Cancer Management and Research最新文献

Purpose: The aim of this study was to explore the immune subtypes of endometrial cancer (EC) and its characteristics by immunogenes from the perspective of multidimensional genomics (multi-omics).

Patients and methods: Immune subtypes were carried out using an unsupervised non-negative matrix factorization clustering (NMF) method and their characteristics were analysed. Key genes were identified using random forest analysis. A predictive model for immune subtypes and their clinical prognosis were constructed. The relationship between immune subtypes and molecular subtypes was investigated.

Results: Two immune subtypes C1 and C2 were available. C2 patients were younger, less graded, had significantly higher immune cell infiltration, immune checkpoint expression, tumor neoantigens, tumor mutation load than C1 (P<005). S100A9, CD3D, CD3E, HLA-DRB1 and IL2RB were the key genes with significant survival outcomes. S100A9 expression was lower in C2 than C1, and IL2RB, HLA-DRB1, CD3E and CD3D expression was higher than C1 (P<0.05). The predictive accuracy of five key genes for immune subtypes was good, with a Receiver operating characteristic of 0.941. The incidence of TP53abn type in C2 was significantly lower than that of C1, and the incidence of POLE type was significantly higher than that of C1 (P<0.0001).

Conclusion: EC can be divided into two immune subtypes based on immunogenes. Low expression of S100A9 and high expression of IL2RB, HLA-DRB1, CD3E, and CD3D suggest sensitivity to immunotherapy and a good prognosis.

Introduction: Incidental Enhancement Lesions (IELs) complicate patient management but may be detected through multiparameter MRI including dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and synthetic magnetic resonance imaging (syMRI). The multiparameter MRI model gave greater objectivity to avoid unnecessary biopsy.

Case presentation: A 60 year-old woman had a history of occasional right breast pain and a mass was identified in the right breast. A thickening in the upper quadrant of the right outer breast was found during physical examination but no mass was palpable. Breast dynamic contrast enhancement MRI and synthetic MRI were performed prior to ultrasound-guided biopsy of the right breast lesion. Resection of the right breast lesion and sentinel lymph node was performed 2 days later. Chronic inflammation, locally invasive ductal carcinoma and high-grade ductal carcinoma in situ were found by pathological examination.

Discussion: Differentiation between benign and malignant breast IELs was facilitated by use of a multiparameter MRI model with DCE-MRI and syMRI, giving greater objectivity in differentiating between benign and malignant lesions.

Background: Prostate cancer (PCa) is not well understood because of its enormous biological heterogeneity and unreliable progression. We conducted this retrospective analysis to examine the variables predicting early and late progression to castration-resistant PCa (CRPC) for better management of this disease.

Methods: This single institutional retrospective study was conducted from January 2018 to January 2022. A total of 98 consecutive men meeting with the diagnosis of CRPC as per the inclusion criteria were included in the study and were stratified in four quartiles on the basis of time to CRPC (time to castration resistance [TTCR]) development. Early CRPC (1^st quartile, TTCR = 6-12 months) and late CRPC (4^th quartile, TTCR = 38-120 months) were then compared on the basis of different clinical, pathological and AR-LBD sequence to find the correlation with response duration.

Results: Median time to develop castration resistance was 25 ± 26.44 months. The mean age of the patients was 66.8 ± 9.20 years and median baseline PSA was calculated 100±685.06 ng/mL respectively. Higher Gleason score (≥7-10) was found to be significantly associated with early development of CRPC (p<0.001) and lower nadir PSA was significantly indicating late CRPC progression (p<0.005). No mutations were found in androgen receptor exon-5, 6, 7 except a homozygous mutation in the 7^th intronic region, which is involved in splice variants formation playing noteworthy role in CRPC development.

Conclusion: Time for metastatic PCa to CRPC ranges from 6-120 months revealing its heterogeneous nature. Early age presentation in the clinic and high initial PSA and high grade (GS>7) at diagnosis were positively associated with early CRPC while lower nadir PSA was correlated with late CRPC progression. No remarkable genomic mutations were discovered. Therefore, more data are needed and further research is required with large no. of patients to discover the predictive prognostic biomarkers for better patients' management.

Introduction: Breast cancer is highly metastatic. One protein that may participate in breast cancer cell migration is the actin motor protein myosin 6 (MYO6), which is likely regulated by the GIPC1 protein. Additionally, septins (SEPTs) appear to participate in breast cancer motility. Here, we investigated the effects of loss of MYO6 on cell morphology, migration, and expression of GIPC1, SEPT2, and SEPT7 in two breast cancer cell lines.

Material and methods: The research material consisted of two breast cancer cell lines, MCF-7 and MDA-MB-231, in which the level of MYO6 was reduced and the effect of knockdown on the migration potential and the expression of GIPC1, SEPT2 and SEPT7 was determined. The levels of these proteins were also analyzed in silico.

Results: siRNA-mediated knock down of MYO6 altered the morphology of MCF-7 cells and reduced the expression of GIPC1 and SEPT7 in both MCF-7 and MDA-MB-231 cells. In in silico data, GIPC1, SEPT2, and SEPT7 were all overexpressed in breast cancer tissue samples from patients. Finally, MYO6 knock down impaired migration and adhesion in both MCF-7 and MDA-MB-231 cells.

Conclusion: Our study substantiates that downregulation of MYO6 diminishes the migratory abilities of breast cancer cell lines with varying invasiveness. Furthermore, we have demonstrated that decreased MYO6 protein leads to reduced expression of GIPC1, SEPT2, and SEPT7 in breast cancer cells. These findings contribute to a more comprehensive understanding of the pathways influencing breast cancer cell migration, a critical aspect of metastasis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transformation (EMT), invasion, metastasis, metabolism, and drug resistance are the main factors affecting the development and treatment of tumors. MiRNAs play crucial roles in almost all major cellular biological processes. Studies have been carried out on miRNAs as biomarkers and therapeutic targets. Their dysregulation contributes to the progression and prognosis of HCC. This review aims to explore the molecular cascades and corresponding phenotypic changes caused by aberrant miRNA expression and their regulatory mechanisms, summarize and analyze novel biomarkers from somatic fluids (plasma/serum/urine), and highlight the latent capacity of miRNAs as therapeutic targets.

Introduction: Gastric cancer, the fifth most common malignant tumor in the world, poses a serious threat to human health. However, the role of fatty acid metabolism (FAM) in gastric cancer remains incompletely understood. We aim to provide guidance for clinical decisions by utilizing public database of gastric adenocarcinoma to establish an FAM-related gene subtypes via machine learning algorithm.

Methods: The intersection of FMGs from KEGG, Hallmark, and Reactome bioinformatics databases and the DEGs of the TCGA-STAD cohort was used to decompose the gene matrix related to establish FAM-related gene subtypes by NMF. Comparison of immune infiltrating differences between subtypes using ESTIMATE and Cibersort algorithms. The multifactor Cox regression to identify independent risk genes for patient prognosis based on the subtypes. A prognostic model including independent risk genes was built using random survival forest and Cox regression. IHC validation in gastric cancer and adjacent tissues confirmed the above gene expression level.

Results: 71 DEGs related to FMGs of STAD were identified, which was used to established the FAM-related gene subtypes, C1 and C2. The immune infiltrating analysis showed that most immune features of C2 were significantly upregulated compared to C1. The independent risk genes were CGβ8, UPK1B, and OR51G based on the subtypes. A gastric cancer prognostic model consisting of independent risk genes was constructed and patients were classified into high-risk and low-risk groups with survival differential analysis. Finally, IHC showed that CGβ8 and UPK1B expression were upregulated in gastric cancer, while OR51G2 did not detect differences in expression.

Conclusion: The study developed a machine learning-based gastric cancer prognosis risk model using FMGs. This model effectively stratifies patients according to their risk levels and provides valuable insights for clinical decision-making, enabling accurate evaluation of patient prognosis.

Background: The research on lymph node metastasis (LNM) in locally advanced gastric cancer (LAGC) infiltrating the subserous tissue and serous membrane (T3-4a) is significantly inadequate. This study aims to explore the clinicopathological factors related to LNM in stages T3 and T4a LAGC, while also developing predictive nomograms.

Methods: After systematic searching and rigorous screening, 1995 T3 and 1244 T4a LAGC cases who underwent surgery without neoadjuvant or perioperative chemotherapy were selected. The risk factors associated with LNM were identified using both univariate and multivariate logistic regression analyses. Subsequently, the independent variables identified through the multivariate analyses were utilized to construct a nomogram.

Results: The incidence of LNM in T3 and T4a LAGC was 77.1% (1539/1995) and 83.8% (1043/1244), respectively. The following factors were found to be independently associated with LNM in T3 LAGC: preoperative serum albumin <41g/L (P=0.007), gastrointestinal obstruction (P<0.001), tumor location (P=0.040), tumor size >4cm (P=0.002), mixed (P=0.001) and undifferentiated histological types (P=0.002), presence of lymphovascular invasion (LVI) (P<0.001) and nerve invasion (P<0.001). Additionally, in T4a LAGC cases, serum albumin < 39g/L (P=0.004), tumor size >6cm (P=0.020), mixed (P<0.001) and undifferentiated histological types (P<0.001), presence of gastrointestinal hemorrhage (P=0.016), neuroendocrine differentiation (P=0.024), and LVI (P<0.001) independently influenced the occurrence of LNM.

Conclusion: This study identified the risk factors associated with LNM in T3-4a LAGC cases and constructed nomograms, thereby providing valuable guidance for formulating and implementing a multidisciplinary perioperative treatment program.

Objective: To investigate the therapeutic efficacy of totally laparoscopic total gastrectomy (TLTG) versus laparoscopy-assisted total gastrectomy (LATG) in gastric cancer (GC) treatment, as well as their effects on postoperative inflammation and glucose and lipid metabolic status.

Methods: Clinical data of 68 individuals with GC who underwent LATG (n=31) and TLTG (n=37) from January 2020 to December 2022 were procured. This included intraoperative blood loss, operative time, incision length, number of lymph nodes dissected, postoperative complication rates, and recovery indicators, such as inflammation, glucose metabolism, and lipid metabolism.

Results: The TLTG cohort demonstrated significant advantages in intraoperative blood loss, operative time, and incision length compared to the LATG cohort. Furthermore, TLTG was superior in reducing the incidence of complications. Nevertheless, no substantial variation was observed in the quantity of lymph nodes dissected. Additionally, TLTG showed benefits in postoperative recovery, including better control of the inflammatory response, reduction of complication risks, shorter hospital stay, and alleviation of postoperative pain. TLTG also exhibited a reduced impact on inflammation and demonstrated greater effectiveness in improving postoperative glucose and lipid levels.

Conclusion: TLTG surgery is associated with superior clinical outcomes in the treatment of GC compared to LATG, particularly in reducing surgical trauma and accelerating postoperative recovery. Furthermore, TLTG facilitates the resolution of postoperative inflammatory responses and the amelioration of metabolic disorders. The findings from this investigation advocate for the broader adoption of TLTG in the surgical treatment of GC.

Objective: Colorectal carcinoma (CRC) is the third most common malignancy. In addition to comprehensive cancer treatments, such as surgery, chemotherapy, and radiotherapy, the adoptive immune cell therapy (ACT) has played an increasingly important role in recent years, and the adaptive transfusion of autologous NK cells and CIK cells is a brand-new approach to cellular therapy for solid tumors.

Case presentation: A 57-year-old man underwent a radical resection of microsatellite stable (MSS) rectal cancer with synchronous liver metastases. After surgery of the primary lesion surgery, he was treated with autologous CIK/NK cells combined with XELOX translational therapy. Each cycle can obtain over 10 × 10⁹ CIK cells or over 6 × 10⁹ NK cells combined chemotherapy of XELOX every 3 weeks. After 2 cycles of therapy, he achieved partial response (PR). He immediately underwent a hepatic metastasis resection. After surgery, the patient continued to receive autologous CIK/NK cells in combined with 4 cycles of XELOX. To date, he has achieved and maintained no evidence of disease (NED) for over 40 months.

Conclusion: This is a case of successful treatment of rectal cancer with liver metastasis using ACT in conjunction with first-line chemotherapy. The advantage of this treatment plan is that it has few side effects and achieves long-term control of tumor recurrence by improving the patient's immune function. However, its responsiveness and benefit rate still need further investigation.