Search Results (143)

In RNA-seq data analysis, condensing the gene count matrix size is pivotal for downstream investigations, particularly pathway analysis. For this purpose, harnessing machine learning attracts increasing interest, while conventional methodologies depend on p-value comparisons. In this study, 20 tissue samples from real-world cervical cancers were subjected to sequencing, followed by the application of the Mclust algorithm to delineate an optimal cluster. By stratifying tumor budding into high and low groups and quantifying the epithelial-to-mesenchymal transition (EMT) score to scrutinize tumor budding, we discerned 24 EMT-related genes, with 5 showing strong associations with cervical cancer prognosis. Our observations elucidate a biological flow wherein EMT, Matrix Metallopep-tidase 2 (MMP2), and extracellular matrix (ECM) degradation are interconnected, ultimately leading to collagen type VI and exacerbating the prognosis of cervical cancer. The present study underscores an alternative method for selecting useful EMT-related genes by employing an appropriate clustering algorithm, thereby avoiding classical methods while unveiling novel insights into cervical cancer etiology and prognosis. Moreover, when comparing high and low tumor budding, collagen type VI emerges as a potential gene marker for the prognosis of cervical cancer. Full article

Colorectal cancer (CRC) is a frequent, worldwide tumor described for its huge complexity, including inter-/intra-heterogeneity and tumor microenvironment (TME) variability. Intra-tumor heterogeneity and its connections with metabolic reprogramming and epithelial–mesenchymal transition (EMT) were investigated with explorative shotgun proteomics complemented by a Random Forest (RF) machine-learning approach. Deep and superficial tumor regions and distant-site non-tumor samples from the same patients (n = 16) were analyzed. Among the 2009 proteins analyzed, 91 proteins, including 23 novel potential CRC hallmarks, showed significant quantitative changes. In addition, a 98.4% accurate classification of the three analyzed tissues was obtained by RF using a set of 21 proteins. Subunit E1 of 2-oxoglutarate dehydrogenase (OGDH-E1) was the best classifying factor for the superficial tumor region, while sorting nexin-18 and coatomer-beta protein (beta-COP), implicated in protein trafficking, classified the deep region. Down- and up-regulations of metabolic checkpoints involved different proteins in superficial and deep tumors. Analogously to immune checkpoints affecting the TME, cytoskeleton and extracellular matrix (ECM) dynamics were crucial for EMT. Galectin-3, basigin, S100A9, and fibronectin involved in TME–CRC–ECM crosstalk were found to be differently variated in both tumor regions. Different metabolic strategies appeared to be adopted by the two CRC regions to uncouple the Krebs cycle and cytosolic glucose metabolism, promote lipogenesis, promote amino acid synthesis, down-regulate bioenergetics in mitochondria, and up-regulate oxidative stress. Finally, correlations with the Dukes stage and budding supported the finding of novel potential CRC hallmarks and therapeutic targets. Full article

Breast cancer has the highest diagnosis rate among all cancers. Tumor budding (TB) is recognized as a recent prognostic marker. Identifying genes specific to high-TB samples is crucial for hindering tumor progression and metastasis. In this study, we utilized an RNA sequencing technique, called TempO-Seq, to profile transcriptomic data from breast cancer samples, aiming to identify biomarkers for high-TB cases. Through differential expression analysis and mutual information, we identified seven genes (NOL4, STAR, C8G, NEIL1, SLC46A3, FRMD6, and SCARF2) that are potential biomarkers in breast cancer. To gain more relevant proteins, further investigation based on a protein–protein interaction network and the network diffusion technique revealed enrichment in the Hippo signaling and Wnt signaling pathways, promoting tumor initiation, invasion, and metastasis in several cancer types. In conclusion, these novel genes, recognized as overexpressed in high-TB samples, along with their associated pathways, offer promising therapeutic targets, thus advancing treatment and diagnosis for breast cancer. Full article

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial–mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. This study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had significantly higher Mucin-1 (p < 0.001) and cytoplasmic E-cadherin (p = 0.043) scores; they were significantly less differentiated (p = 0.007), more advanced (p = 0.027), and predominately affected right the colon (p = 0.039) compared to non-mucinous tumors. Epithelial tumors were significantly better differentiated (p = 0.034) and with less prominent tumor budding (p < 0.001) than mesenchymal tumors. Mucin-1 and Vimentin were independent predictors of tumor differentiation (p = 0.006) and budding (p = 0.001), respectively. Mucinous histology and EMT markers are significant predictors of disease severity and tumor characteristics in early-onset colorectal cancer. Full article

The chemical composition of extracts (CEs) and essential oils (EOs) from Tetradenia riparia leaves, flower buds, and stems was analyzed. Antiproliferative activity against tumor cell lines, NO production inhibition, and antioxidant and antiviral activities were assessed. The CEs contained flavonoids, phenolic acids, coumarins, and saturated fatty acids. The EOs included monoterpenes, oxygenated sesquiterpenes, and diterpenes. NO production inhibition ranged from 76 to 247 µg mL⁻¹, and antiproliferative activity exhibited GI₅₀ between 20 and >204 µg mL⁻¹, with low cytotoxicity (SI: 1.08 to 4.75). Reactive oxygen species inhibition ranged from 45 to 82%. Antioxidant activity varied when determined by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay (IC₅₀: 0.51 to 8.47 mg mL⁻¹) and ferric reducing antioxidant power (0.35 to 0.81 µM ferrous sulfate per mg). The reduction in β-carotene–linoleic acid co-oxidation varied between 76.13 and 102.25%. The total phenolic content of CEs and EOs was 10.70 to 111.68 µg gallic acid mg⁻¹. Antiviral activity against herpes simplex virus type 1 (HSV-1) showed an EC₅₀ between 9.64 and 24.55 µg mL⁻¹ and an SI between 8.67 and 15.04. Leaf EOs exhibited an EC₅₀ of 9.64 µg mL⁻¹ and an SI of 15.04. Our study unveils the diverse chemical composition and multifaceted pharmacological properties of T. riparia, demonstrating its potential as a valuable source of bioactive compounds for therapeutic applications. Full article

(1) Background: Colorectal cancer (CRC) remains a significant cause of morbidity and mortality worldwide, with its prognosis influenced by genetic and clinicopathological factors. This study investigates the associations between the gene expressions of Arylsulfatase B (ARSB), TP53, and Maspin, alongside traditional clinicopathological features, and their impact on CRC survival outcomes. (2) Methods: 70 consecutive CRC cases were analyzed for ARSB, TP53, and Maspin gene expression using RT-qPCR, and their protein levels were assessed through immunohistochemistry. Clinicopathological parameters—age, gender, tumor localization, macroscopic and microscopic aspects, lymph node ratio, pT stage, and tumor budding—were evaluated for their prognostic significance. Kaplan–Meier survival analysis with Cox proportional hazards regression was used to determine their impact on overall survival. (3) Results: No significant survival differences were observed based on age, gender, tumor localization, and macroscopic aspect. The microscopic aspect and pT stage showed significant associations with survival, with poorer outcomes in G3 and pT3/pT4 stages, respectively. Immunohistochemical positivity for ARSB and Maspin indicated a longer survival, while TP53 protein expression alone did not significantly impact the prognosis. Dual high gene expression (ARSB + TP53, TP53 + Maspin) and triple high gene expression (ARSB + TP53 + Maspin) were significantly associated with better survival outcomes. (4) Conclusions: The combined gene expression profile of ARSB, TP53, and Maspin presents a novel prognostic marker in CRC, offering insights into the molecular dynamics of cancer cells and potential therapeutic targets. These findings emphasize the importance of integrating molecular markers with traditional clinicopathological factors for a more accurate prognostication and personalized treatment approach in CRC. Full article

Background: The low positive predictive value for lymph node metastases (LNM) of common practice risk criteria (CPRC) in T1 colorectal carcinoma (CRC) leads to manyunnecessary additional surgeries following local resection. This study aimed to identify criteria that may improve on the CPRC. Methods: Logistic regression analysis was performed to determine the association of diverse variables with LNM or ‘poor outcome’ (LNM and/or distant metastases and/or recurrence) in a single center T1 CRC cohort. The diagnostic capacity of the set of variables obtained was compared with that of the CPRC. Results: The study comprised 161 cases. Poorly differentiated clusters (PDC) and tumor budding grade > 1 (TB > 1) were the only independent variables associated with LNM. The area under the curve (AUC) for these criteria was 0.808 (CI 95% 0.717–0.880) compared to 0.582 (CI 95% 0.479–0.680) for CPRC. TB > 1 and lymphovascular invasion (LVI) were independently associated with ‘poor outcome’, with an AUC of 0.801 (CI 95% 0.731–0.859), while the AUC for CPRC was 0.691 (CI 95% 0.603–0.752). TB > 1, combined either with PDC or LVI, would reduce false positives between 41.5% and 45% without significantly increasing false negatives. Conclusions: Indicating additional surgery in T1 CRC only when either TB > 1, PDC, or LVI are present could reduce unnecessary surgeries significantly. Full article

As one of the most prevalent forms of cancer worldwide, breast cancer has garnered significant attention within the clinical research setting. While traditional treatment employs a multidisciplinary approach including a variety of therapies such as chemotherapy, hormone therapy, and even surgery, researchers have since directed their attention to the budding role of neoantigens. Neoantigens are defined as tumor-specific antigens that result from a multitude of genetic alterations, the most prevalent of which is the single nucleotide variant. As a result of their foreign nature, neoantigens elicit immune responses upon presentation by Major Histocompatibility Complexes I and II followed by recognition by T cell receptors. Previously, researchers have been able to utilize these immunogenic properties and manufacture neoantigen-specific T-cells and neoantigen vaccines. Within the context of breast cancer, biomarkers such as tumor protein 53 (TP53), Survivin, Partner and Localizer of BRCA2 (PALB2), and protein tyrosine phosphatase receptor T (PTPRT) display exceeding potential to serve as neoantigens. However, despite their seemingly limitless potential, neoantigens must overcome various obstacles if they are to be fairly distributed to patients. For instance, a prolonged period between the identification of a neoantigen and the dispersal of treatment poses a serious risk within the context of breast cancer. Regardless of these current obstacles, it appears highly promising that future research into neoantigens will make an everlasting impact on the health outcomes within the realm of breast cancer. The purpose of this literature review is to comprehensively discuss the etiology of various forms of breast cancer and current treatment modalities followed by the significance of neoantigens in cancer therapeutics and their application to breast cancer. Further, we have discussed the limitations, future directions, and the role of transcriptomics in neoantigen identification and personalized medicine. The concepts discussed in the original and review articles were included in this review article. Full article

Sinonasal intestinal-type adenocarcinoma (ITAC) is a very rare, closely occupational-related tumor with strong histological similarities to colorectal cancer (CRC). In the latter, tumor budding (TB) is widely recognized as a negative prognostic parameter. The aim of this study was to evaluate the prognostic role of TB in ITAC and to correlate it with other established or emerging biomarkers of the disease, such as p53 and deficient DNA mismatch repair (MMR) system status/microsatellite instability (MSI). We retrospectively analyzed 32 consecutive specimens of patients with ITAC diagnosis treated in two institutions in Northern Italy. We reviewed surgical specimens for TB evaluation (low-intermediate/high); p53 expression and MMR proteins were evaluated via immunohistochemistry. Results were retrospectively stratified using clinical data and patients’ outcomes. According to bud counts, patients were stratified into two groups: intermediate/high budding (>4 TB) and low budding (≤4 TB). Patients with high TB (>4) have an increased risk of recurrence and death compared to those with low TB, with a median survival of 13 and 54 months, respectively. On multivariate analysis, considering TB, therapy, and stage as covariates, TB emerged as an independent prognostic factor net of the stage of disease or type of therapy received. No impact of p53 status as a biomarker of prognosis was observed and no alterations regarding MMR proteins were identified. The results of the present work provide further significant evidence on the prognostic role of TB in ITAC and underline the need for larger multicenter studies to implement the use of TB in clinical practice. Full article

Encoded by the CDX2 homeobox gene, the CDX2 protein assumes the role of a pivotal transcription factor localized within the nucleus of intestinal epithelial cells, orchestrating the delicate equilibrium of intestinal physiology while intricately guiding the precise development and differentiation of epithelial tissue. Emerging research has unveiled that positive immunohistochemical expression of this protein shows that the CDX2 gene exerts a potent suppressive impact on tumor advancement in colorectal cancer, impeding the proliferation and distant dissemination of tumor cells, while the inhibition or suppression of CDX2 frequently correlates with aggressive behavior in colorectal cancer. In this study, we conducted an immunohistochemical assessment of CDX2 expression on a cohort of 43 intraoperatively obtained tumor specimens from patients diagnosed with colon cancer at Colțea Clinical Hospital in Bucharest, between April 2019 and December 2023. Additionally, we shed light on the morphological diversity within colon tumors, uncovering varying differentiation grades within the same tumor, reflecting the variations in CDX2 expression as well as the genetic complexity underlying these tumors. Based on the findings, we developed an innovative immunohistochemical scoring system that addresses the heterogeneous nature of colon tumors. Comprehensive statistical analysis of CDX2 immunohistochemical expression unveiled significant correlations with known histopathological parameters such as tumor differentiation grades (p-value = 0.011) and tumor budding score (p-value = 0.002), providing intriguing insights into the complex involvement of the CDX2 gene in orchestrating tumor progression through modulation of differentiation processes, and highlighting its role in metastatic predisposition. The compelling correlation identified between CDX2 expression and conventional histopathological parameters emphasizes the prognostic significance of the CDX2 biomarker in colon cancer. Moreover, our novel immunohistochemical scoring system reveals a distinct subset of colon tumors exhibiting reserved prognostic outcomes, distinguished by their “mosaic” CDX2 expression pattern. Full article

Background/Objectives: Recently, some new morphological features of colorectal cancer have been discovered as important prognostic factors; in this paper, we study the relationship between tumor budding (TB) and tumor deposits (TDs). Methods: The retrospective cohort study included 90 patients with pathohistologically confirmed stage III CRC who were treated with radical surgical resection. All hematoxylin and eosin (H and E)-stained slides from each patient were reviewed, and histological parameters were recorded. The samples were divided into two groups with similar sizes: a group without TDs (N = 51) and a control group with TDs (N = 39). The presence and TB grade were further analyzed in these groups and compared with other clinical and histological features. Results: The prevalence of TB in the investigated cohort was unexpectedly high (94.4%). Overall, there were 23 (25.6%) Bd1, 20 (22.2%) Bd2, and 47 (52.2%) Bd3 cases. The presence of TDs was significantly associated with a higher number of TB (p < 0.001, OR 16.3) and, consequently, with a higher TB grade (p = 0.004, OR 11.04). A higher TB grade (p = 0.001, HR 2.28; 95% CI 1.93–4.76) and a growing number of TDs (p = 0.014, HR 1.52; 95% CI 1.09–2.1) were statistically significantly associated with shorter survival. Conclusions: TDs appear more often in patients with higher TB grades in stage III CRC. A higher TB grade and a growing number of TDs were statistically significantly associated with shorter overall survival. These results could give additional emphasis to the importance of TB as an adverse prognostic factor since a strong relationship with TDs has been demonstrated. Full article

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. The incidence of metastasis for cSCC is estimated to be around 1.2–5%. Ribosomal protein S6 (p-S6) and the p21 protein (p21) are two proteins that play central roles in other cancers. These proteins may be equally important in cSCC, and together, these could constitute a good candidate for metastasis risk assessment of these patients. We investigate the relationship of p-S6 and p21 expression with the impact on the prognosis of head and neck cSCC (cSCCHN). p-S6 and p21 expression was analyzed by immunohistochemistry on paraffin-embedded tissue samples from 116 patients with cSCCHN and associations sought with clinical characteristics. Kaplan–Meier estimators and Cox proportional hazard regression models were also used. The expression of p-S6 was significantly inversely associated with tumor thickness, tumor size, desmoplastic growth, pathological stage, perineural invasion and tumor buds. p21 expression was significantly inversely correlated with >6 mm tumor thickness, desmoplastic growth, and perineural invasion. p-S6-negative expression significantly predicted an increased risk of nodal metastasis (HR = 2.63, 95% CI 1.51–4.54; p < 0.001). p21 expression was not found to be a significant risk factor for nodal metastasis. These findings demonstrate that p-S6-negative expression is an independent predictor of nodal metastasis. The immunohistochemical expression of p-S6 might aid in better risk stratification and management of patients with cSCCHN. Full article

Background: Early-stage tongue cancer has a good prognosis in general; however, high-risk patients with late cervical lymph node and distant metastases have a poor prognosis. Elective neck dissection and postoperative chemoradiotherapy are considered for these patients, although no clear criteria have been identified for their evaluation. Methods: This retrospective observational study aimed to determine the predictive factors for late cervical lymph node and distant metastases in 102 patients with cT1-2N0 tongue cancer. The data regarding the demographic characteristics, as well as the depth of invasion, tumor budding, histological grade, and tumor–stromal ratio, among other things, were extracted from medical records. Results: We found that the potential lymph node metastasis rate was 27.5%. The significant clinical predictors of late cervical lymph node metastasis were the tumor thickness and endophytic growth pattern and the significant histopathological factors were poorly and moderately differentiated tumors and ≥3 tumor buds. In addition, the prognostic factors for distant metastasis included ≥4 lymph node metastases, ≥7 tumor budding, and moderate and poor tumor differentiation. Conclusions: The usefulness of tumor budding as a predictor of metastasis for tongue cancer was suggested. The findings of this study can help establish the criteria for evaluating the metastasis risk and prognosis of patients with tongue cancers. Full article

Background: Tumor budding (TB) is a histomorphological characteristic of the tumor invasion front and it has an impact on the tumor outcome prediction for head and neck squamous cell carcinoma (HNSCC) aetiopathology. Patients and methods: The average TB score (TB rel) of all tumor-positive marginal sections (n = 443) in the primary tumor was analyzed in the FFPE-fixed tumor slices of 66 patients with HNSCC, and they were compared with cryo-fixed sections. Results: TB rel correlates with tumor aggressiveness (i.e., lymph node metastasis quantity, lymph node ratio, extra capsular growth, Pn1, pV1, grading). The TB scores often vary between the different tumor margins of FFPE sections in the same patient, and in many cases, they differ depending on the fixation method. Conclusion: Our data show that a randomly selected marginal cut cannot reliably mirror the TB score, and thus, they cannot predict the prognostic outcome. However, TB rel could be a tool that compensates for differences in TB score analysis. TB score determination in cryo sections seems to be inaccurate compared with TB determination in FFPE. Full article