Laterality influence on gene expression of DNA damage repair in colorectal cancer

Abstract

Colorectal carcinoma (CRC) is the third most common malignancy worldwide, and second in number of deaths in the world. The molecular pathogenesis of CRC is heterogeneous and can affect several genes. Moreover, genomic instability is recognized as an important part of CRC carcinogenesis and is tightly connected to DNA damage response. DNA damage repair (DDR) pathways are intrinsically associated with cancer development and establishment. Traditionally, CRC is considered as one coherent disease, however, new evidence shows that left and right-sided CRC present differences observed in clinical settings, as well as in pre-clinical studies. Therefore, this study aimed to investigate the impact of DDR transcriptional profiles on survival in different sublocations of the colon and rectum using Cox regression, survival analysis and differential gene expression. Right side colon (RSC) has DDR genes’ expression associated only with higher risk of death, while left side colon (LSC) and Rectum have most genes’ expression associated with lower risk. The pattern is the same with survival analysis. All significant DDR genes had lower expression associated with better survival in RSC, as opposed to LSC and Rectum. Our results demonstrate that RSC is distinctively different from LSC and Rectum. LSC and Rectum have similar DDR expression profiles.

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…This study and others have shown that KRAS mutation was more frequent in right sided CRC [37, 54, 55]. The predilection of KRAS mutations for the right side of the colon may be influenced by the fact that the right and left side of the colon have different biology and histopathology in their respective embryological origins [37, 56, 57]. Right-sided CRC often has flat histopathology and a DNA mismatch repair pathway deficiency [58].…”

High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations

“…This study and others have shown that KRAS mutation was more frequent in right-sided CRC [ 48 , 72 , 73 ]. The predilection of KRAS mutations for the right side of the colon may be influenced by the fact that the right and left sides of the colon have different biology and histopathology in their respective embryological origins [ 48 , 74 , 75 ]. Right-sided CRC often has flat histopathology and a DNA MMR pathway deficiency [ 76 ].…”