KingMed-Pineal Joint Innovation Laboratory of Clinical Proteomics, Guangzhou KingMed Center for Clinical Laboratory Co., Ltd., Guangzhou, 510009, China; Beijing Pineal Diagnostics Co., Ltd., Beijing, 102206, China.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China.
Cancer Lett. 2023 Apr 28;560:216123. doi: 10.1016/j.canlet.2023.216123. Epub 2023 Mar 11.
Clinical next-generation sequencing (NGS) tests have enabled treatment recommendations for cancer patients with driver gene mutations. Targeted therapy options for patients without driver gene mutations are currently unavailable. Herein, we performed NGS and proteomics tests on 169 formalin-fixed paraffin-embedded (FFPE) samples of non-small cell lung cancers (NSCLC, 65), colorectal cancers (CRC, 61), thyroid carcinomas (THCA, 14), gastric cancers (GC, 2), gastrointestinal stromal tumors (GIST, 11), and malignant melanomas (MM, 6). Of the 169 samples, NGS detected 14 actionable mutated genes in 73 samples, providing treatment options for 43% of the patients. Proteomics identified 61 actionable clinical drug targets approved by the FDA or undergoing clinical trials in 122 samples, providing treatment options for 72% of the patients. In vivo experiments demonstrated that the Mitogen-Activated Protein Kinase (MEK) inhibitor could block lung tumor growth in mice with overexpression of Map2k1 protein. Therefore, protein overexpression is a potentially feasible indicator for guiding targeted therapies. Collectively, our analysis suggests that combining NGS and proteomics (genoproteomics) could expand the targeted treatment options to 85% of cancer patients.
临床下一代测序（NGS）检测使癌症患者的驱动基因突变治疗建议成为可能。目前，没有驱动基因突变的患者的靶向治疗选择是不存在的。在此，我们对 169 例福尔马林固定石蜡包埋（FFPE）的非小细胞肺癌（NSCLC，65 例）、结直肠癌（CRC，61 例）、甲状腺癌（THCA，14 例）、胃癌（GC，2 例）、胃肠道间质瘤（GIST，11 例）和恶性黑色素瘤（MM，6 例）进行了 NGS 和蛋白质组学检测。在 169 例样本中，NGS 在 73 例样本中检测到 14 个可操作的突变基因，为 43%的患者提供了治疗选择。蛋白质组学在 122 例样本中鉴定出 61 个经 FDA 批准或正在进行临床试验的可操作临床药物靶点，为 72%的患者提供了治疗选择。体内实验表明，丝裂原活化蛋白激酶（MEK）抑制剂可以阻断过度表达 Map2k1 蛋白的小鼠的肺肿瘤生长。因此，蛋白质过表达是指导靶向治疗的一个潜在可行指标。总的来说，我们的分析表明，将 NGS 和蛋白质组学（基因组蛋白质组学）相结合，可以将靶向治疗选择扩展到 85%的癌症患者。
