Published online Feb 21, 2019. doi: 10.3748/wjg.v25.i7.808
Peer-review started: November 14, 2018
First decision: December 5, 2018
Revised: January 17, 2019
Accepted: January 20, 2019
Article in press: January 20, 2019
Published online: February 21, 2019
The RAS signaling pathway plays a crucial role in the invasiveness and metastasis of tumor cells. Mutations in any one of the upstream genes (such as the RAS gene) may be transmitted to the protein through transcription or translation, resulting in abnormal activation of the signaling pathway. Patients with KRAS gene mutation have a poor prognosis. This study investigated the effect of KRAS mutations on its associated proteins in colorectal cancer. It is helpful to understand the cause of tumor progression and drug resistance caused by mutation of the KRAS gene.
By analyzing the effect of upstream gene mutation on the downstream protein expression of signal pathway, it is helpful to further understand the cause of drug resistance. Future studies should focus on the active forms and structures of signal molecules, and find out which forms and conformational proteins are active, which is conducive to the synthesis of corresponding targeted drugs.
The main goal was to find out which forms and conformational proteins are active. At present, it is found that the amount of protein is not the main factor affecting the activity. Achieving these goals can help to develop targeted therapies.
In this study, the mutation of the KRAS gene was analyzed by real-time quantitative polymerase chain reaction, protein expression was analyzed by immunohistochemistry, and the impact of gene mutation on protein expression, the effect of gene and protein on prognosis, and the relationship between protein expression and clinicopathology were analyzed.
KRAS gene status had no significant effect on RAS pathway signaling molecules in colorectal cancer. Positive expression of KRAS and ERK was associated with poor tumor differentiation. MEK expression was associated with more distant metastasis. The 4-year progression-free survival rate was significantly higher in patients with KRAS-negative tumors than in those with KRAS-positive tumors. Multivariate analysis showed that only the expression of KRAS protein was a risk factor for tumor recurrence. These results are consistent with observations in clinical practice, indicating the credibility of the study. The specific reasons for the genetic and protein effects of these results need to be further clarified.
In this study, the relationship between the KRAS gene and the RAS signaling pathway molecule was discussed. It was found that the gene-to-protein to functional change was a complex process, and the gene mutation did not cause an increase in the positive rate of downstream protein expression. KRAS protein was found to be involved in tumor differentiation and prognosis. The study also found that the farther apart the molecules in the signal pathway, the smaller the effect, suggesting that the signaling pathways are intertwined. The combination of targeted drugs and multi-channel blockade is better than single-channel blockade.
The study began without considering the phosphorylation of the signal molecule and the effect of structure on function. Future research is best to study the effect of phosphorylation and spatial structure changes of a certain signal molecule on function. Using atomic force microscopy and mass spectrometry and cryo-electron microscopy equipment and electron microscopy negative staining preparation methods to observe the spatial structure of individual lipoprotein molecules can find which conformational proteins are active.