Identification of a Proliferation Gene Cluster Associated with HPV E6/E7 Expression Level and Viral DNA Load in Invasive Cervical Carcinoma

Christophe Rosty; Michal Sheffer; Dafna Tsafrir; Nicolas Stransky; Ilan Tsafrir; Martine Peter; Patricia de Cremoux; Anne de La Rochefordiere; Remy Salmon; Thierry Dorval; Jean Paul Thiery; Jerome Couturier; Francois Radvanyi; Eytan Domany; Xavier Sastre-Garau

arXiv · q-bio/0511019

Identification of a Proliferation Gene Cluster Associated with HPV E6/E7 Expression Level and Viral DNA Load in Invasive Cervical Carcinoma

Christophe Rosty·Michal Sheffer·Dafna Tsafrir·Nicolas Stransky·Ilan Tsafrir·Martine Peter·Patricia de Cremoux·Anne de La Rochefordiere·Remy Salmon·Thierry Dorval·Jean Paul Thiery·Jerome Couturier·Francois Radvanyi·Eytan Domany·Xavier Sastre-Garau

View original source ↗Read source document ↗Export metadata ↓

Abstract

Specific HPV DNA sequences are associated with more than 90% of invasive carcinomas of the uterine cervix. Viral E6 and E7 oncogenes are key mediators in cell transformation by disrupting TP53 and RB pathways. To investigate molecular mechanisms involved in the progression of invasive cervical carcinoma, we performed a gene expression study on cases selected according to viral and clinical parameters. Using Coupled Two-Way Clustering and Sorting Points Into Neighbourhoods methods, we identified a Cervical Cancer Proliferation Cluster composed of 163 highly correlated transcripts, many of which corresponded to E2F pathway genes controlling cell proliferation, whereas no primary TP53 targets were present in this cluster. The average expression level of the genes of this cluster was higher in tumours with an early relapse than in tumours with a favourable course (P=0.026). Moreover, we found that E6/E7 mRNA expression level was positively correlated with the expression level of the cluster genes and with viral DNA load. These findings suggest that HPV E6/E7 expression level plays a key role in the progression of invasive carcinoma of the uterine cervix via the deregulation of cellular genes controlling tumour cell proliferation. HPV expression level may thus correspond to a biological marker useful for prognosis assessment and specific therapy of the disease.

Explore related subjects

q-bio.TO q-bio.QM

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Christophe Rosty, Michal Sheffer, Dafna Tsafrir, Nicolas Stransky, Ilan Tsafrir, Martine Peter, Patricia de Cremoux, Anne de La Rochefordiere, Remy Salmon, Thierry Dorval, Jean Paul Thiery, Jerome Couturier, Francois Radvanyi, Eytan Domany, Xavier Sastre-Garau. 2005-11-15. Identification of a Proliferation Gene Cluster Associated with HPV E6/E7 Expression Level and Viral DNA Load in Invasive Cervical Carcinoma. https://arxiv.org/abs/q-bio/0511019

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Simulation and Analysis of Solute Transport in Multi-Lymphangion Lymphatic Vessels

The lymphatic system (LS), a body-wide network of vessels and lymphoid organs governing fluid homeostasis and immune surveillance, has so far not been investigated as a domain for diagnostic and therapeutic molecular communications (MC) applications, despite several properties that make it a promising, complementary alternative to the cardiovascular system. These favorable properties include slower flow, simpler and less dense molecular fluid composition, and direct anatomical access to lymph nodes. Realizing this potential, however, requires a quantitative understanding of how solutes propagate through the LS, a problem that, unlike lymph flow itself, remains largely unaddressed in the literature. As a first step towards narrowing this gap, we develop a particle-based simulation (PBS) framework of solute transport through a three-dimensional chain of valve-separated, concatenated vessel segments, called lymphangions. We simulate the spatiotemporal evolution of solute concentration and qualitatively validate the resulting transport dynamics against existing in vivo measurements of fluorescent tracer propagation in multi-lymphangion lymphatic vessels. Our simulations show that the valve-gated nature of solute transport in lymphatic vessels leads to bursty solute concentrations over time, a characteristic that can also be observed in vivo. Additionally, we find that, within one pumping period, peak timing is dictated by the valves' synchronizing effect rather than the particle release time, while diffusivity and receiver placement determine peak sharpness. Overall, the proposed PBS framework provides a first quantitative basis for solute transport modeling in the LS and several concrete application scenarios for MC in this underexplored domain. Supplementary video material illustrating the PBS is publicly available on Zenodo [DOI: 10.5281/zenodo.21888066].

q-bio.TO↗

arXiv2026

A Combined ODE Model of Carbohydrate Fermentation and Colorectal Cancer

We formulate and analyze a system of non-linear ordinary differential equations that describe key metabolic and immunological interactions between butyrate produced by fiber-fermenting gut microbiota, colorectal cancer cells and host cell populations. The model is studied both independently and in conjunction with a pre-existing carbohydrate fermentation model. The parameter space is explored through sensitivity analyses. Simulation experiments are conducted to illustrate the emergence of varying dynamical behaviour driven by butyrate availability. Our model predicts that butyrate production is driven by fiber consumption and further supported by probiotics in the case of microbial dysbiosis. It also suggests that butyrate may help in suppressing tumour growth. We also show that by adding noise with sufficiently high intensity, cancer elimination occurs almost surely in infinite time and that this threshold level of noise intensity decreases with increasing butyrate concentrations.

q-bio.TO↗

arXiv2026

Intestinal villi and crypt density robustly maximizes nutrient absorption

The villi and crypts of the gastrointestinal tract increase the effective surface area of the intestinal mucosa, potentially enhancing nutrient absorption. It is commonly assumed that this is their primary function, and that a higher villi density necessarily leads to improved absorption. However, when villi are packed too closely together, diffusion can be hindered, potentially offsetting this benefit. In this work, we investigate quantitatively the relationship between the density of these structures and the overall efficiency of absorption. In three different simplified geometries, approximating leaf-like villi, finger-like villi, and colonic crypts, we calculate analytically the concentration profile and the absorption flux, assuming that there is only diffusion between these structures while the lumen is well mixed. When plotting the absorption flux per unit of gut length as a function of the structures' density, we observe that there is a density maximizing absorption. We study numerically this optimum. We find that it is robust to the nutrient absorption properties: a geometry optimal for one nutrient is close to optimum for another nutrient. Physiological data from various animal species fall within this predicted optimal range, consistent with the hypothesis that structure density is shaped by selection for efficient nutrient uptake.

q-bio.TO↗