Graph Neural Networks (GNNs) have emerged as powerful tools for analyzing structured data, particularly in domains where relationships and interactions between entities are key. By leveraging the inherent graph structure in datasets, GNNs excel in capturing complex dependencies and patterns that traditional neural networks might miss. This advantage is especially pronounced in the field of computational biology, where the intricate connections between biological entities play a crucial role. In this context, Our work explores the application of GNNs to single-cell RNA sequencing (scRNA-seq) data, a domain characterized by complex and heterogeneous relationships. By extracting ligand-receptor (L-R) associations from LIANA and constructing Cell-Cell association networks with varying edge homophily ratios, based on L-R information, we enhance the biological relevance and accuracy of depicting cellular communication pathways. While standard GNN models like Graph Convolutional Networks (GCN), GraphSAGE, Graph Attention Networks (GAT), and MixHop often assume homophily (similar nodes are more likely to be connected), this assumption does not always hold in biological networks. To address this, we explore advanced graph neural network methods, such as Graph Convolutional Networks and Gated Bi-Kernel GNNs (GBK-GNN), that are specifically designed to handle heterophilic data. Our study spans across six diverse datasets, enabling a thorough comparison between heterophily-aware GNNs and traditional homophily-assuming models, including Multi-Layer Perceptrons, which disregards graph structure entirely. Our findings highlight the importance of considering data-specific characteristics in GNN applications, demonstrating that heterophily-focused methods can effectively decipher the complex patterns within scRNA-seq data. By integrating multi-omics data, including gene expression profiles and L-R interactions, we pave the way for more accurate and insightful analyses in computational biology, offering a more comprehensive understanding of cellular environments and interactions.