Overexpression of the Oncogenic Variant (KLF6-SV1) in Young NPC Patients and Correlation with Lack of E-Cadherin.

PURPOSE: The transcription factor Krüppel-like factor 6 (KLF6) regulates various cellular functions, such as metabolism, cell proliferation, and differentiation. KLF6 plays a key role in the development and progression of multiple human cancers. METHODS: Fifty primary biopsies and 10 normal nasopharyngeal mucosae were used to analyze by RT-QPCR the expression and the copy number of wtKLF6 and the spliced variants (KLF6-SV1, KLF6-SV2, and KLF6-SV3) in Tunisian patients with nasopharyngeal carcinoma. The expression analysis of E-cadherin and cyclin D1 was conducted by RT-QPCR and Western blot, respectively. RESULTS: The wtKLF6 was significantly downexpressed in tumors compared to normal tissues (p = 0.0015), whereas KLF6-SV1 and KLF6-SV2 were overexpressed in tumors compared to wtKLF6 and KLF6-SV3 (p < 0.0001). Copy number variation was reduced in tumors compared to normal tissues (p = 0.0071). Interestingly, KLF6-SV1 is associated with the juvenile form (p = 0.0003) which is more aggressive than the adult form of NPC. Furthermore, the oncogenic variant KLF6-SV1 was overexpressed in tumors lacking the expression of E-cadherin (p = 0.0022) suggesting its role in metastasis and tumor progression. The wtKLF6 is associated negatively with cyclin D1 in tumor tissues (p = 0.048). CONCLUSION: The wtKLF6 was downexpressed in contrast with the oncogenic variants. Overexpression of KLF6-SV1 is associated with young patients, and loss of E-cadherin suggests that this variant correlated with the aggressiveness of NPC.

CpG methylation of APC promoter 1A in sporadic and familial breast cancer patients.

Tumour suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer initiation. The aim of this study was to assess the extent of methylation of APC gene promoter in 91 sporadic and 44 familial cases of Tunisian patients with breast cancer (BC) in. The frequency of APC promoter methylation is somewhat similar for sporadic and familial breast cancer cases, (52.1%, and 54.5% respectively). For sporadic breast cancer patients, there was a significant correlation of APC promoter hypermethylation with TNM stage (p = 0.024) and 3-year survival (p = 0.025). Regarding the hormonal status (HR), we found significant association between negativity to PR and unmethylated APC (p= 0.005) while ER and Her2/neu are not correlated. Moreover, unmethylated APC promoter is more frequent in tumours expressing at least one out the 3 proteins compared to triple negative cases (p= 0.053). 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. Moreover, patients with sporadic breast cancer displaying the unmethylated profile have a significant prolonged overall survival compared to those with the methylated pattern of APC promoter (p log rank = 0.008). Epigenetic change at the CpG islands in the APC promoter was associated with the silence of its transcript and the loss of protein expression suggesting that this event is the main mechanism regulating the APC expression in breast cancer. In conclusion, our data showed that the loss of APC through aberrant methylation is associated with the aggressive behavior of both sporadic and familial breast cancer in Tunisian patients.