Tumor Biology - Volume 46, issue 1

Authors: Foda, Abd AlRahman Mohammad | El-Hawary, Amira Kamal | Elnaghi, Khaled | Eldehna, Wesal M. | Enan, Eman T.

Article Type: Research Article

Abstract: BACKGROUND: It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling pathway is activated by different extracellular signals involving the “mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)”, and this induces the expression of genes involved in proliferation and cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts as a potential metastasis regulator through inhibiting the cellular transition to amoeboid behavior in different cancer types. OBJECTIVE: The aim of the study was to investigate the pattern of immunohistochemical expression …of MEK1 and DIAPH3 in colorectal adenoma (CRA) and corresponding colorectal carcinoma (CRC) specimens. METHODS: The immunohistochemical expression of DIAPH3 and MEK1 was examined in 43 cases of CRC and their associated adenomas using tissue microarray technique. RESULTS: MEK1 was overexpressed in 23 CRC cases (53.5%) and in 20 CRA cases (46.5%). DIAPH3 was overexpressed in 11 CRA cases (about 29%) which were significantly lower than CRC (22 cases; 58%) (P  = 0.011). Both MEK1 and DIAPH3 overexpression were significantly correlated in CRC (P  = 0.009) and CRA cases (P  = 0.002). Tumors with MEK1 overexpression had a significantly higher tumor grade (P  = 0.050) and perineural invasion (P  = 0.017). CONCLUSIONS: Both MEK1 and DIAPH3 are overexpressed across colorectal ACS with strong correlation between them. This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process. Show more

Keywords: MEK1, DIAPH3, colorectal adenoma-carcinoma sequence

DOI: 10.3233/TUB-230038

Citation: Tumor Biology, vol. 46, no. 1, pp. 1-11, 2024

Authors: Tishe, Zasia Hossain | Shawkat, Sanjana | Popy, Meherun Nessa | Mumu, Sadia Biswas | Ferdous, Annur | Raisa, Munira Jahan | Hasan, Mehedi | Sultana, Taposhi Nahid | Chaity, Nusrat Islam | Apu, Mohd Nazmul Hasan | Mostaid, Md Shaki

Article Type: Research Article

Abstract: BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is among the vital pro-inflammatory cytokines that potentially exerts a significant influence on the immune response, hence potentially regulating the advancement of cervical lesions. OBJECTIVE: Our study objective was to examine the relationship between two single nucleotide polymorphisms (SNPs) (rs1799724 and rs1800629) of TNF-α and the risk of cervical cancer in women from Bangladesh. METHODS: We recruited 133 patients with cervical cancer and 126 healthy individuals for this study. Genotyping was performed using real-time PCR SNP genotyping assay. Multivariate logistic regression analysis was used to determine the odds ratio (OR) along …with 95% confidence intervals (CI) and p -values. RESULTS: For rs1799724 (C > T) polymorphism, TT mutant homozygous genotype carried 3.26 times increased risk of developing cervical cancer (OR = 3.26, 95% CI = 1.15–9.28, p  = 0.027). Polymorphism of rs1800629 (G > A) was also related to an elevated risk of cervical cancer. Individuals with the AG heterozygous genotype (OR = 2.85, 95% CI = 1.20–6.74, p  = 0.017) and AA mutant homozygous genotype (OR = 4.55, 95% CI = 1.24–16.60, p  = 0.022) also had a higher likelihood of having cervical cancer. Moreover, we found that injectable contraceptives increase the risk of cervical cancer. Individuals who smoked and/or had first-degree relatives with cancer were more likely to carry the risk allele, which increases the likelihood of developing cervical cancer. CONCLUSION: TNF-α polymorphisms in rs1799724 and rs1800629 increase the susceptibility of developing cervical cancer in women from Bangladesh. Show more

Keywords: Bangladesh, TNF-alpha, cervical cancer, rs1800629, rs1799724

DOI: 10.3233/TUB-240002

Citation: Tumor Biology, vol. 46, no. 1, pp. 13-24, 2024