90-Gene Expression Profiling for Tissue Origin Diagnosis of Cancer of Unknown Primary

Cancer of unknown primary (CUP), in which metastatic diseases exist without an identifiable primary location, accounts for about 3–5% of all cancer diagnoses. Successful diagnosis and treatment of such patients are difficult. This study aimed to assess the expression characteristics of 90 genes as a method of identifying the primary site from CUP samples. We validated a 90-gene expression assay and explored its potential diagnostic utility in 44 patients at Jiangsu Cancer Hospital. For each specimen, the expression of 90 tumor-specific genes in malignant tumors was analyzed, and similarity scores were obtained. The types of malignant tumors predicted were compared with the reference diagnosis to calculate the accuracy. In addition, we verified the consistency of the expression profiles of the 90 genes in CUP secondary malignancies and metastatic malignancies in The Cancer Genome Atlas. We also reported a detailed description of the next-generation coding sequences for CUP patients. For each clinical medical specimen collected, the type of malignant tumor predicted and analyzed by the 90-gene expression assay was compared with its reference diagnosis, and the overall accuracy was 95.4%. In addition, the 90-gene expression profile generally accurately classified CUP into the cluster of its primary tumor. Sequencing of the exome transcriptome containing 556 high-frequency gene mutation oncogenes was not significantly related to the 90 genes analysis. Our results demonstrate that the expression characteristics of these 90 genes can be used as a powerful tool to accurately identify the primary sites of CUP. In the future, the inclusion of the 90-gene expression assay in pathological diagnosis will help oncologists use precise treatments, thereby improving the care and outcomes of CUP patients.

Temporal and Spatial Expression Characteristics of MiR-155 and Rheb/mTOR Signaling Pathway in Ischemia–Reperfusion Injury of Rats

Backgrouds: Stroke is the second most prevalent cause of death and the first cause of longterm disability worldwide. Inhibition of miR-155 was found playing a protective role in ischemic stroke, one possible mechanism was regulating Ras-homolog enriched in brain (Rheb)/mammalian target of rapamycin (mTOR) pathway. For possible specific intervention strategy, further exploring the expression characteristics of miR-155 and mRNAs of the Rheb/mTOR pathway in ischemic stroke is neccesary. Results: Our results demonstrated that the infarction volume decreased with the prolongation of the reperfusion in the MCAO/R model rats (P < 0.05). Meanwhile, the miR155 expression obviously increased in both the ischemic core and the ischemic penumbra (IP) area of the model rats, but this trend weakened as the reperfusion time increased. Besides, the expression of mRNAs of Rheb, mTOR, S6kb1, and 4Ebp1 seemed to increase in both the ischemic core and the IP area of the model rats.Interestingly, the mRNA level of S6kb1 obviously increased of all model groups in both the ischemic core and the IP area (P < 0.05),while the mRNA levels of Rheb, mTOR, and 4Ebp1 increased in the first 24 h and rapidly decreased after 48 h and as a result, a statistically significant difference was found only in the 48-h group (P < 0.05). Conclusion: Along with the shrinked infarct volume, the levels of miR-155 decreased and the S6kb1 mRNA level increased as the leghtening of re-perfusion, as to the mRNA levels of Rheb, mTOR, and 4Ebp1,statistical significance was found only in the 48-h group. Unexpectedly, there was no difference between the ischemic core and the IP area for all the above molecules.Indicating that intervention measures targeting to miR155 should be taken systemicly as early as possible after stroke onset,especially within the early 48 hours.