In all 16,182 metastatic cancers and 26,480 early primary cancers, PTPRT non-silent mutations occurred in at least five metastatic cancers in six type of cancers, corresponding to 10,068 of metastatic cancer samples and 13,487 early primary cancer samples, respectively. These 23,555 samples were used for further differential analysis (Table 1). Among the six types of cancer, PTPRT mutations were significantly enriched in metastatic cancer (Figure 1, A-F, p<0.05, q < 0.05), except that q-value was not significant in melanoma due to the small number of primary cancer tissue samples (Figure 1E, 14 / 1148 vs 0 / 669, q = 0.156, p= 0.00097). In breast cancer, the combined mutation of PTPRT and PIK3CA in metastatic breast cancer was significantly higher than in primary tissue (Figure 1A, q = 0.025). In colorectal cancer, as previously reported, the combined mutation of APC-PTPRT, APC-PTPRT-TP53 and PTPRT-TP53 were significantly higher in metastatic colorectal cancer than in primary tissue (Figure 1B, q= 3.4E-05, q= 0.0006 and q=2.6E-06, respectively). In Esophagogastric cancer, the combination of PTPRT and TP53 in metastatic cancer is significantly higher than that in primary tumor tissue (Figure 1C, q=0.023). In NSCLC, the combined mutation of KEAP1-PTPRT, PTPRD-PTPRT-TP53 and PTPRT-TP53 were significantly higher in metastatic NSCLC than in primary tissue (Figure 1D, q= 0.02, q= 0.0097 and q=1.68E-07, respectively).
In summary, by analyzing the mutation data of all 42662 cases from GENIE and cBioPortal databases, we found that PTPRT was not only enriched in metastatic cancer tissues of colorectal cancer, but also in other cancer types, such as esophageal cancer, breast cancer, non-small cell lung cancer and melanoma. This finding suggests that PTPRT mutation may be a molecular marker of cancer metastasis in a variety of cancers, and that simultaneous mutations in PTPRT and other driver genes may be responsible for different cancer metastases. Of course, since we do not have the clinical tracking information of these samples, especially GENIE database has not provided the tumor stage and prognosis information, so all primary cancer samples are counted as non-metastasis, which may make our results tend to be conservative. In general, these data suggest that PTPRT may be closely related to metastasis in multiple cancers, so it is necessary to carry out postoperative adjuvant treatment measures, such as chemotherapy, for tumor patients with PTPRT mutations.