Cheng Lin, Weng Bangbi, Jia Changsheng, Zhang Lin, Hu Bin, Deng Li, Mou Nan, Sun Fengjun, Hu Jing
Department of Pharmacy, The First Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing, China.
Front Pharmacol. 2022 Aug 19;13:977025. doi: 10.3389/fphar.2022.977025. eCollection 2022.
The efferocytosis-related molecules have been considered to be correlated with the resistance to cancer chemotherapy. The aim of this study was to investigate the expression and significance of efferocytosis-related molecules in cancers and the correlation of their expression with anticancer drug sensitivity, and provide new potential targets and treatment options for cancers. We investigated the differential expression of 15 efferocytosis-related molecules (Axl, Tyro3, MerTK, CX3CL1, Tim-4, BAI1, Stab2, Gas6, IDO1, Rac1, MFGE8, ICAM-1, CD47, CD31, and PD-L1) and other 12 common immune checkpoint-related molecules in tumor and normal tissues, the correlation between their expression and various clinicopathological features in 16 types of cancers using publicly available pancancer datasets in The Cancer Genome Atlas. We also analyzed the correlation of the expression of efferocytosis and immune checkpoint related molecules with 126 types of anticancer drugs sensitivity using drug-RNA-seq data. There is a panel of circulating molecules among the 27 molecules. Based on the results of differential expression and correlation with various clinicopathological features of efferocytosis-related molecules in cancers, we identified new potential therapeutic targets for anticancer therapy, such as Axl for kidney renal clear cell carcinoma, Tyro3 for liver hepatocellular carcinoma, and IDO1 for renal papillary cell carcinoma. Except for BAI1, CD31, and MerTK, the enhanced expressions of Axl, Tyro3, Gas6, MFGE8, Stab2, Tim-4, CX3CL1, IDO1, Rac1, and PD-L1 were associated with decreased sensitivity of the cancer cells to many anti-cancer drugs; however, for other common immune checkpoint-related molecules, only enhanced expressions of PD-1, CD28, CTLA4, and HVEM were associated with decreased sensitivity of the cancer cells to a few drugs. The efferocytosis-related molecules were significantly associated with clinical outcomes in many types of cancers and played important roles in resistance to chemotherapy. Combination therapy targeting efferocytosis-related molecules and other immune checkpoint-related molecules is necessary to reduce resistance to chemotherapy.
胞葬作用相关分子被认为与癌症化疗耐药性相关。本研究旨在探讨胞葬作用相关分子在癌症中的表达及意义，以及其表达与抗癌药物敏感性的相关性，为癌症提供新的潜在靶点和治疗方案。我们利用癌症基因组图谱中公开的泛癌数据集，研究了15种胞葬作用相关分子（Axl、Tyro3、MerTK、CX3CL1、Tim-4、BAI1、Stab2、Gas6、IDO1、Rac1、MFGE8、ICAM-1、CD47、CD31和PD-L1）以及其他12种常见免疫检查点相关分子在肿瘤组织和正常组织中的差异表达，及其表达与16种癌症中各种临床病理特征的相关性。我们还利用药物-RNA测序数据，分析了胞葬作用和免疫检查点相关分子的表达与126种抗癌药物敏感性的相关性。在这27种分子中有一组循环分子。基于癌症中胞葬作用相关分子的差异表达结果及其与各种临床病理特征的相关性，我们确定了抗癌治疗的新潜在靶点，如肾透明细胞癌的Axl、肝细胞癌的Tyro3和肾乳头状细胞癌的IDO1。除BAI1、CD31和MerTK外，Axl、Tyro3、Gas6、MFGE8、Stab2、Tim-4、CX3CL1、IDO1、Rac1和PD-L1的表达增强与癌细胞对多种抗癌药物的敏感性降低相关；然而对于其他常见免疫检查点相关分子，只有PD-1、CD28、CTLA4和HVEM的表达增强与癌细胞对少数药物的敏感性降低相关。胞葬作用相关分子在多种癌症的临床结局中显著相关，在化疗耐药中起重要作用。靶向胞葬作用相关分子和其他免疫检查点相关分子的联合治疗对于降低化疗耐药性是必要的。
