LRP1B, short for low-density lipoprotein receptor-related protein 1B, is a giant member of the LDLR protein family. Members of this family have diverse biological functions, from cargo transport to cell signaling. LRP1B is often considered a putative tumor suppressor, and its inactivation by genetic and epigenetic mechanisms is frequently observed in human cancer [1].

LRP1B mutations have been associated with various cancer-related phenotypes. In lung adenocarcinoma, LRP1B mutation is a potential biomarker for immunotherapy. It is related to increased tumor-infiltrating lymphocytes, higher tumor mutation burden, and prolonged progression-free survival, and it affects the sensitivity of cells to ferroptosis by modulating SLC7A11 expression through STAT3 phosphorylation [3,6]. In tubo-ovarian high-grade serous carcinoma, high cytoplasmic LRP1B expression in tumor and stroma cells is significantly associated with prolonged overall and progression-free survival, making it a significant prognostic marker [4]. In liver hepatocellular carcinoma, LRP1B mutation is related to high tumor mutation burden and poor prognosis [5]. In gastric cancer, LRP1B gene mutation is an independent risk factor for disease-free survival, and LRP1B-positive tumor cells are associated with higher levels of certain immune cells and represent an independent protective factor for disease-free survival [2,7].

In conclusion, LRP1B is a crucial gene with significant implications in cancer. Its inactivation or mutation is linked to various cancer-related outcomes, such as prognosis and response to immunotherapy. Research on LRP1B, especially through studies of its mutation status in different cancers, helps in understanding cancer biology and may provide new directions for cancer treatment and prognosis prediction.

References:

1. Príncipe, Catarina, Dionísio de Sousa, Isabel J, Prazeres, Hugo, Soares, Paula, Lima, Raquel T. 2021. LRP1B: A Giant Lost in Cancer Translation. In Pharmaceuticals (Basel, Switzerland), 14, . doi:10.3390/ph14090836. https://pubmed.ncbi.nlm.nih.gov/34577535/

2. López, María J, Carbajal, Junior, Alfaro, Alejandro L, Pinto, Joseph A, Fajardo, Williams. 2022. Characteristics of gastric cancer around the world. In Critical reviews in oncology/hematology, 181, 103841. doi:10.1016/j.critrevonc.2022.103841. https://pubmed.ncbi.nlm.nih.gov/36240980/

3. Ke, Zi-Hao, Chen, Ying, Yu, Tao, Xiang, Yan, Lu, Kai-Hua. . LRP1B Suppresses Immunotherapy Efficacy in Lung Adenocarcinoma by Preventing Ferroptosis. In Cancer medicine, 13, e70486. doi:10.1002/cam4.70486. https://pubmed.ncbi.nlm.nih.gov/39660409/

4. Kolb, Svenja, Hoffmann, Inga, Monjé, Nanna, Sinn, Bruno V, Taube, Eliane T. 2023. LRP1B-a prognostic marker in tubo-ovarian high-grade serous carcinoma. In Human pathology, 141, 158-168. doi:10.1016/j.humpath.2023.09.001. https://pubmed.ncbi.nlm.nih.gov/37742945/

5. Yu, Ge, Mu, Han, Fang, Feng, Xiong, Qingqing, Cui, Yunlong. 2022. LRP1B mutation associates with increased tumor mutation burden and inferior prognosis in liver hepatocellular carcinoma. In Medicine, 101, e29763. doi:10.1097/MD.0000000000029763. https://pubmed.ncbi.nlm.nih.gov/35777027/

6. He, Ziyi, Feng, Wei, Wang, Yuxuan, Shen, Shiyu, Huang, Haitao. 2023. LRP1B mutation is associated with tumor immune microenvironment and progression-free survival in lung adenocarcinoma treated with immune checkpoint inhibitors. In Translational lung cancer research, 12, 510-529. doi:10.21037/tlcr-23-39. https://pubmed.ncbi.nlm.nih.gov/37057124/

7. Wang, Rui, Zhang, Guangtao, Zhu, Xiaohong, Ma, Fangqi, Zhao, Aiguang. 2023. Prognostic Implications of LRP1B and Its Relationship with the Tumor-Infiltrating Immune Cells in Gastric Cancer. In Cancers, 15, . doi:10.3390/cancers15245759. https://pubmed.ncbi.nlm.nih.gov/38136305/