certain cancer types, and the results have limited use due to inadequate validation in large patient cohorts. Discovery of genes commonly regulated in cancer may have an important implication in understanding the common molecular mechanism of cancer.Methods and FindingsWe described an integrated gene-expression analysis of 2,186 samples from 39 studies to identify and validate a cancer type-independent gene signature that can identify cancer patients for a wide variety of human malignancies. The commonness of gene expression in 20 types of common cancer was assessed in 20 training datasets. The discriminative power of a signature defined by these common cancer genes was evaluated in the other 19 independent datasets including novel cancer types. QRT-PCR and tissue microarray were used to validate commonly regulated genes in multiple cancer types. We identified 187 genes dysregulated in nearly all cancerous tissue samples. The 187-gene signature can robustly predict cancer versus normal status for a wide variety of human malignancies with an overall accuracy of 92.6%. We further refined our signature to 28 genes confirmed by QRT-PCR. The refined signature still achieved 80% accuracy of classifying samples from mixed cancer types. This signature performs well in the prediction of novel cancer types that were not represented in training datasets. We also identified three biological pathways including glycolysis, cell cycle checkpoint II and plk3 pathways in which most genes are systematically up-regulated in many types of cancer.ConclusionsThe identified signature has captured essential transcriptional features of neoplastic transformation and progression in general. These findings will help to elucidate the common molecular mechanism of cancer, and provide new insights into cancer diagnostics, prognostics and therapy.

Objective: The aim of this study was to determine whether intranasal administration of botulinum toxin type A (BTX-A) could relieve the typical symptoms of allergic rhinitis (AR) and alter substance P (SP)- and vasoactive intestinal peptide (VIP)-immunoreactive (IR) expression in nasal mucosa of AR animals sensitized with ovalbumin (OVA). Methods: AR was induced by intraperitoneal injection of OVA followed by its repeated intranasal instillation in female Wistar rats. Some AR animals were intranasally treated with a cotton strip containing BTX-A (10 U per nostril) for 1 h. After BTX-A treatment, OVA was repeatedly instilled in AR and AR + BTX-A groups every 2 days for 10 days. Subsequently, nasal symptoms were evaluated, and nasal secretions collected. Finally, the nasal mucosae of all animals were prepared for histological and immunohistochemical assessment. Results: BTX-A administration alleviated typical AR symptoms including rhinorrhea, nasal itching and sneezing, and subsequent intranasal repeated challenge with OVA did not trigger AR symptoms. After BTX-A treatment, inflammatory histological characteristics within the nasal mucosa of AR animals were absent, but atrophy of serous glands was observed. BTX-A decreased dense SP-IR and VIP-IR cells and fibers within and beneath the epithelium, around blood vessels and close to serous glands in AR animals. Conclusion: Local BTX-A treatment is an effective method to reduce AR symptoms. BTX-A decreased the excessive SP-IR and VIP-IR expression induced by OVA. Therefore, BTX-A may affect the nasal mucosa via the suppression of neuropeptides, playing a major role in autonomous mucosal innervation in the pathophysiology of AR.

Use of protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) has been associated with altered regional fat distribution, insulin resistance, and dyslipidemias. To assess how PI-based HAART affects adipocyte gene expression in male HIV-1-infected patients, reverse transcription-polymerase chain reaction was used to quantify messenger RNA expression of adipocyte transcription factors and adipocytokines in thigh and abdominal subcutaneous adipose tissue from male (1) HIV-1 seronegative subjects (control, n = 9), (2) asymptomatic treatment-naive HIV-1-infected patients (naive, n = 6), (3) HIV-1-infected patients who were receiving antiretroviral agents but never received PIs (PI naive, n = 5), (4) HIV-1-infected patients who were receiving PIbased HAART (PI, n = 7), and (5) HIV-1-infected patients who discontinued the PI component of their antiviral therapy more than 6 months before enrollment (past PI, n =7). In the PI group, the messenger RNA expression levels of the CCAAT/enhancer-binding protein α, leptin, and adiponectin (18%, P < .01; 23%, P < .05; and 13%, P < .05, respectively) were significantly lower than the levels measured in the PI-naive group. These results are consistent with previous studies on the effects of PIs on cultured adipocytes. Prospective longitudinal studies of thigh fat adipose tissue gene expression could provide further insights on the pathogenesis of metabolic complications associated with PI-based HAART.