Advanced machine learning unveils CD8 + T cell genetic markers enhancing prognosis and immunotherapy efficacy in breast cancer.

BACKGROUND: Breast cancer (BC) is the most common cancer in women and poses a significant health burden, especially in China. Despite advances in diagnosis and treatment, patient variability and limited early detection contribute to poor outcomes. This study examines the role of CD8 + T cells in the tumor microenvironment to identify new biomarkers that improve prognosis and guide treatment strategies. METHODS: CD8 + T-cell marker genes were identified using single-cell RNA sequencing (scRNA-seq), and a CD8 + T cell-related gene prognostic signature (CTRGPS) was developed using 10 machine-learning algorithms. The model was validated across seven independent public datasets from the GEO database. Clinical features and previously published signatures were also analyzed for comparison. The clinical applications of CTRGPS in biological function, immune microenvironment, and drug selection were explored, and the role of hub genes in BC progression was further investigated. RESULTS: We identified 71 CD8 + T cell-related genes and developed the CTRGPS, which demonstrated significant prognostic value, with higher risk scores linked to poorer overall survival (OS). The model's accuracy and robustness were confirmed through Kaplan-Meier and ROC curve analyses across multiple datasets. CTRGPS outperformed existing prognostic signatures and served as an independent prognostic factor. The role of the hub gene TTK in promoting malignant proliferation and migration of BC cells was validated. CONCLUSION: The CTRGPS enhances early diagnosis and treatment precision in BC, improving clinical outcomes. TTK, a key gene in the signature, shows promise as a therapeutic target, supporting the CTRGPS's potential clinical utility.

Epitranscriptomic orchestrations: Unveiling the regulatory paradigm of m6A, A-to-I editing, and m5C in breast cancer via long noncoding RNAs and microRNAs.

Breast cancer (BC) poses a persistent global health challenge, particularly in countries with elevated human development indices linked to factors such as increased life expectancy, education, and wealth. Despite therapeutic progress, challenges persist, and the role of epitranscriptomic RNA modifications in BC remains inadequately understood. The epitranscriptome, comprising diverse posttranscriptional modifications on RNA molecules, holds the potential to intricately modulate RNA function and regulation, implicating dysregulation in various diseases, including BC. Noncoding RNAs (ncRNAs), acting as posttranscriptional regulators, influence physiological and pathological processes, including cancer. RNA modifications in long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) add an extra layer to gene expression control. This review delves into recent insights into epitranscriptomic RNA modifications, such as N-6-methyladenosine (m6A), adenine-to-inosine (A-to-I) editing, and 5-methylcytosine (m5C), specifically in the context of lncRNA and miRNAs in BC, highlighting their potential implications in BC development and progression. Understanding this intricate regulatory landscape is vital for deciphering the molecular mechanisms underlying BC and identifying potential therapeutic targets.

Specific cellular accumulation of photofrin-II in EC cells promotes photodynamic treatment efficacy in esophageal cancer.

Photodynamic therapy (PDT), which uses a light-sensitive compound and laser irradiation, is a light-based oncological treatment modality. PDT offers an alternative, less invasive treatment for various malignant tumors, such as esophageal cancer (EC), through a photochemical reaction induced by photofrin-II or other oncotropic photosensitizers without severe complications. Previous studies has shown that cancerous tissues accumulated more photosensitizers than paired normal tissues, however, whether it is cellular or vascular mechanisms remains unknown. Herein, in vivo and in vitro examinations were performed to study the mechanisms by which photofrin-II effectively and specifically killed EC cells. In this study, EC tissue of patients treated with photofrin-II, human ESCC cellline SHEEC and parental normal cellline SHEE, primary culture cells of EC tissue were used. The concentration of photofrin-II in cells were evaluated by high-performance liquid chromatography (HPLC). The results exhibited that accumulation of photofrin-II in cancerous cells were significantly higher than that in non-cancerous cells (p<0.05) under certain dose and time period of incubation of photofrin-II. In summary, our study showed that, photofrin-II specifically accumulated in EC cells in vivo and in vitro after controlling for vascular factors, which provided strong evidence that maybe the cellular factor is the main mechanism by which photofrin-II-mediated PDT selectively caused EC cells death.

Apoptotic effects of Photofrin-Diomed 630-PDT on SHEEC human esophageal squamous cancer cells.

Photodynamic therapy (PDT) using photofrin-II is a clinically effective treatment for both non-neoplastic and neoplastic diseases. Herein, we performed an in vitro experiment to study the anti-tumor effect and mechanisms of photofrin-II mediated PDT for esophageal squamous cell carcinoma (ESCC) cell line, SHEEC. In this study, human ESCC cell line SHEEC and parental normal cell line SHEE were used. The anti-tumor effect of PDT was determined by evaluating cell viability using CCK-8 assay, apoptosis and generation of reactive oxygen species (ROS). PDT induced significant apoptosis in SHEEC and SHEE cells in a time- and photofrin-II dose-dependent manner. Furthermore, PDT treatment induced significant death of SHEEC, instead of SHEE cells. The apoptotic outcome was accompanied by concurrent generation of ROS. In summary, PDT shed light on therapy of ESCC, functioning as a useful tool for ESCC clinical treatment, providing a better understanding of Photofrin-Diomed 630-PDT in SHEEC cells.

[Absorption and elimination of photofrin-II in human immortalization esophageal epithelial cell line SHEE and its malignant transformation cell line SHEEC].

BACKGROUND AND OBJECTIVE: The mechanism of tumor tissues selectively uptake the photosensitizer in photodynamic therapy (PDT) is still unclear. This study was to investigate the affinity of tumor cells to the photosensitizer photofrin-II. METHODS: Ultraviolet spectrophotometer was applied to measure the absorption spectra of various cell culture media. The fluorescence spectrum of photofrin-II was determined by spectrofluorometer. The absorption and elimination condition of photofrin-II were detected in immortalized human esophageal epithelial cell line SHEE and its malignant transformation cell line SHEEC. RESULTS: The maximum excitation wavelength of fluorescence for photofrin-II was (395.0+/-0.5) nm, and the maximum emission wavelength of that was (634.1+/-0.5) nm. The laser at the wavelength of 630 nm used in this experiment could permeate various types of cell culture media. There was no significant difference in the absorption and elimination of photofrin-II between SHEE and SHEEC at the same concentration and time. The absorption of photofrin-II in SHEE and SHEEC increased with the increase in photofrin-II concentration and duration, and reached the platform at the concentration of 30 microg/mL and a time point of 150 min, respectively. The photofrin-II contents of SHEE and SHEEC showed a slight change after 15-30 min, and diminished rapidly after 30 min. CONCLUSION: High photosensitizer concentration in tumor tissues may be not correlated with the affinity of tumor cells.

[Expression and clinical significance of KiSS-1 and E-cadherin in gastric cardia carcinoma].

OBJECTIVE: To investigate the expression and clinical significance of KiSS- 1 and E- cadherin in gastric cardia carcinoma and the correlation between the two proteins. METHODS: The expression of KiSS- 1 and E- cadherin in 80 patients with gastric cardia carcinoma and 20 patients with normal gastric cardia epithelium was detected by immunohistochemical technique. RESULTS: The expression of KiSS- 1 was negatively correlated with lymphatic metastasis and clinical stage (P < 0.05), but not correlated with the cancer differentiation (P < 0.05). The expression of E- cadherin was negatively correlated with lymphatic metastasis, clinical stage, and cancer differentiation (P < 0.05). Spearman test showed a positive correlation between KiSS- 1 and E- cadherin expression (r(s)=0.722, P < 0.05). CONCLUSION: KiSS- 1 and E- cadherin may play important roles in inhibiting the invasion and metastasis of gastric cardia carcinoma.