Journal of the Egyptian National Cancer Institute最新文献

Background: A malignancy of the endocrine system, one of the most common types, is thyroid cancer. It is proven that children who receive radiation treatment for leukemia or lymphoma are at a heightened risk of thyroid cancer due to low-dose radiation exposure throughout childhood. Several factors can increase the risk of thyroid cancer (ThyCa), such as chromosomal and genetic mutations, iodine intake, TSH levels, autoimmune thyroid disorders, estrogen, obesity, lifestyle changes, and environmental contaminants.

Objectives: The study aimed to identify a specific gene as an essential candidate for thyroid cancer progression. We might be able to focus on developing a better understanding of how thyroid cancer is inherited.

Methods: The review article uses electronic databases such as PubMed, Google Scholar, Ovid MEDLINE, Embase, and Cochrane Central. The most frequently associated genes with thyroid cancer found on PubMed were BAX, XRCC1, XRCC3, XPO5, IL-10, BRAF, RET, and K-RAS. To perform an electronic literature search, genes derived from DisGeNET: a database of gene-disease associations, including PRKAR1A, BRAF, RET, NRAS, and KRAS, are used.

Conclusion: Examining the genetics of thyroid cancer explicitly emphasizes the primary genes associated with the pathophysiology of young and older people with thyroid cancer. Developing such gene investigations at the beginning of the thyroid cancer development process can identify better outcomes and the most aggressive thyroid cancers.

Background: Breast cancer is the most common female cancer worldwide. Its diagnosis and prognosis remain scanty, imprecise, and poorly documented. Previous studies have indicated that some genetic mutational signatures are suspected to lead to progression of various breast cancer scenarios. There is paucity of data on the role of AI tools in delineating breast cancer mutational signatures. This study sought to investigate the relationship between breast cancer genetic mutational profiles using artificial intelligence models with a view to developing an accurate prognostic prediction based on breast cancer genetic signatures. Prior research on breast cancer has been based on symptoms, origin, and tumor size. It has not been investigated whether diagnosis of breast cancer can be made utilizing AI platforms like Cytoscape, Phenolyzer, and Geneshot with potential for better prognostic power. This is the first ever attempt for a combinatorial approach to breast cancer diagnosis using different AI platforms.

Method: Artificial intelligence (AI) are mathematical algorithms that simulate human cognitive abilities and solve difficult healthcare issues such as complicated biological abnormalities like those experienced in breast cancer scenarios. The current models aimed to predict outcomes and prognosis by correlating imaging phenotypes with genetic mutations, tumor profiles, and hormone receptor status and development of imaging biomarkers that combine tumor and patient-specific features. Geneshotsav 2021, Cytoscape 3.9.1, and Phenolyzer Nature Methods, 12:841-843 (2015) tools, were used to mine breast cancer-associated mutational signatures and provided useful alternative computational tools for discerning pathways and enriched networks of genes of similarity with the overall goal of providing a systematic view of the variety of mutational processes that lead to breast cancer development. The development of novel-tailored pharmaceuticals, as well as the distribution of prospective treatment alternatives, would be aided by the collection of massive datasets and the use of such tools as diagnostic markers.

Results: Specific DNA-maintenance defects, endogenous or environmental exposures, and cancer genomic signatures are connected. The PubMed database (Geneshot) search for the keywords yielded a total of 21,921 genes associated with breast cancer. Then, based on their propensity to result in gene mutations, the genes were screened using the Phenolyzer software. These platforms lend credence to the fact that breast cancer diagnosis using Cytoscape 3.9.1, Phenolyzer, and Geneshot 2021 reveals high profile of the following mutational signatures: BRCA1, BRCA2, TP53, CHEK2, PTEN, CDH1, BRIP1, RAD51C, CASP3, CREBBP, and SMAD3.

Background: The prognostic value of the level of programmed death ligand 1 (PD-L1) expression in non-Hodgkin lymphoma (NHL) is still debatable. This study examined the effect of the level of PD-L1 expression on the clinicopathological characteristics and prognosis of diffuse large B cell lymphoma (DLBCL).

Methods: A retrospective study was conducted on formalin-fixed paraffin-embedded tissue blocks of one hundred de novo DLBCL patients diagnosed from 2013 to 2016. PD-L1 expression was defined by a modified Combined-Positive Score (CPS) and their medical records were reviewed to collect their clinical, laboratory and radiological data, treatment, and outcome.

Results: The included patients were aged from 23 to 85 years and treated by rituximab- cyclophosphamide, doxorubicin, oncovin, prednisone (R-CHOP); 49% were males; 85% of the cases were presented at Ann Arbor stages III, IV; 33% of patients were seropositive for HCV and 87% of cases were presented with intermediate and high IPI. All included cases expressed PD-L1 using modified CPS. 27% of patients showed low PD-L1 expression (≥ 5% to < 50% of total tumor cellularity) while 73% of patients showed high PD-L1expression (≥ 50% of total tumor cellularity). High PD-L1 expression is statistically correlated with advanced stage (p 0.01), high IPI score (p 0.017), high incidence of stationary and progressive disease (p 0.002) and high incidence of relapse (p value 0.01). Five-year disease-free survival (DFS) was 29% for patients with high PD-L1 expression compared with 84.8% for patients with low PD-L1 expression (p 0.001).

Conclusions: This study suggests that high PD-L1 expression in DLBCL is associated with aggressive clinicopathological features and a decreased response to R-CHOP. The level of PD-L1 expression could be an independent predictor of DFS of DLBCL. More research is mandatory to standardize the cutoff value and scoring methods.

Background and aim: Neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) became the standard of care for muscle-invasive bladder cancer (MIBC) in the last few years. We aimed to evaluate the radiological, pathological responses to NAC, and the 30-day surgical outcomes after RC in MIBC.

Patients and methods: A retrospective cohort study involving adult patients with localized urothelial MIBC who received NAC followed by RC at the National Cancer Institute of Egypt (NCI-E) for 2 years (2017 and 2018). Out of 235 MIBC cases, we recognized 72 patients (30%) who fitted the eligibility criteria.

Results: A cohort of 72 patients with a median age of 60.5 years (range 34-87). Hydronephrosis, gross extravesical extension (cT3b), and radiologically negative nodes (cN0) were depicted initially in 45.8, 52.8, and 83.3% of patients, respectively. Gemcitabine and cisplatin (GC) was the rampant NAC employed in 95.8%. Radiological evaluation post NAC using RECIST v1.1 revealed a response rate (RR) of 65.3% in bladder tumor and progressive disease in the former and lymph nodes encountered in 19.4 and 13.9%, respectively. The median time from the end of NAC to surgery was 8.1 weeks (range 4-15). Open RC and ileal conduit were the most common types of surgery and urinary diversion, respectively. Pathological down-staging was encountered in 31.9%, and only 11 cases (15.3%) achieved pathological complete response (pCR). The latter was significantly correlated with the absence of hydronephrosis, low-risk tumors, and associated bilharziasis (p = 0.001, 0.029, and 0.039, respectively). By logistic regression, the high-risk category was the only independent factor associated with a poor likelihood of achieving pCR (OR 4.3; 95% CI 1.1-16.7; p = 0.038). Thirty-day mortality occurred in 5(7%) patients, and 16(22%) experienced morbidity, with intestinal leakage being the most frequent complication. cT4 was the only significant factor associated with post-RC morbidity and mortality compared to cT2 and cT3b (p = 0.01).

Conclusions: Our results are further supporting the radiological and pathological benefits of NAC in MIBC, evidenced by tumor downstaging and pCR. The complication rate after RC is still considerable; hence, more larger studies are necessary to postulate a comprehensive risk assessment tool for patients who would get the maximum benefit from NAC, hoping to accomplish higher complete response rates with ultimately increased adoption of the bladder preservation strategies.

Background: This study was performed to investigate the expression of different biomarkers in patients with hepatocellular carcinoma and its connection with detective biomarkers. To achieve this objective, seventy subjects were examined in this study, sub-grouped to forty HCC patients and thirty HCV-affected patients with matched thirty healthy individuals. The study involved several groups of participants who were matched based on their age and gender.

Methods: The expression pattern of biomarkers was monitored by quantitative polymerase chain reaction (qRT-PCR). Finally, we utilized a ROC curve to investigate the predictive accurateness of those distinct biomarkers as well as a traditional tumor marker, AFP, in detecting HCC cases.

Results: The baseline biomarker expression levels were markedly greater in HCC patients than in those affected by HCV or healthy subjects. We stated that the sensitivity and the specificity of the different biomarkers alone did not improve than that of AFP alone. When comparing AFP with different biomarkers, the diagnostic validity improves only when combining with CK-1.

Conclusions: Overall, our results indicate that CK-1 mRNA expression could help as a noninvasive tumor biomarker for HCC prognosis and diagnosis when combining with AFP.

Background: The therapeutic modalities for nonmetastatic rectal cancer are presently undergoing major changes. The standard treatment is multidisciplinary, combining radiotherapy, chemotherapy, and surgery. The aim of this minireview is to provide an update on the place of organ preservation in the treatment of nonmetastatic rectal cancer in 2022.

Main text: The multimodal strategy based on initial radiochemotherapy followed by radical surgery with excision of the mesorectum has improved oncological results but at the expense of morbidity and sequelae altering life quality. The strategy of rectal preservation has been proposed since the 2000s after the publication of the results of the Brazilian study that proposed a simple surveillance after radiochemotherapy without surgery in good responders. In fact, preoperative radiochemotherapy was able to obtain a complete histological response in 10 to 30% of case. In view of this non-negligible percentage of tumor sterilization, which may well increase with the standardization of total neoadjuvant treatment, a strategy of organ preservation can be proposed in these patients to avoid morbidity and postoperative sequelae.

Short conclusion: This nonoperative approach is currently widely studied in certain patients who have a complete response (clinical, endoscopic, and radiological). However, the selection of these patients is not simple and still complex.

Background: Health-related quality of life has emerged as a significant component in pediatric oncology research during the last several decades. Measures of health-related quality of life provide a thorough assessment of the child's response to medical therapy, disease course, and adjustment outcomes in the context of pediatric oncology.

Methods: The aim of the present study was to assess the cancer-specific health-related quality of life in cancer pediatric patients and to evaluate the contribution of its domains and some of the anthropometric, sociodemographic, and treatment-related variables on the overall quality of life, by using the PedsQL™ 3.0 Cancer Module.

Results: The study included 110 cases. The mean value of the PedsQL™ 3.0 Cancer Module score was 49.3 ± 12.0. The lowest mean score of quality of life was for the "procedure anxiety" (8.7 ± 23.9), followed by the "worry" domains (16.6 ± 28.5). Higher "frequency of hospital visits" was associated with increased feeling of pain and treatment anxiety yet decrease in suffering from nausea and vice versa. The longer period of hospital admission for more than half of the recommended treatment period was associated with reduced pain suffering on the expense of increase in feeling of worry as well as communication problems. The perceived physical appearance was better among those patients who spent a treatment period for 3-6 months when compared to those who spent a treatment period less than 3 months or more than 6 months. There was a highly significant association between all the eight-cancer-specific quality-of-life domains except the pain domain- and the overall quality-of-life log scores. Nausea problem followed by worry and cognitive problems was the most effective domains on the overall quality-of-life score.

Conclusion: Cancer pediatric patients suffered low quality of life especially for anxiety procedure and worry domains with special consideration for the impact of nausea, worry, and cognitive problems on their perception of quality of life.

Background: Gastric cancer is a dominant source of cancer-related death around the globe and a serious threat to human health. However, there are very few practical diagnostic approaches and biomarkers for the treatment of this complex disease.

Methods: This study aimed to evaluate the association between differentially expressed genes (DEGs), which may function as potential biomarkers, and the diagnosis and treatment of gastric cancer (GC). We constructed a protein-protein interaction network from DEGs followed by network clustering. Members of the two most extensive modules went under the enrichment analysis. We introduced a number of hub genes and gene families playing essential roles in oncogenic pathways and the pathogenesis of gastric cancer. Enriched terms for Biological Process were obtained from the "GO" repository.

Results: A total of 307 DEGs were identified between GC and their corresponding normal adjacent tissue samples in GSE63089 datasets, including 261 upregulated and 261 downregulated genes. The top five hub genes in the PPI network were CDK1, CCNB1, CCNA2, CDC20, and PBK. They are involved in focal adhesion formation, extracellular matrix remodeling, cell migration, survival signals, and cell proliferation. No significant survival result was found for these hub genes.

Conclusions: Using comprehensive analysis and bioinformatics methods, important key pathways and pivotal genes related to GC progression were identified, potentially informing further studies and new therapeutic targets for GC treatment.

Background: Driver molecular aberrations, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement, play an important role in the oncogenesis and progression of non-squamous non-small-cell lung cancers (NSCLC). Therefore, this study aimed to detect the incidence of driver mutations among non-squamous NSCLC.

Patients and methods: This was a retrospective-prospective cohort study on 131 patients with non-squamous NSCLC. Data on age, smoking status, chest symptoms, method of lung cancer diagnosis, molecular testing, including EGFR mutations in formalin-fixed paraffin-embedded (FFPE) tumor tissue and serum circulating tumor DNA using next-generation sequencing and ALK gene rearrangement by FFPE tumor tissue, and follow-up data regarding treatment modalities and outcomes were collected.

Results: The median age of the patients was 57 years (range: 32-79 years). Out of 131 patients, 97 were males (74%), and 90 (68.7%) were smokers. Among 128 patients tested, 16 (12.5%) had EGFR mutations detected with either technique by formalin-fixed paraffin-embedded (FFPE) tumor tissue or/and serum circulating tumor DNA using next-generation sequencing, and 6 (4.7%) had ALK rearrangement by FFPE tumor tissue. The majority (62.6%) presented with metastatic disease. Among the 102 patients who received first-line systemic therapy, the objective response rate was 50.0% in mutated NSCLC versus 14.6% in non-mutated (p < 0.001). Among the eight mutated patients who received first-line tyrosine kinase inhibitors (TKIs), 7 patients achieved either complete response or partial response. Among the 22 mutated patients, the median overall survival was 3 months in those who did not receive targeted therapy versus not reached in those who received any type of targeted therapy (p < 0.001).

Conclusion: Screening patients with newly diagnosed non-squamous NSCLC for driver mutations is essential for major prognostic and therapeutic implications. Early administration of TKIs in mutated patients significantly improves disease outcomes.

Background: We previously reported that in highly metastatic breast cancer cells, doxorubicin (DOX) at non-toxic concentrations promoted cell migration and invasion. Hesperidin (30, 5, 9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavonoid glycoside isolated from citrus/lemon plant that possesses a cytotoxic effect in several cancer cells. In this study, we investigate whether DOX efficacy is enhanced by hesperidin (Hsd) and the molecular pathway involved in highly metastatic breast cancer, 4T1.

Methods: Combined cytotoxicity of Hsd and DOX was evaluated with MTT assay and was analyzed using Chou-Talalay's method. To better understand the underlying mechanism, several factors, including apoptosis and cell cycle arrest were analyzed by flow cytometry. In addition, antimigration activity was evaluated by scratch wound healing assay, MMP-9 expression by ELISA and gelatin zymography, and Rac-1 protein level using western blot. The data on survival rate and expression level of MMP-9 and Rac-1 were obtained from Gene Expression OMNIBUS (GEO).

Results: Under MTT assay, Hsd showed a cytotoxic effect in a concentration-dependent manner with an IC50 value of 284 µM on 4T1 cells. Hsd synergistically enhanced the cytotoxic effect of DOX which seemed to correlate with an increase in apoptotic cell death, G2/M cell cycle arrest and blocked the migration of 4T1 cells. At 10 nM, doxorubicin induced lamellipodia formation, and increased the level of Rac-1 and metalloproteinase-9 (MMP-9) expression. Interestingly, combined treatment of DOX and Hsd dramatically downregulated the expression of MMP-9 and Rac-1. These results indicated that Hsd block the cell migration induced by DOX under in vitro studies.

Conclusion: These findings strongly suggest that Hsd possesses a potential synergistic effect that can be developed to enhance the anticancer efficacy of DOX and reduce the risks of chemotherapy use in highly metastatic breast cancer.