Mechanistic analysis demonstrated that miR-106a-3p specifically targeted the adenomatous polyposis coli (APC) gene, and LINC01133/miR-106a-3p suppressed the EMT and metastasis by inactivating the Wnt/β-catenin pathway in an APC-dependent manner.
On the other hand, aberrant methylation of APC was associated with tumour size (p = 0.036), lymph node (p = 0.028), distant metastasis (p = 0.031), and 3-year survival (p = 0.046) in the group of patients with familial breast cancer.
The significant associations of mutations were KRAS with age less than 60 years (p = 0.041), PIK3CA with males (p = 0.032), tumor stage I-II (p = 0.013), lack of metastasis in lymph nodes (p = 0.040), NRAS with rectum (p = 0.002), and APC with T2 stage of tumor growth (p = 0.013).
APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis.
The variables associated with a shorter time to metastases/recurrence were gastrointestinal histology (P = 0.004), APC (P = 0.008), PTEN (P = 0.026) and TP53 (P = 0.044) alterations.
Analysis of patient-matched primary carcinomas and metastases showed overexpression of APC (p=0.022), MAPK3 (p=0.002) and BNIP3 (p=0.004) in the former.
For example, the methylation of the tumor suppressor gene APC was strongly associated with a specific subset of tumors that were both ER+ and HER2+, while methylation of the TWIST oncogene was associated with breast cancers that did not metastasize.
p53 overexpression was more frequently observed in advanced gastric carcinoma and lymph node metastasis than in early carcinoma or in the absence of metastasis (p < 0.05). p21 loss was positively correlated with APC loss, but inversely correlated with beta-catenin nuclear accumulation and NF-kappaB positivity (p < 0.05).
Our hypothesis, which has received recent experimental support, is that the mechanism that links abnormalities at the gene level (eg, APC mutations) and abnormalities at the tissue level (eg, proliferative shift, dysplasia, carcinoma) from cancer initiation to metastasis is SC overpopulation.
Of the 64 genes, 11 are related to cancer metastasis (APC, CDH8, IL8RB, LY6D, PCDHGA12, DSP, NID, ENPP2, CCR2, CASP8, and CASP10) and eight are involved in apoptosis (CASP8, CASP10, PIK3R1, BCL2, SON, INHA, PSEN1, and BIK).
Molecular changes in the Ki-ras and APC genes in primary colorectal carcinoma and synchronous metastases compared with the findings in accompanying adenomas.
Highly invasive tumours with synchronous metastases (Dukes' stage D) had, instead, a low frequency of APC mutations (20%, 2/10) (P = 0.02, compared with Dukes' stages A, B and C).
The main goal of this study was to examine the expression of DNA mismatch repair genes (MLH1, MSH2, PMS1 and PMS2), the adenomatous polyposis coli (APC) gene and growth arrest DNA damage inducible (GADD) genes (GADD34, GADD45 and GADD153) in the different stages of melanoma recurrences and metastases, and to identify any mutual consistencies in their expression pattern.
Seven samples of 32 heterozygous persons of APC gene (three out of seven eccrine poromas, two eccrine porocarcinomas and two metastatic tumors of rectal adenocarcinoma) showed for LOH in the APC gene.
We investigated adrenal and metastatic tumors for loss of heterozygosity affecting four genetic loci containing the tumor suppressor genes p53, RB, DCC, and APC, using polymerase chain reaction and restriction fragment length polymorphism assay.