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Low expression of PKC α and high expression of KRAS predict poor prognosis in patients with colorectal cancer

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ABSTRACT

The current study aimed to determine the association between protein kinase Cα (PKCα) and Kirsten rat sarcoma viral oncogene homolog (KRAS) expression and the response to folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX regimen) in patients with colorectal cancer (CRC). The protein levels of PKCα and KRAS were analyzed by immunohistochemistry in tissue samples from patients with CRC and in non-cancerous tissues, including 152 cases of colorectal adenocarcinoma, 30 cases of colorectal adenoma and 20 normal colonic mucosa samples. The association between PKCα and KRAS expression and clinicopathological features was analyzed. The rates of positive PKCα protein expression in patients with poorly, moderately and well-differentiated adenocarcinoma were 16.7% (6/36), 40.0% (24/60), and 57.1% (32/56), respectively (P<0.013). The rate of positive KRAS expression in CRC patients was significantly higher than in patients with colon adenoma and normal colon mucosa (P<0.001). Expression levels of KRAS were associated with the degree of differentiation of CRC (P<0.001). Expression of PKCα was negatively correlated with KRAS expression in CRC tissues. The mean progression-free survival (PFS) times in patients with high and low expression of PKCα were 43.9 and 38.8 months, respectively (P<0.001). The mean PFS times were 38.5 and 45.5 months in patients with high and low expression of KRAS, respectively (P=0.001). In conclusion, low PKCα and high KRAS expression predicted relatively poor prognosis in patients with CRC.

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Representative immunohistochemistry images of PKCα (left column) and KRAS (right column) staining in adenocarcinoma, colon adenoma and normal colon mucosa. (A and B) Minimally-differentiated adenocarcinoma; (C and D) moderately-differentiated adenocarcinoma; (E and F) well-differentiated adenocarcinoma; (G and H) colon adenoma; (I and J) normal colon mucosa. PKCα, protein kinase Cα; KRAS, Kirsten rat sarcoma viral oncogene homolog.
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f1-ol-0-0-4845: Representative immunohistochemistry images of PKCα (left column) and KRAS (right column) staining in adenocarcinoma, colon adenoma and normal colon mucosa. (A and B) Minimally-differentiated adenocarcinoma; (C and D) moderately-differentiated adenocarcinoma; (E and F) well-differentiated adenocarcinoma; (G and H) colon adenoma; (I and J) normal colon mucosa. PKCα, protein kinase Cα; KRAS, Kirsten rat sarcoma viral oncogene homolog.

Mentions: PKCα was located in the cytoplasm and cell membrane and was observed as brown granules (Fig. 1). The rate of positive expression of PKCα in CRC tissues was significantly lower than that in colorectal adenoma and normal colorectal mucosa tissues (P=0.018; Table I). KRAS immunoreactivity was observed in the cytoplasm (Fig. 1). The KRAS protein expression rate in CRC tissues was significantly higher compared with that in colon adenoma and normal colon mucosa tissues (P=0.006) (Table I).


Low expression of PKC α and high expression of KRAS predict poor prognosis in patients with colorectal cancer
Representative immunohistochemistry images of PKCα (left column) and KRAS (right column) staining in adenocarcinoma, colon adenoma and normal colon mucosa. (A and B) Minimally-differentiated adenocarcinoma; (C and D) moderately-differentiated adenocarcinoma; (E and F) well-differentiated adenocarcinoma; (G and H) colon adenoma; (I and J) normal colon mucosa. PKCα, protein kinase Cα; KRAS, Kirsten rat sarcoma viral oncogene homolog.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998155&req=5

f1-ol-0-0-4845: Representative immunohistochemistry images of PKCα (left column) and KRAS (right column) staining in adenocarcinoma, colon adenoma and normal colon mucosa. (A and B) Minimally-differentiated adenocarcinoma; (C and D) moderately-differentiated adenocarcinoma; (E and F) well-differentiated adenocarcinoma; (G and H) colon adenoma; (I and J) normal colon mucosa. PKCα, protein kinase Cα; KRAS, Kirsten rat sarcoma viral oncogene homolog.
Mentions: PKCα was located in the cytoplasm and cell membrane and was observed as brown granules (Fig. 1). The rate of positive expression of PKCα in CRC tissues was significantly lower than that in colorectal adenoma and normal colorectal mucosa tissues (P=0.018; Table I). KRAS immunoreactivity was observed in the cytoplasm (Fig. 1). The KRAS protein expression rate in CRC tissues was significantly higher compared with that in colon adenoma and normal colon mucosa tissues (P=0.006) (Table I).

View Article: PubMed Central - PubMed

ABSTRACT

The current study aimed to determine the association between protein kinase Cα (PKCα) and Kirsten rat sarcoma viral oncogene homolog (KRAS) expression and the response to folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX regimen) in patients with colorectal cancer (CRC). The protein levels of PKCα and KRAS were analyzed by immunohistochemistry in tissue samples from patients with CRC and in non-cancerous tissues, including 152 cases of colorectal adenocarcinoma, 30 cases of colorectal adenoma and 20 normal colonic mucosa samples. The association between PKCα and KRAS expression and clinicopathological features was analyzed. The rates of positive PKCα protein expression in patients with poorly, moderately and well-differentiated adenocarcinoma were 16.7% (6/36), 40.0% (24/60), and 57.1% (32/56), respectively (P<0.013). The rate of positive KRAS expression in CRC patients was significantly higher than in patients with colon adenoma and normal colon mucosa (P<0.001). Expression levels of KRAS were associated with the degree of differentiation of CRC (P<0.001). Expression of PKCα was negatively correlated with KRAS expression in CRC tissues. The mean progression-free survival (PFS) times in patients with high and low expression of PKCα were 43.9 and 38.8 months, respectively (P<0.001). The mean PFS times were 38.5 and 45.5 months in patients with high and low expression of KRAS, respectively (P=0.001). In conclusion, low PKCα and high KRAS expression predicted relatively poor prognosis in patients with CRC.

No MeSH data available.


Related in: MedlinePlus