Project description:RNA was extracted from 57 LUAD patients hospitalized from 2004 to 2010 at the Pasteur Hospital (Departments of Pulmonary Medicine, and Thoracic Surgery, CHU de Nice, France) and 11 normal lung tissue specimens taken from areas at standard distance (3 cm) from the same cohort of patients.The diagnosis of LUAD patients was based on examination of all tumor specimens using the 7th pTNM classification and on the last histological classification of NSCLC. Written informed consent was obtained from participants after explaining the nature of the study, which was approved by the research ethics board of the Nice University hospital and was performed according to the guidelines of the Declaration of Helsinki. The main clinical and pathological data are summarized. Enrollment of patients in our study was conditioned by stringent criteria such as obtained signed consent, availability of resected surgical specimens, good quality RNA and time of follow-up for surviving patients (min 40 months for surviving patients).
Project description:Lung adenocarcinoma (LUAD) is the main histologic subtype of lung cancer, and its incidence is on the rise. However, since the vast majority of patients are already in advanced stages at the time of diagnosis, their 5-year survival rate is only 15%, so it is urgent to explore the mechanism of the development of LUAD and improve the survival time of patients. Interleukin-11 (IL-11), a member of the IL-6 cytokine family, has an influential role in the development and progression of a variety of tumors, but the specific molecular mechanisms that promote the malignant progression of LUAD are unknown. Here, we found that the IL-11-induced activation of Akt, Erk, and STAT3 could be inhibited by knocking out the expression of Gαi1/3. In contrast, overexpression of Gαi1/3 could enhance IL-11-induced signaling. The binding of Gαi1/3 to GP130 mediates IL-11-induced downstream activation of Akt-mTOR, Erk, and STAT3, which requires recruitment of Grb2-associated binding protein 1 (Gab1). In LUAD cells, shGαi1/3 inhibited cell growth, proliferation, and migration as well as blocked the tumor-promoting ability of IL-11. However, overexpression of Gαi1/3 enhanced the IL-11-induced cell growth, proliferation, and migration. ShGαi1/3 also inhibited the proliferation of LUAD cells in vivo. Overall, the findings of this study demonstrate the Gαi1 and Gαi3 are critical for IL-11 signal transduction. Moreover, we reveal that Gαi1 and Gαi3 are highly expressed and associated with poor overall survival in lung adenocarcinoma and may thus act as potential therapeutic targets in LUAD. These results provide a novel therapeutic strategy for LUAD patients with upregulated IL-11 expression.
Project description:We report the application of Hi-C technology for high-throughput profiling of LUAD and normal tissues. By obtaining over three billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of LUAD. We found the main conversion type of compartment is A→B in tumor tissues, 216 tumor-specific TADs and 41 distinct enhancer-promoter loops in tumor tissue. And these chromatin structure variations are mainly on chromosome 3. We also found 5 most important genes (SYT16, NCEH1, NXPE3, MB21D2, and DZIP1L), which were detected in both A→B compartment, TADs and chromatin loops.
Project description:Glioblastoma multiforme (GBM) is the most common and deadliest primary brain tumor. Its prognosis is inexorably unfavorable, as these tumors drive affected patients to death usually within 15 months after diagnosis (short term survivors, ST), with the only exception of a small fraction of patients (long term survivors, LT) surviving longer than 36 months. Even after the frontline therapeutic approach, including surgical resection followed by chemo- and radiotherapy, the cause of death in most cases is tumor recurrence, which occurs in peritumoral tissues in about 95% of patients. Here, we provide a comprehensive molecular analysis of a set of ST and LT samples derived from frankly tumoral areas (C) and from the peritumoral regions (P) of the same patients. By performing microRNA deep sequencing, we collected data showing that P areas differ from healthy white matter, but share with C samples, a number of microRNAs
Project description:Laryngeal squamous cell carcinoma (LSCC) is a common form of head and neck cancer with poor prognosis. However, the mechanism underlying the pathogenesis of LSCC remains unclear. We performed high throughout sequencing to identify miRNA that associated with LSCC progression.Small RNA libraries were constructed followed by sequencing on a cohort of LSCC tissues (57 samples) and paired adjacent normal mucosa tissues (57 samples).
Project description:Laryngeal squamous cell carcinoma (LSCC) is a common form of head and neck cancer with poor prognosis. However, the mechanism underlying the pathogenesis of LSCC remains unclear. We performed high throughout transcriptome sequencing to identify lncRNA and mRNA that associated with LSCC progression.Transcriptome sequencing were performed on a cohort of LSCC tissues (57 samples) and paired adjacent normal mucosa tissues (57 samples).
Project description:Purified NK cells from human intratumoral and peritumoral tissues tissues were first enriched by MACS using NK Cell Isolation Kit (Miltenyi Biotec, German) and CD96+/- hepatic NK cells were isolated by FACS Aria cell sorter (BD Biosciences, United States) to attain a purity greater than 95%.
Project description:Genome wide DNA methylation profiling of peripheral blood mononuclear cells(PBMCs) in normal and LUAD samples. The Illumina Infinium 850k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 820,000 CpGs in PBMC samples. Samples included 35 LUAD patients and 50 normal controls.