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Spectral Clustering is a graph clustering algorithm that makes use of eigenvector obtained from a matrix describing pairwise similarity between data points. It provides a dimensionality reduction for clustering in lower dimensions. One example of spectral clustering application is the clustering of protein-protein interaction (PPI) network. PPI networks are usually represented as a graph network with proteins and interactions as vertices and edges respectively. However, this spectral clustering only produces a hard clustering of proteins, whereas there may be some relationship between each protein clusters, and possibly multiple functionality for each proteins that has not been detected before. Fuzzy Random Walk is a fuzzy clustering method based on transition probability from a random walk on a dataset. In this paper, we combine both Spectral Clustering and Fuzzy Random Walk to cluster PPI network of protein TP53, a protein thatplays an important role in managing cell cycle, especially in tumor cell suppression. Using PPI dataset of TP53 obtained from the STRING database, we found the combined algorithm is proven to produce both robust and fuzzy clusters with each cluster explains one of TP53 protein's functionality related to the tumor cell.

P53 overexpression plays a critical role in cancer pathogenesis by disrupting the intricate regulation of cellular proliferation. Despite its firmly established function as a tumor suppressor, elevated p53 levels can paradoxically contribute to tumorigenesis, influenced by factors such as exposure to carcinogens, genetic mutations, and viral infections. This phenomenon is observed across a spectrum of cancer types, including bladder (BLCA), ovarian (OV), cervical (CESC), cholangiocarcinoma (CHOL), colon adenocarcinoma (COAD), diffuse large B-cell lymphoma (DLBC), esophageal carcinoma (ESCA), head and neck squamous cell carcinoma (HNSC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). This broad spectrum of cancers is often associated with increased aggressiveness and recurrence risk. Effective therapeutic strategies targeting tumors with p53 overexpression require a comprehensive approach, integrating targeted interventions aimed at the p53 gene with conventional modalities such as chemotherapy, radiation therapy, and targeted drugs. In this extensive study, we present a detailed analysis shedding light on the multifaceted role of TP53 across various cancers, with a specific emphasis on its impact on disease-free survival (DFS). Leveraging data from the TCGA database and the GTEx dataset, along with GEPIA, UALCAN, and STRING, we identify TP53 overexpression as a significant prognostic indicator, notably pronounced in prostate adenocarcinoma (PRAD). Supported by compelling statistical significance (p < 0.05), our analysis reveals the distinct influence of TP53 overexpression on DFS outcomes in PRAD. Additionally, graphical representations of overall survival (OS) underscore the notable disparity in OS duration between tumors exhibiting elevated TP53 expression (depicted by the red line) and those with lower TP53 levels (indicated by the blue line). The hazard ratio (HR) further emphasizes the profound impact of TP53 on overall survival. Moreover, our investigation delves into the intricate TP53 protein network, unveiling genes exhibiting robust positive correlations with TP53 expression across 13 out of 27 cancers. Remarkably, negative correlations emerge with pivotal tumor suppressor genes. This network analysis elucidates critical proteins, including SIRT1, CBP, p300, ATM, DAXX, HSP 90-alpha, Mdm2, RPA70, 14-3-3 protein sigma, p53, and ASPP2, pivotal in regulating cell cycle dynamics, DNA damage response, and transcriptional regulation. Our study underscores the paramount importance of deciphering TP53 dynamics in cancer, providing invaluable insights into tumor behavior, disease-free survival, and potential therapeutic avenues.

Introduction: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Methods: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Results and conclusion: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers’ expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

A series of benzimidazole-derived chalcones containing aromatic amide substituent were designed and synthesized. All of the chalcone compounds were tested for their in vitro antitumor activity against human cancer cell lines (HCT116, HepG2, A549, and CRL-5908). The antiproliferative activity of compounds 3, 6, 9, 14, 15, 16 against HCT116 cells was significantly better than that that of 5-Fluorouracil (IC50: 94.63 µM). The antitumor activity of these compounds showed obvious differences between the wild type HCT116 and mutant HCT116 (TP53−/−) cells. A preliminary mechanistic study suggested that these compounds act by upregulating the expression of TP53 protein in tumor cells without inhibiting the MDM2-TP53 interaction.

Non-Small-Cell Lung Cancer (NSCLC) is the primary cause of cancer-related death worldwide. Oncogene-addicted patients usually benefit from targeted therapy, but primary and acquired resistance mechanisms inevitably occur. Tumor protein 53 (TP53) gene is the most frequently mutated gene in cancer, including NSCLC. TP53 mutations are able to induce carcinogenesis, tumor development and resistance to therapy, influencing patient prognosis and responsiveness to therapy. TP53 mutants present in different forms, suggesting that different gene alterations confer specific acquired protein functions. In recent years, many associations between different TP53 mutations and responses to Epidermal Growth Factor Receptor (EGFR) targeted therapy in NSCLC patients have been found. In this review, we discuss the current landscape concerning the role of TP53 mutants to guide primary and acquired resistance to Tyrosine-Kinase Inhibitors (TKIs) EGFR-directed, investigating the possible mechanisms of TP53 mutants within the cellular compartments. We also discuss the role of the TP53 mutations in predicting the response to targeted therapy with EGFR-TKIs, as a possible biomarker to guide patient stratification for treatment.

In the present study, we analyzed the proliferation and apoptosis of trophoblasts and human decidual cells in patients with recurrent spontaneous abortion and the related cellular pathway mechanism. Thirty-four patients with recurrent abortion and 30 healthy pregnant women undergoing planned artificial abortion were selected. The trophoblast and decidual cells were collected by negative pressure aspiration technique. TUNEL method was used to detect the apoptosis rate. Immunohistochemical method was used for detection of TP53 protein. Quantitative real-time PCR was used for detection of the relative expression level of CDKN1A and Bax mRNA. It was found that the cell apoptosis rate in the recurrent miscarriage group was significantly increased and the expression levels of TP53 protein, CDKN1A and Bax mRNA were also significantly increased (p<0.05). In conclusion, the trophoblast and decidual cells of patients with recurrent abortion were obviously apoptotic, which was probably related to abnormal expression of the CDKN1A and Bax genes mediated by TP53 protein through cellular pathways.

The EP300 protein is a histone acetyltransferase 1 , 2 that regulates transcription via chromatin remodelling 3 and is important in the processes of cell proliferation 4 and differentiation 5 . EP300 acetylation of TP53 in response to DNA damage regulates its DNA-binding and transcription functions 6 , 7 , 8 , 9 . A role for EP300 in cancer has been implied by the fact that it is targeted by viral oncoproteins, it is fused to MLL in leukaemia and two missense sequence alterations in EP300 were identified in epithelial malignancies 10 , 11 , 12 , 13 . Nevertheless, direct demonstration of the role of EP300 in tumorigenesis by inactivating mutations in human cancers has been lacking. Here we describe EP300 mutations, which predict a truncated protein, in 6 (3%) of 193 epithelial cancers analysed. Of these six mutations, two were in primary tumours (a colorectal cancer and a breast cancer) and four were in cancer cell lines (colorectal, breast and pancreatic). In addition, we identified a somatic in-frame insertion in a primary breast cancer and missense alterations in a primary colorectal cancer and two cell lines (breast and pancreatic). Inactivation of the second allele was demonstrated in five of six cases with truncating mutations and in two other cases. Our data show that EP300 is mutated in epithelial cancers and provide the first evidence that it behaves as a classical tumour-suppressor gene.

Tumor suppressor protein, TP53 also known as the “guardian of the genome” plays a key role in preventing malignant transformation. Almost 50% of human tumors carry mutations in this gene; in the remaining tumors, the TP53 network is functionally inoperative. The majority of TP53 mutations are missense mutations and more than 90% of the missense mutations affect specific codons in the DNA-binding domain, called “hotspot codons.” The present study was aimed at analyzing the germline mutation status of four hotspot codons in TP53 namely, codon 175, codon 245, codon 248 (within the DNA binding domain) and codon 72 (outside the DNA binding domain) in cancer cases encountered in a tertiary care hospital in South India by PCR-RFLP. The case-control study included 85–10 subjects respectively. The results of the study indicated that majority of the cancer cases did not harbor germline mutations in the four hot spot codons of TP53. The study further highlights the usefulness of PCR-RFLP as a simple and cost effective tool for checking gene mutations.

About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). The persistence of the infection is controlled by several mechanisms including the induction of oxidative stress. HCV relies on this strategy to redirect lipid metabolism machinery and escape immune response. The 3β-hydroxysterol Δ24-reductase (DHCR24) is one of the newly discovered host markers of oxidative stress. This protein, as HCV-induced oxidative stress responsive protein, may play a critical role in the pathogenesis of HCV chronic infection and associated liver diseases, when aberrantly expressed. The sustained expression of DHCR24 in response to HCV-induced oxidative stress results in suppression of nuclear p53 activity by blocking its acetylation and increasing its interaction with MDM2 in the cytoplasm leading to its degradation, which may induce hepatocarcinogenesis.