左侧结肠癌（LSCC）和右侧结肠癌（RSCC）表现出不同的生物学和临床特征。然而，它们在肿瘤发生和肿瘤微环境方面的差异仍不清楚。在本研究中，我们使用数据无关采集质谱（DIA-MS）从24名患者的新鲜肿瘤和邻近正常组织中对LSCC和RSCC的蛋白质组景观进行了分析。总共鉴定了7403个蛋白质组，其中7212个蛋白质组经过质量控制后用于进一步分析。通过比较LSCC和RSCC样本之间蛋白质组景观的差异，我们确定了2556个常见调控蛋白质组和1982个区域类型特异性调控蛋白质组。在LSCC和RSCC的发展过程中，代谢、生长、细胞分裂、细胞粘附和迁移通路被发现明显失调（P < 0.05），这在TCGA的转录组数据中得到了进一步确认。与RSCC相比，LSCC的免疫相关标志物大部分部分、免疫细胞浸润评分和整体免疫评分较高。本研究对LSCC和RSCC的肿瘤发生和免疫微环境特征进行了系统阐明，提高了我们对这两种癌症的认识水平。

Left-sided and right-sided colon cancer (LSCC and RSCC) display different biological and clinical characteristics. However, the differences in their tumorigenesis and tumor microenvironment remain unclear. In this study, we profiled the proteomic landscapes of LSCC and RSCC with data-independent acquisition mass spectrometry (DIA-MS) using fresh tumor and adjacent normal tissues from 24 patients. A total of 7403 proteingroups were primarily identified with DIA-MS. After quality control, 7212 proteingroups were used for further analysis. Through comparing the difference in proteomic profiles between LSCC and RSCC samples, 2556 commonly and 1982 region-type-specific regulated proteingroups were characterized. During the development of LSCC and RSCC, metabolic, growth, cell division, cell adhesion, and migration pathways were found to be significantly dysregulated (P < 0.05), which was further confirmed by transcriptome data from TCGA. Compared to RSCC, most parts of the immune-related signatures, immune cell infiltration scores, and overall immune scores of LSCC were higher. The systematic elucidation of proteomic and transcriptomic profiles in this work improves our understanding of tumorigenesis and immune microenvironment characteristics of LSCC and RSCC.