ABSTRACT
Background: Endoscopic submucosal dissection (ESD) has become the preferred treatment of early colorectal cancer. PDCD4 and autophagy have important clinical significance in the pathogenesis of colorectal cancer. Aims: To explore the expressions and significance of apoptosis factor PDCD4 and autophagy factors LC3Ⅱ and p62 in colorectal cancer. Methods: Fifty-four early colorectal adenocarcinoma patients treated by ESD from Jan. 2015 to Nov. 2020 at Binzhou Medical University Hospital were collected. The expressions of PDCD4, LC3Ⅱ and p62 were detected by immunohistochemistry, and the correlations with clinicopathological factors were analyzed. The differential expression of PDCD4 in pan-cancer was analyzed by bioinformatics analysis. Results: Expression of PDCD4 was associated with the long-diameter of paracancer adenoma (P<0.05), and expressions of LC3Ⅱ and p62 were associated with the long-diameters of adenocarcinoma and paracancer adenoma (P<0.05). The positive expression of PDCD4 in P-NIMM was located in the nucleus, while the positive expression in adenocarcinoma was located in cytoplasm. The nucleus/cytoplasm ratio of PDCD4 was significantly higher in P-NIMM than in P-LGIN, P-HGIN and adenocarcinoma (P<0.05), and the nucleus/cytoplasm ratio of PDCD4 was significantly higher in P-LGIN, P-HGIN than in adenocarcinoma (P<0.05). The positive expression rates of LC3Ⅱ and p62 were significantly higher in adenocarcinoma than in P-NIMM and P-LGIN (P<0.05). In P-LGIN, P-HGIN and adenocarcinoma, the expression of PDCD4 was negatively correlated with the expressions of LC3Ⅱ and p62 (P<0.05). The bioinformatics analysis showed that expression of PDCD4 was significantly reduced in a variety of malignant tumors including colorectal cancer (P<0.05). Conclusions: The inhibition of apoptosis and activation of autophagy may promote the occurrence of colorectal cancer, and its mechanism may be related to the intracellular transposition of PDCD4 that inhibits cell apoptosis and enhances autophagy, and activating cellular autophagy may further accelerate the degradation of PDCD4 and thus reducing its cancer inhibiting effect.
ABSTRACT
Purpose To investigate the expression of Beclin1, LC3 and mTOR in colorectal cancer ( CRC) and their significance. Methods Immunohistochemistry, Western blot and real-time PCR were employed to detect the expression of Beclin1, LC3 and mTOR in CRC. Results The positive expression rate of Beclin1, LC3 and mTOR in 242 cases of CRC was 90. 50%, 87. 19% and 46. 28%, respectively, which were higher than that in adjacent tissues ( P0. 05). The expres-sion of LC3 was positively correlated with Beclin1 and negatively correlated with mTOR in colorectal cancer (rs =0. 593, P0. 05). Kaplan-Meier survival analysis re-vealed that the five-year survival rate of patients without nodal metastasis, positive expression of Beclin1, LC3 and negative expression of mTOR was higher than those with nodal metastasis, negative expression of Beclin1 and LC3, and positive expression of mTOR. Cox survival analysis results revealed that LC3, mTOR and lymphnode metastasis were independent prognostic factors. The results of IHC, real-time PCR and Western blot in fresh CRC tissues indicated that the expression of Beclin1, LC3 and mTOR in colorectal cancer was significantly higher than that in adjacent tissues (P<0. 05). Conclusions The aberrant expression of Beclin1, LC3 and mTOR may be associated with the development and progression of colorectal cancer. The simultaneous detection of Beclin1, LC3 and mTOR genes in colorectal cancer may be helpful for the evaluation of the progressive degree and the judgment of prognosis.