Department of General Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.
Department of Gastrointestinal Surgery, The Second Hospital of Shandong University, Shandong 250000, P.R. China.
Int J Oncol. 2019 Aug;55(2):439-450. doi: 10.3892/ijo.2019.4833. Epub 2019 Jun 27.
Colorectal cancer (CRC) is one of the most common malignancies worldwide. At present, CRC can often be treated upon diagnosis at stage I or II, or when dysplasia is detected; however, 60‑70% of cases are not diagnosed until they have developed into late stages of the disease or until the malignancy is identified. Diagnosis of CRC at an early stage remains a challenge due to the absence of early‑stage‑specific biomarkers. To identify potential targets of early stage CRC, label‑free proteomics analysis was applied to paired tumor‑benign tissue samples from patients with stage II CRC (n=21). A total of 2,968 proteins were identified; corresponding RNA‑Sequencing data were retrieved from The Cancer Genome Atlas‑colon adenocarcinoma. Numerous bioinformatics methods, including differential expression analysis, weighted correlation network analysis, Gene Ontology and protein‑protein interaction analyses, were applied to the proteomics and transcriptomics data. A total of 111 key proteins, which appeared as both differentially expressed proteins and mRNAs in the hub module, were identified as key candidates. Among these, three potential targets [protein‑arginine deiminase type‑2 (PADI2), Fc fragment of IgG binding protein (FCGBP) and phosphoserine aminotransferase 1] were identified from the pathological data. Furthermore, the survival analysis indicated that PADI2 and FCGBP were associated with the prognosis of CRC. The findings of the present study suggested potential targets for the identification of early stage CRC, and may improve understanding of the mechanism underlying the occurrence of CRC.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一。目前，CRC 通常可以在 I 期或 II 期诊断时，或在发现异型增生时进行治疗；然而，60-70%的病例在发展为晚期疾病或恶性肿瘤被识别之前无法诊断。由于缺乏早期特异性生物标志物，CRC 的早期诊断仍然是一个挑战。为了确定早期 CRC 的潜在靶点，应用无标记蛋白质组学分析对来自 II 期 CRC 患者的配对肿瘤-良性组织样本（n=21）进行了分析。共鉴定出 2968 种蛋白质；从癌症基因组图谱-结肠腺癌中检索到相应的 RNA-测序数据。应用了许多生物信息学方法，包括差异表达分析、加权相关网络分析、GO 分析和蛋白质-蛋白质相互作用分析，对蛋白质组学和转录组学数据进行了分析。总共鉴定出 111 个关键蛋白，这些蛋白在枢纽模块中既表现为差异表达蛋白，又表现为差异表达 mRNA，被认为是关键候选物。其中，从病理数据中鉴定出了 3 个潜在靶点[蛋白精氨酸脱亚氨酶 2（PADI2）、免疫球蛋白 G 结合蛋白 Fc 片段（FCGBP）和磷酸丝氨酸氨基转移酶 1]。此外，生存分析表明 PADI2 和 FCGBP 与 CRC 的预后相关。本研究的结果表明了识别早期 CRC 的潜在靶点，并可能有助于深入了解 CRC 发生的机制。
