Comprehensive analysis of a novel subtype of immune microenvironment-derived HPV-infected colorectal cancer.

BACKGROUND: The current study proposed a novel subtype, Human papillomavirus (HPV)-infected colorectal cancer (CRC), to understand the impact of HPV on CRC. METHODS: We assessed the prevalence and clinical implications of HPV in CRC by integrating a single cohort in Guangdong Provincial People's Hospital and public datasets. Differential gene, pathway enrichment, and immune infiltration analysis were conducted to explore the patterns in HPV-infected CRC. Quantitative polymerase chain reaction, cell proliferation, scratch, and flow cytometry assays were employed to validate the impact of HPV on CRC. RESULTS: The study revealed a high prevalence of HPV infection in CRC, with infection rates ranging from 10% to 31%. There was also a significant increase in tumor proliferation in HPV-infected CRC. The study showed increased immune cell infiltration, including T cells, γδ T cells, cytotoxic cells, and plasmacytoid dendritic cells in HPV-infected CRC (P < 0.05). Furthermore, our findings confirmed that HPV infection promoted M1 polarization. Our results demonstrated that low ISM2 expression was associated with a less advanced clinical stage (P < 0.001) and better survival outcomes (P = 0.039). Low ISM2 expression correlated with a strong tumor immune response, potentially contributing to the improved survival observed in HPV-infected CRC. CONCLUSIONS: These findings provided a novel subtype of HPV-infected CRC. The subtype with a better prognosis showed a "hot" tumor immune microenvironment that may be responsive to immunotherapy.

The Labyrinthine Landscape of APP Processing: State of the Art and Possible Novel Soluble APP-Related Molecular Players in Traumatic Brain Injury and Neurodegeneration.

Amyloid Precursor Protein (APP) and its cleavage processes have been widely investigated in the past, in particular in the context of Alzheimer's Disease (AD). Evidence of an increased expression of APP and its amyloidogenic-related cleavage enzymes, ß-secretase 1 (BACE1) and γ-secretase, at the hit axon terminals following Traumatic Brain Injury (TBI), firstly suggested a correlation between TBI and AD. Indeed, mild and severe TBI have been recognised as influential risk factors for different neurodegenerative diseases, including AD. In the present work, we describe the state of the art of APP proteolytic processing, underlining the different roles of its cleavage fragments in both physiological and pathological contexts. Considering the neuroprotective role of the soluble APP alpha (sAPPα) fragment, we hypothesised that sAPPα could modulate the expression of genes of interest for AD and TBI. Hence, we present preliminary experiments addressing sAPPα-mediated regulation of BACE1, Isthmin 2 (ISM2), Tetraspanin-3 (TSPAN3) and the Vascular Endothelial Growth Factor (VEGFA), each discussed from a biological and pharmacological point of view in AD and TBI. We finally propose a neuroprotective interaction network, in which the Receptor for Activated C Kinase 1 (RACK1) and the signalling cascade of PKCßII/nELAV/VEGF play hub roles, suggesting that vasculogenic-targeting therapies could be a feasible approach for vascular-related brain injuries typical of AD and TBI.

Isthmin 2 is decreased in preeclampsia and highly expressed in choriocarcinoma.

INTRODUCTION: Isthmin 2 (ISM2) is a protein which expression in humans is almost specific to the placenta. There is no previous report in the literature that investigated this protein in preeclampsia or choriocarcinoma. METHODS: We conducted a prospective, cross-sectional study that included women with preeclampsia, gestational hypertension and normotensive pregnancy. We measured serum concentrations of ISM2 protein and performed immunohistochemistry in placenta tissues. We also performed immunohistochemistry of ISM2 in samples from choriocarcinoma and compare with lung, prostate, colon, gastric and breast cancers. RESULTS: A total of 81 patients were included, 30 with preeclampsia, 21 with gestational hypertension and 30 controls. The ISM2 protein was found to be decreased in patients with preeclampsia compared to the control group (P = 0.036). These results were confirmed by immunohistochemistry. We also found that ISM2 protein was overexpressed in choriocarcinoma. DISCUSSION: Taken together, our results suggest an angiogenic function for ISM2. Its serum level decreased in our patients with preeclampsia could be reflecting that it is involved in the pathogenesis of the disease; on the other hand its high expression in choriocarcinoma, indicates that ISM2 may play an active role in the angiogenesis of this and other cancers.