Combining low-dose CT-based radiomics and metabolomics for early lung cancer screening support

Due to its predominantly asymptomatic or mildly symptomatic progression, lung cancer is often diagnosed in advanced stages, resulting in poorer survival rates for patients. As with other cancers, early detection significantly improves the chances of successful treatment. Early diagnosis can be facilitated through screening programs designed to detect lung tissue tumors when they are still small, typically around 3mm in size. However, the analysis of extensive screening program data is hampered by limited access to medical experts. In this study, we developed a procedure for identifying potential malignant neoplastic lesions within lung parenchyma. The system leverages machine learning (ML) techniques applied to two types of measurements: low-dose Computed Tomography-based radiomics and metabolomics. Using data from two Polish screening programs, two ML algorithms were tested, along with various integration methods, to create a final model that combines both modalities to support lung cancer screening

Differential expression of HSPA1 and HSPA2 proteins in human tissues; tissue microarray-based immunohistochemical study

In the present study we determined the expression pattern of HSPA1 and HSPA2 proteins in various normal human tissues by tissue-microarray based immunohistochemical analysis. Both proteins belong to the HSPA (HSP70) family of heat shock proteins. The HSPA2 is encoded by the gene originally defined as testis-specific, while HSPA1 is encoded by the stress-inducible genes (HSPA1A and HSPA1B). Our study revealed that both proteins are expressed only in some tissues from the 24 ones examined. HSPA2 was detected in adrenal gland, bronchus, cerebellum, cerebrum, colon, esophagus, kidney, skin, small intestine, stomach and testis, but not in adipose tissue, bladder, breast, cardiac muscle, diaphragm, liver, lung, lymph node, pancreas, prostate, skeletal muscle, spleen, thyroid. Expression of HSPA1 was detected in adrenal gland, bladder, breast, bronchus, cardiac muscle, esophagus, kidney, prostate, skin, but not in other tissues examined. Moreover, HSPA2 and HSPA1 proteins were found to be expressed in a cell-type-specific manner. The most pronounced cell-type expression pattern was found for HSPA2 protein. In the case of stratified squamous epithelia of the skin and esophagus, as well as in ciliated pseudostratified columnar epithelium lining respiratory tract, the HSPA2 positive cells were located in the basal layer. In the colon, small intestine and bronchus epithelia HSPA2 was detected in goblet cells. In adrenal gland cortex HSPA2 expression was limited to cells of zona reticularis. The presented results clearly show that certain human tissues constitutively express varying levels of HSPA1 and HSPA2 proteins in a highly differentiated way. Thus, our study can help designing experimental models suitable for cell- and tissue-type-specific functional differences between HSPA2 and HSPA1 proteins in human tissues

Les occupations de l'âge du Bronze du site des Feuilly à Saint-Priest (Rhône) : présentation liminaire

International audienc

Partial-Body Irradiation in Patients with Prostate Cancer Treated with IMRT Has Little Effect on the Composition of Serum Proteome

Partial body irradiation during cancer radiotherapy (RT) induces a response of irradiated tissues that could be observed at the level of serum proteome. Here we aimed to characterize the response to RT in group of patients treated because of prostate cancer. Five consecutive blood samples were collected before, during, and after the end of RT in a group of 126 patients who received definitive treatment with a maximum dose of 76 Gy. Serum peptidome, which was profiled in the 2000–16,000 Da range using MALDI-MS. Serum proteins were identified and quantified using the shotgun LC-MS/MS approach. The majority of changes in serum peptidome were detected between pre-treatment samples and samples collected after 3–4 weeks of RT (~25% of registered peptides changed their abundances significantly), yet the intensity of observed changes was not correlated significantly with the degree of acute radiation toxicity or the volume of irradiated tissues. Furthermore, there were a few serum proteins identified, the abundances of which were different in pre-RT and post-RT samples, including immunity and inflammation-related factors. Observed effects were apparently weaker than in comparable groups of head and neck cancer patients in spite of similar radiation doses and volumes of irradiated tissues in both groups. We concluded that changes observed at the level of serum proteome were low for this cohort of prostate cancer patients, although the specific components involved are associated with immunity and inflammation, and reflect the characteristic acute response of the human body to radiation

Sépultures de l’Antiquité tardive en Limagne, Puy-de-Dôme, Auvergne : les sites de La Grande Borne à Clermont-Ferrand et de Montussang à Aigueperse

International audienc

BRAFV600E-Associated Gene Expression Profile: Early Changes in the Transcriptome, Based on a Transgenic Mouse Model of Papillary Thyroid Carcinoma

<div><p>Background</p><p>The molecular mechanisms driving the papillary thyroid carcinoma (PTC) are still poorly understood. The most frequent genetic alteration in PTC is the <i>BRAF</i>V600E mutation–its impact may extend even beyond PTC genomic profile and influence the tumor characteristics and even clinical behavior.</p><p>Methods</p><p>In order to identify <i>BRAF</i>-dependent signature of early carcinogenesis in PTC, a transgenic mouse model with <i>BRAF</i>V600E-induced PTC was developed. Mice thyroid samples were used in microarray analysis and the data were referred to a human thyroid dataset.</p><p>Results</p><p>Most of <i>BRAF</i>(+) mice developed malignant lesions. Nevertheless, 16% of <i>BRAF</i>(+) mice displayed only benign hyperplastic lesions or apparently asymptomatic thyroids. After comparison of non-malignant <i>BRAF</i>(+) thyroids to <i>BRAF</i>(−) ones, we selected 862 significantly deregulated genes. When the mouse <i>BRAF</i>-dependent signature was transposed to the human HG-U133A microarray, we identified 532 genes, potentially indicating the <i>BRAF</i> signature (representing early changes, not related to developed malignant tumor). Comparing <i>BRAF</i>(+) PTCs to healthy human thyroids, PTCs without <i>BRAF</i> and <i>RET</i> alterations and <i>RET</i>(+), <i>RAS</i>(+) PTCs, 18 of these 532 genes displayed significantly deregulated expression in all subgroups. All 18 genes, among them 7 novel and previously not reported, were validated as <i>BRAF</i>V600E-specific in the dataset of independent PTC samples, made available by The Cancer Genome Atlas Project.</p><p>Conclusion</p><p>The study identified 7 <i>BRAF</i>-induced genes that are specific for <i>BRAF V600E</i>-driven PTC and not previously reported as related to <i>BRAF</i> mutation or thyroid carcinoma: <i>MMD</i>, <i>ITPR3</i>, <i>AACS</i>, <i>LAD1</i>, <i>PVRL3</i>, <i>ALDH3B1</i>, and <i>RASA1</i>. The full signature of <i>BRAF</i>-related 532 genes may encompass other <i>BRAF</i>-related important transcripts and require further study.</p></div

Boxplots of 18 genes chosen for validation.

<p>Expression distribution for each gene from our microarray data (on the left), The Cancer Genome Atlas Project data (on the right). The expression levels of analyzed genes are presented in <i>BRAF</i>(+) PTCs, <i>RET</i>(+), <i>RAS</i>(+), PTC(-) and healthy thyroids (HT) from left to right, respectively (as presented at the bottom of the figure). FDR values are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143688#pone.0143688.t004" target="_blank">Table 4</a>.</p

Hierarchical clustering of mouse samples.

<p>Thirty-eight mouse samples based on 1020 probe sets significantly differentiating between <i>BRAF</i>(+) and <i>BRAF</i>(−) non-malignant mouse samples (marked with blue and cyan respectively). PTCs (red); borderline thyroid lesions (BL; magenta); benign hyperplastic thyroid lesions (BHL; dark green); asymptomatic thyroid glands (AT; green).</p