Biology subjects

Rahrmann, E.

Publications and source records attributed to Rahrmann, E..

3 recordsLinked to original sources

bioRxiv2025

Optimizing miRNA-Based Breast Cancer Subtyping with AHALA: A Multi-Stage Classification Approach

This paper presents the Adaptive Hill Climbing Artificial Lemming Algorithm (AHALA), a novel optimization method designed to improve miRNA-based breast cancer subtyping and classification. By integrating Hill Climbing into the Artificial Lemming Algorithm, AHALA balances global exploration and local exploitation through adaptive boundary handling and dynamic step-size decay. Applied to breast cancer miRNA expression data, AHALA excelled in multi-classification tasks, achieving an accuracy of 95.74%, precision of 95.98%, recall of 95.74%, F1 score of 95.74%, and AUC of 0.9682. These results highlight its ability to distinguish between breast cancer subtypes, including Luminal A, Luminal B, HER2-enriched, and Basal-like. Feature selection powered by AHALA identified key miRNAs--hsa-miR-190b, hsa-miR-429, hsa-miR-505-3p, hsa-miR-3614-5p, and hsa-miR-935--linked to subtype differentiation. Additionally, AHALA optimized neural network hyperparameters, including hidden layer size, learning rate, and batch size, enhancing classification performance. These findings demonstrate AHALAs potential as a robust tool for miRNA classification, biomarker discovery, and machine learning optimization in breast cancer research, contributing to improved diagnostics and treatment strategies.

cancer biology↗

bioRxiv2020

KCNQ gene family members act as both tumor suppressors and oncogenes in gastrointestinal cancers

Voltage sensitive potassium channels play an important role in controlling membrane potential and ionic homeostasis in the gut and have been implicated in gastrointestinal (GI) cancers. Through large scale analysis of 1594 patients with GI cancers coupled with in vitro models we find KCNQ family genes are mutated in ~30% of patients, and play therapeutically targetable roles in GI cancer growth. KCNQ1 and KCNQ3 mediate the WNT pathway and MYC to increase proliferation, and its resultant effects on cadherins junctions. This also highlights novel roles for KCNQ3 in non-excitable tissues. We additionally discover that activity of KCNQ3 sensitises cancer cells to existing potassium channel inhibitors, and that inhibition of KCNQ activity reduces proliferation of GI cancer. These findings reveal a novel and exploitable role for potassium channels in the advancement of human cancer, and highlight that supplemental treatments for GI cancers may exist through KCNQ inhibitors. SIGNIFICANCEKCNQ channels modulate the WNT pathway and MYC signalling, and drive growth of gastrointestinal cancers. Available drugs modulate these pathways and offer therapeutic potential in gastrointestinal cancer.

cancer biology↗

bioRxiv2019

SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis

Semaphorins, specifically type IV, are important regulators of axonal guidance and have been increasingly implicated in poor prognoses in a number of different solid cancers. In conjunction with their cognate PLXNB family receptors, type IV members have been increasingly shown to mediate oncogenic functions necessary for tumor development and malignant spread. In this study, we investigated the role of semaphorin 4C (SEMA4C) in osteosarcoma growth, progression, and metastasis. We investigated the expression and localization of SEMA4C in primary osteosarcoma patient tissues and its tumorigenic functions in these malignancies. We demonstrate that overexpression of SEMA4C promotes properties of cellular transformation, while RNAi knockdown of SEMA4C promotes adhesion and reduces cellular proliferation, colony formation, migration, wound healing, tumor growth, and lung metastasis. These phenotypic changes were accompanied by reductions in activated AKT signaling, G1 cell cycle delay, and decreases in expression of mesenchymal marker genes SNAI1, SNAI2, and TWIST1. Lastly, monoclonal antibody blockade of SEMA4C in vitro mirrored that of the genetic studies. Together, our results indicate a multi-dimensional oncogenic role for SEMA4C in metastatic osteosarcoma and more importantly that SEMA4C has actionable clinical potential.

cancer biology↗