AUTHOR=Luo Kangjia , Song Yanni , Guan Zilong , Ou Suwen , Ye Jinhua , Ran Songlin , Wang Hufei , Tao Yangbao , Gong Zijian , Ma Tianyi , Jin Yinghu , Huang Rui , Gao Feng , Yu Shan
TITLE=A KRAS-Associated Signature for Prognostic, Immune and Chemical Anti-Cancer Drug-Response Prediction in Colon Cancer
JOURNAL=Frontiers in Pharmacology
VOLUME=13
YEAR=2022
URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.899725
DOI=10.3389/fphar.2022.899725
ISSN=1663-9812
ABSTRACT=Background: KRAS mutation, one of the most important biological processes in colorectal cancer, leads to poor prognosis in patients. Although studies on KRAS have concentrated for a long time, there are currently no ideal drugs against KRAS mutations.
Methods: Different expression analysis and weighted gene coexpression network analysis was conducted to select candidate genes. Log-rank tests and Cox regression picked out the prognostic genes to build a KRAS-related gene prognostic score (KRGPS). A nomogram based on KRGPS was built to predict survival of clinical patients. Comprehensive analysis showed the prognosis, immune microenvironment and response to immune therapy and chemotherapy in KRGPS subgroups.
Results: We collected a KRGPS from the set of two genes GJB6 and NTNG1, with low-KRGSP patients having better progression-free survival (PFS). Low KRGPS is correlated with high infiltration of activated NK cells, plasma cells and activated memory CD4 T cells and that these cells benefit more from immune checkpoint inhibitor therapy. However, high KRGPS is associated with high infiltration of activated mast cells, pathways of immune dysregulation and a high ratio of TP53 and KRAS mutations. KRGPS subgroups are also sensitive to chemotherapy differently. A nomogram, established based on the KRGPS and pathological stage, predict 3- and 5-years PFS well.
Conclusions: The KRAS-associated score acts as a promising signature to distinguish prognosis, molecular and immune characteristics, and benefits from immune and chemical therapy. These KRAS-associated genes could be promising targets for drug design.