Li Shu, Qu Jialing, Wang Xiaotong, Zou Qin, Li Chunli
Department of Clinical Laboratory, Women and Children's Hospital of Chongqing Medical University, Chongqing 401174, P.R. China.
Department of Clinical Laboratory, Chongqing Health Center for Women and Children, Chongqing 401174, P.R. China.
Oncol Lett. 2023 Jul 27;26(3):393. doi: 10.3892/ol.2023.13979. eCollection 2023 Sep.
Src homology-2 domain-containing protein tyrosine phosphatase (SHP2), encoded by protein tyrosine phosphatase non-receptor type 11 (PTPN11), is widely expressed in several human tissue types, and plays an important role in a variety of diseases. The present study assessed the impact of SHP2 on the occurrence, development and prognosis of solid tumors. The transcriptome sequencing data of 33 cancer types were downloaded from The Cancer Genome Atlas database. Clinical information of the corresponding patients, tumor mutational burden and information pertinent to microsatellite instability were also downloaded. The log-rank test and univariate Cox's regression test were used to evaluate patient survival. The 'ESTIMATE' method was used to assess the tumor microenvironment, and the 'CIBERSORT' algorithm was used to evaluate tumor immune cell infiltration. Spearman's correlation analysis was used to evaluate the correlation between SHP2 expression and the targets identified. ELISA was used to assess the SHP2 expression levels in peripheral blood samples of patients with breast, ovarian, endometrial and cervical cancer. The data indicated that the expression levels of SHP2 were increased in a variety of tumor tissues, and were associated with tumor progression and prognosis. In peripheral blood, the positive rates of SHP2 expression in breast cancer (71.43%) and ovarian cancer (58.82%) were significantly higher than those in the corresponding control groups. However, the positive rates of SHP2 expression in patients with endometrial cancer (31.03%) and cervical cancer (41.30%) were significantly lower than those in the corresponding control groups. Increased SHP2 expression improved overall survival (OS) and disease free survival (DFS) time in patients with kidney renal clear cell carcinoma. However, increased SHP2 expression reduced OS and DFS in patients with urothelial carcinoma, and cervical and endocervical cancer types. Moreover, the elevated expression of SHP2 could also reduce the OS of patients with breast invasive carcinoma, mesothelioma and liver hepatocellular carcinoma. PTPN11 expression was associated with the tumor microenvironment of various tumor types. The tumor mutational burden of various tumor types was associated with microsatellite instability. PTPN11 inhibited T-cell activation and promoted M2 macrophage activation in several tumors. Therefore, SHP2 may be used in the evaluation of tumor progression and prognosis, and it may be an optimal potential biological target for cancer therapy.
由蛋白酪氨酸磷酸酶非受体11型（PTPN11）编码的含Src同源2结构域蛋白酪氨酸磷酸酶（SHP2）在多种人体组织类型中广泛表达，并在多种疾病中发挥重要作用。本研究评估了SHP2对实体瘤发生、发展和预后的影响。从癌症基因组图谱数据库下载了33种癌症类型的转录组测序数据。还下载了相应患者的临床信息、肿瘤突变负荷以及与微卫星不稳定性相关的信息。采用对数秩检验和单变量Cox回归检验评估患者生存率。使用“ESTIMATE”方法评估肿瘤微环境，使用“CIBERSORT”算法评估肿瘤免疫细胞浸润。采用Spearman相关性分析评估SHP2表达与所确定靶点之间的相关性。采用酶联免疫吸附测定法评估乳腺癌、卵巢癌、子宫内膜癌和宫颈癌患者外周血样本中的SHP2表达水平。数据表明，SHP2在多种肿瘤组织中的表达水平升高，且与肿瘤进展和预后相关。在外周血中，乳腺癌（71.43%）和卵巢癌（58.82%）患者的SHP2表达阳性率显著高于相应对照组。然而，子宫内膜癌（31.03%）和宫颈癌（41.30%）患者的SHP2表达阳性率显著低于相应对照组。SHP2表达增加可改善肾透明细胞癌患者的总生存期（OS）和无病生存期（DFS）。然而，SHP2表达增加会降低尿路上皮癌、宫颈癌和宫颈内膜癌患者的OS和DFS。此外，SHP2表达升高还会降低乳腺浸润性癌、间皮瘤和肝细胞癌患者的OS。PTPN11表达与多种肿瘤类型的肿瘤微环境相关。多种肿瘤类型的肿瘤突变负荷与微卫星不稳定性相关。PTPN11在多种肿瘤中抑制T细胞活化并促进M2巨噬细胞活化。因此，SHP2可用于评估肿瘤进展和预后，可能是癌症治疗的一个最佳潜在生物学靶点。
