Molecular Characteristics, Cancer Immune of LRP1B and its relationship with Hedgehog Signalling Pathway in Colorectal Cancer

Wei Chong ^1* Yuan Liu ² Yang Zhong ² Yaodong Sang ¹ Xu Kang ¹ Xingyu Zhu ¹ Xiaoling Cui ¹ Xinyu Liu ¹ Xiaohan Wang ¹ Hao Chen ² Changqing Jing ¹ Leping Li ^1,2

• ¹ Shandong Provincial Hospital, Jinan, China
• ² Shandong University, Jinan, Shandong Province, China

Background: Colorectal cancer (CRC) is one of the malignant tumours in the digestive tract, which affects the health of people to a large extent. LDL receptor-related protein 1B (LRP1B) might serve as a crucial role in tumorigenesis and disease progression.We conducted a comparative analysis of differential gene expression, mutation patterns, drug sensitivity and cellular phenotypes among different subgroup of LRP1B expression level. Cellular and molecular experiments were further conducted to confirm the results of our analysis.Results: LRP1B was implicated as a tumortumour suppressor gene in our analysis. The results of experiments verified that the expression of LRP1B was decreased in CRC, and knocking down it was associated with poor prognosis. The molecular mechanism study revealed that LRP1B took negative acts on Hedgehog (Hh) signalingsignalling pathway to impact the cell cycle and apoptosis programs. Single cell analysis showed that T cells, B cells, epithelial cells and myeloid cells were significantly differentially infiltrated in high and low expression of LRP1B groups. Immune cell infiltration and drug sensitivities analysis demonstrated LRP1B played a markedly important role in immunotherapy or targeted therapy, implicating that restoring the function of LRP1B would be a prospective treatment target in CRC.Our results demonstrated that LRP1B may function as a tumortumour suppressor factor in CRC, which has significance in mutation, therapy and immune infiltration. Knockdown of LRP1B can activate the Hh pathway in tumor cells to inhibit several malignant biological behaviorsbehaviours.