Frequent expression loss of Inter-alpha-trypsin inhibitor heavy chain (ITIH) genes in multiple human solid tumors: A systematic expression analysis

<p>Abstract</p> <p>Background</p> <p>The inter-alpha-trypsin inhibitors (ITI) are a family of plasma protease inhibitors, assembled from a light chain – bikunin, encoded by <it>AMBP </it>– and five homologous heavy chains (encoded by <it>ITIH1</it>, <it>ITIH2</it>, <it>ITIH3</it>, <it>ITIH4</it>, and <it>ITIH5</it>), contributing to extracellular matrix stability by covalent linkage to hyaluronan. So far, ITIH molecules have been shown to play a particularly important role in inflammation and carcinogenesis.</p> <p>Methods</p> <p>We systematically investigated differential gene expression of the <it>ITIH </it>gene family, as well as <it>AMBP </it>and the interacting partner <it>TNFAIP6 </it>in 13 different human tumor entities (of breast, endometrium, ovary, cervix, stomach, small intestine, colon, rectum, lung, thyroid, prostate, kidney, and pancreas) using cDNA dot blot analysis (Cancer Profiling Array, CPA), semiquantitative RT-PCR and immunohistochemistry.</p> <p>Results</p> <p>We found that <it>ITIH </it>genes are clearly downregulated in multiple human solid tumors, including breast, colon and lung cancer. Thus, <it>ITIH </it>genes may represent a family of putative tumor suppressor genes that should be analyzed in greater detail in the future. For an initial detailed analysis we chose <it>ITIH2 </it>expression in human breast cancer. Loss of <it>ITIH2 </it>expression in 70% of cases (n = 50, CPA) could be confirmed by real-time PCR in an additional set of breast cancers (n = 36). Next we studied ITIH2 expression on the protein level by analyzing a comprehensive tissue micro array including 185 invasive breast cancer specimens. We found a strong correlation (p < 0.001) between ITIH2 expression and estrogen receptor (ER) expression indicating that ER may be involved in the regulation of this ECM molecule.</p> <p>Conclusion</p> <p>Altogether, this is the first systematic analysis on the differential expression of <it>ITIH </it>genes in human cancer, showing frequent downregulation that may be associated with initiation and/or progression of these malignancies.</p

First Analysis of Human Coccidioides Isolates from New Mexico and the Southwest Four Corners Region: Implications for the Distributions of C. posadasii and C. immitis and Human Groups at Risk

Coccidioidomycosis (Valley Fever) is a disease caused by species of Coccidioides. The disease is endemic to arid regions of the Southwestern US and while most common in CA and AZ is also present in NM. We present the first genetic analysis of clinical isolates from NM. Travel and demographic information was available for a number of patients, which included individuals from NM and the Southwestern US Four Corners region. Multi-gene phylogenetic analyses revealed the presence of both C. posadasii and C. immitis. While NM is predicted to be within the endemic range for C. posadasii, our results expand the known range of C. immitis, often considered to be the &ldquo;California species&rdquo;. Five of eight infections for which patient ethnicity existed occurred in Native Americans, and two occurred in African Americans. Several isolates came from the northwestern part of NM&mdash;outside the predicted &ldquo;highly-endemic&rdquo; region. Our study suggests Native Americans represent an unrecognized at-risk group, and it provides a foundation for better defining the geographic distribution of the Coccidioides species and for preventing exposure among populations at risk. In the course of this study, we developed a reliable PCR-based method to distinguish species targeting regions of the mitochondrial genome

Comparison of Fungal and Bacterial Microbiomes of Bats and Their Cave Roosting Environments at El Malpais National Monument, New Mexico, USA

The arrival in North America of white-nose syndrome (WNS), a devastating fungal disease in bats, has emphasized the necessity of a comprehensive understanding of the bats’ external skin microbiota. Here, we investigated the composition of the natural bat microbiota pre-WNS and how they are acquired. The fur surfaces of 12 roosting bats, adjacent cave walls, and cave chamber air were sampled in two New Mexican lava caves. Bacterial and fungal diversity were assessed using Illumina MiSeq sequencing. Although many taxa were shared among the sample types, there were significant differences in alpha and beta diversity within and among communities. Bacterial phyla Actinobacteriota (39.1%) and Proteobacteria (27.9%) comprised two-thirds of the sequences. Fungal communities were dominated by Ascomycota (78.9%), followed by Basidiomycota (14.7%), and Mucoromycota (4.3%). Results for bacterial communities suggested that cave walls and cave air influence the bat microbiome and that the bat microbiome can have a reciprocal influence on the microbiome of cave walls. Fungal microbiomes of cave walls, air, and bats appear to have very low impact on each other. Our results begin to elucidate how cave environments may provide natural microbial defenses for bats, one facet in predicting the effect of WNS on western bats.</p