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. 2021 Aug;12(4):1577-1589.
doi: 10.21037/jgo-21-403.

Expression, clinical significance and correlation of RUNX3 and HER2 in colorectal cancer

Yunshi Wu  1 , Jun Xue  2 , Yuanrui Li  3 , Xueliang Wu  2 , Ming Qu  2 , Dandan Xu  4 , Yongquan Shi  4
Affiliations

Expression, clinical significance and correlation of RUNX3 and HER2 in colorectal cancer

Yunshi Wu et al. J Gastrointest Oncol. 2021 Aug.

Abstract

Background: The incidence of colorectal cancer is high and on the rise. The genetic and protein expressions of RUNT-associated transcription factor 3 (RUNX3) and human epidermal growth factor receptor 2 (HER2) in colorectal cancer (CRC) and adjacent normal tissues were detected to preliminarily explore their correlation and clinical significance.

Methods: CRC specimens excised during general surgery were selected for localization and quantitative analysis of protein and gene expression by SP (Streptavidin-peroxidase conjugated method) immunohistochemical staining, reverse transcription-polymerase chain reaction (RT-qPCR) and western blot. Combined with the patients' data, the relationship between the expression of the two genes and tumor characteristics was analyzed. Log-rank test was used to analyze the correlation between the two proteins and survival prognosis of CRC patients. The expression of RUNX3 in RKO and HCT-116 was knocked down, and the relative expression of HER2 in the two cell lines was detected.

Results: Immunohistochemical, RT-qPCR and Western blot results showed that the positive expression rate of RUNX3 in CRC was lower than in the normal group, and HER2 in CRC was higher than in the normal group. The positive expression of the two proteins correlated with the pT and pN stages of CRC. A significant negative correlation between the expression of the two genes in CRC. Follow-up results showed that the number of Runx3-positive patients was higher than negative ones, while HER2 positive were fewer than negative ones. In vitro experiments showed that RUNX3 protein and gene expression decreased, HER2 protein and gene expression increased in RUNX3 knockdown RKO and HCT-116 cells, respectively (P<0.05).

Conclusions: The expression of RUNX3 and HER2 in CRC is related to the occurrence and development of CRC, and the two genes have a negative regulating effect.

Keywords: Colorectal cancer (CRC); HER2; RUNX3; molecular markers.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-403). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Hematoxylin-eosin staining of (A) normal tissue, (B) cancer tissue. Immunohistochemical SP staining of (C) RUNX3 staining in normal tissues; (D) low RUNX3 expression in cancer tissue; (E) high RUNX3 expression in cancer tissue; (F) low HER2 expression in cancer tissue; (G) HER2 staining in normal tissue; (H) high HER2 expression in cancer tissue.
Figure 2
Figure 2
RT-qPCR amplification and dissolution curves. (A) RT-qPCR amplification curve; (B) RT-qPCR dissolution curve. RT-qPCR, reverse transcription-polymerase chain reaction.
Figure 3
Figure 3
RUNX3 and HER2 mRNA relative expression (A) RUNX3 mRNA relative expression; (B) HER2 mRNA relative expression. *, P<0.05; **, P<0.01.
Figure 4
Figure 4
RUNX3 HER2 protein relative expressions. ***, P<0.001.
Figure 5
Figure 5
Relationship of (A) RUNX3 expression and (B) HER2 expression with DFS. DFS, disease-free survival.
Figure 6
Figure 6
Correlation between RUNX3 and HER2 expression in CRC tissue. CRC, colorectal cancer.
Figure 7
Figure 7
Si-RUNX3 transfected in RKO and HCT-116. (A,B) Bright field, (C,D) dark field. Magnification: ×200.
Figure 8
Figure 8
Knockdown efficiency of si-RUNX3 in RKO. ***, represent for P<0.001.
Figure 9
Figure 9
RUNX3, HER2 protein (A-D) and mRNA (E,F) relative expression in RKO and HCT-116. *, P<0.05; ***, P<0.001.
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