Journal of Cancer Research and Clinical Oncology最新文献

Purpose

This study aims to utilize bioinformatics methods to systematically screen and identify susceptibility genes for cervical cancer, as well as to construct and validate an mitophagy-related genes (MRGs) diagnostic model. The objective is to increase the understanding of the disease’s pathogenesis and improve early diagnosis and treatment.

Method

We initially collected a large amount of genomic data, including gene expression profile and single nucleotide polymorphism (SNP) data, from the control group and Cervical cancer (CC) patients. Through bioinformatics analysis, which employs methods such as differential gene expression analysis and pathway enrichment analysis, we identified a set of candidate susceptibility genes associated with cervical cancer.

Results

MRGs were extracted from single-cell RNA sequencing data, and a network graph was constructed on the basis of intercellular interaction data. Furthermore, using machine learning algorithms, we constructed a clinical prognostic model and validated and optimized it via extensive clinical data. Through bioinformatics analysis, we successfully identified a group of genes whose expression significantly differed during the development of CC and revealed the biological pathways in which these genes are involved. Moreover, our constructed clinical prognostic model demonstrated excellent performance in the validation phase, accurately predicting the clinical prognosis of patients.

Conclusion

This study delves into the susceptibility genes of cervical cancer through bioinformatics approaches and successfully builds a reliable clinical prognostic model. This study not only helps uncover potential pathogenic mechanisms of cervical cancer but also provides new directions for early diagnosis and treatment of the disease.

Purpose: The retrospective study was to explore the effectiveness and safety of GemOx (gemcitabine, oxaliplatin) plus sintilimab (belongs to the class of drugs known as immune checkpoint inhibitors, particularly targeting the PD-1 receptor) in relapse or refractory nodal PTCLs.

Methods: Patients with nodal PTCL who initiated salvage therapy with sintilimab and GemOx between January 2020 to September 2021 were identified from the database of the hematology department of the Second Affiliated Hospital of Zhejiang University School of Medicine. All patients received 2-4 cycles (3 weeks/cycle) of treatment of sintilimab (200 mg, I.V, D1) in combination with GemOx. Treatment response was assessed every six weeks during the salvage treatment phase. Eligible patients received maintenance therapy according to the investigator's decision. Follow-ups were routinely conducted every three months.

Results: 31 patients with r/r nodal PTCLs were enrolled, including 23 PTCL-NOS, 4 AITL, and 4 ALCL. 21 (67.7%) patients received at least two lines of therapy. 71.0% (95% CI, 53.4%-83.9%) of patients documented objective response of 2-4 cycles of sintilimab plus GemOx therapy, including 9 complete response and 13 partial response. 21 (67.7%) patients received consolidation therapy, including 5 autologous stem-cell transplantation and 12 histone deacetylase inhibitors. After a median 25.6 months follow-up, the median PFS was 22.0 (95% CI,11.8-24.7) months, and the median OS was 26.2 (95% CI, 24.4 -NA) months. 29 (93.5%) patients experienced at least one adverse event, and 26 (83.9% patients only had mild (grade 1-2) AEs.Univariable Cox regression showed the progression risk of AITL is 22.7 (3.9- 131.0, p < 0.01) times of PTCL-NOS, while the HR of ALCL was 1.14 (0.33-3.96,p = 0.833).

Conclusion: Sintilimab plus GemOx showed encouraging activity and manageable toxicity for patients with r/r PTCL.

Purpose

This research aimed to evaluate the expression level of Homeobox A9 (HOXA9) and its role in tumorigenesis of hepatocellular carcinoma (HCC).

Methods

Bioinformatic analysis, qPCR and Western blot analysis of clinical samples were employed to evaluate mRNA and protein levels of HOXA9 in HCC patients and cell lines. In vitro cell proliferation, migration and invasion, cloning formation, xenograft tumor model, wound healing and apoptosis assays, RNA sequencing analysis of RPL38-silenced HCC-LM3 cells and qPCR, Western blot analysis were performed for validation. Analysis of HOXA9-related genes were conducted to identify their relationships between HOXA9.

Results

HOXA9 is dramatically upregulated in HCC. Upregulation of HOXA9 in HCC predicts poor survival of patients. Besides, HOXA9 promotes proliferation, metastasis and prevents apoptosis in HCC in vitro. In addition, HOXA9 controlled by Ribosomal protein RPL38 is upregulated in HCC. Bioinformatic analysis also indicated that HOXA9 is involved in the regulation of DNA methylation and immune infiltration in HCC.

Conclusion

HOXA9 is dramatically upregulated in hepatocellular carcinoma and predicts poor prognosis. Besides, HOXA9 promoted proliferation and metastasis and prevented apoptosis in vitro, which is regulated by Ribosomal protein RPL38 in HCC.

Background

This study aims to establish a predictive model for assessing the risk of esophageal cancer lung metastasis using machine learning techniques.

Methods

Data on esophageal cancer patients from 2010 to 2020 were extracted from the surveillance, epidemiology, and end results (SEER) database. Through univariate and multivariate logistic regression analyses, eight indicators related to the risk of lung metastasis were selected. These indicators were incorporated into six machine learning classifiers to develop corresponding predictive models. The performance of these models was evaluated and compared using metrics such as The area under curve (AUC), accuracy, sensitivity, specificity, and F1 score.

Results

A total of 20,249 confirmed cases of esophageal cancer were included in this study. Among them, 14,174 cases (70%) were assigned to the training set while 6075 cases (30%) constituted the internal test set. Primary site location, tumor histology, tumor grade classification system T staging criteria N staging criteria brain metastasis bone metastasis liver metastasis emerged as independent risk factors for esophageal cancer with lung metastasis. Amongst the six constructed models, the GBM algorithm-based machine learning model demonstrated superior performance during internal dataset validation. AUC, accuracy, sensitivity, and specificity values achieved by this model stood at respectively at 0.803, 0.849, 0.604, and 0.867.

Conclusion

We have developed an online calculator based on the GBM model (https://lvgrkyxcgdvo7ugoyxyywe.streamlit.app/)to aid clinical decision-making and treatment planning.

Background

Hepatocellular carcinoma (LIHC) has severe consequences due to late diagnosis and the lack of effective therapies. Currently, potential biomarkers for the diagnosis and prognosis of LIHC have not been systematically evaluated. Previous studies have reported that RAC1 is associated with the B cell receptor signaling pathway in various tumor microenvironments, but its relationship with LIHC remains unclear. We investigated the relationship between RAC1 and the prognosis and immune infiltration microenvironment of LIHC, exploring its potential as a prognostic biomarker for this type of cancer.

Methods

In this study, we analyzed data from The Cancer Genome Atlas (TCGA) using the Wilcoxon signed-rank test and logistic regression to assess the association between RAC1 expression and clinical characteristics in LIHC patients. Additionally, Kaplan-Meier and Cox regression methods were employed to confirm the impact of RAC1 expression levels on overall survival. Immunohistochemistry was used to validate RAC1 protein expression in LIHC. We constructed RAC1 knockdown LIHC cells and studied the effects of RAC1 protein on cell proliferation and migration at both cellular and animal levels.

Results

RAC1 expression levels were significantly elevated in LIHC tissues compared to normal tissues. High RAC1 expression was strongly associated with advanced pathological stages and was identified as an independent factor negatively affecting overall survival. At both cellular and animal levels, RAC1 knockdown significantly inhibited the proliferation and migration of LIHC cells. Furthermore, RAC1 expression was positively correlated with the infiltration of Th2 cells and macrophages in the tumor microenvironment, suggesting that RAC1 may contribute to the deterioration of the tumor immunosuppressive microenvironment and potentially lead to reduced patient survival.

Conclusion

These findings indicate that RAC1 expression promotes LIHC proliferation and migration and influences the landscape of immune cell infiltration in the tumor microenvironment. Based on these results, RAC1 is proposed as a potential prognostic biomarker for LIHC, associated with both cancer progression and tumor immune cell infiltration.

Background and Objectives

Circadian rhythms, the endogenous biological clocks that govern physiological processes, have emerged as pivotal regulators in the development and progression of breast cancer. This comprehensive review delves into the intricate interplay between circadian disruption and breast tumorigenesis from multifaceted perspectives, encompassing biological rhythms, circadian gene regulation, tumor microenvironment dynamics, and genetic polymorphisms.

Methods and Results

Epidemiological evidence underscores the profound impact of external factors, such as night shift work, jet lag, dietary patterns, and exercise routines, on breast cancer risk and progression through the perturbation of circadian homeostasis. The review elucidates the distinct roles of key circadian genes, including CLOCK, BMAL1, PER, and CRY, in breast cancer biology, highlighting their therapeutic potential as molecular targets. Additionally, it investigates how circadian rhythm dysregulation shapes the tumor microenvironment, fostering epithelial-mesenchymal transition, chronic inflammation, and immunosuppression, thereby promoting tumor progression and metastasis. Furthermore, the review sheds light on the association between circadian gene polymorphisms and breast cancer susceptibility, paving the way for personalized risk assessment and tailored treatment strategies.

Conclusions

Importantly, it explores innovative therapeutic modalities that harness circadian rhythms, including chronotherapy, melatonin administration, and traditional Chinese medicine interventions. Overall, this comprehensive review emphasizes the critical role of circadian rhythms in the pathogenesis of breast cancer and highlights the promising prospects for the development of circadian rhythm-based interventions to enhance treatment efficacy and improve patient outcomes.

Purpose

To support doctors in counselling women with genetic predisposition for breast or gynecologic cancers on endocrine interventions.

Methods

Evidence on the safety of endocrine interventions for fertility treatment, contraception, hormone replacement therapy after risk-reducing salpingo-oophorectomy (RRSO) or treatment of symptoms during peri- and postmenopause was analysed for carriers of probably pathogenic and pathogenic variants in BRCA1 or BRCA2 (BRCA1/2-pV), in other breast and ovarian cancer genes and the Lynch Syndrome. Cancer risks were compared with data on risks for the general population.

Results

Data on risk modulation of endocrine interventions in women with genetic predisposition is limited. Ovarian hyperstimulation for fertility treatment may be performed. Oral contraceptives should not be used to reduce ovarian cancer risk in BRCA1/2-pV carriers. Premenopausal BRCA1/2-pV carriers and carriers of pV in Lynch Syndrome genes should be offered hormone replacement therapy (HRT) after RRSO, to prevent diseases caused by estrogen deficiency.

Conclusion

Effect direction and strength of risk modulation by endocrine interventions is similar to the general population. Participation of individuals at risk in prospective registries is recommended.

Background: Gastric cancer (GC), a prevalent malignant tumor which is a leading cause of death from malignancy around the world. Peritoneal metastasis accounts for the major cause of mortality in patients with GC. Despite hyperthermia intraperitoneal chemotherapy (HIPEC) improves the therapeutic effect of GC, it's equivocal about the mechanism under HIPEC.

Methods: MiR-183-5p expression was sifted from miRNA chip and detected in both GC patients and cell lines by qRT-PCR. Gene interference and rescue experiments were performed to identified biological function in vitro and vivo. Next, we affirmed PPP2CA as targeted of miR-183-5p by dual luciferase reporter assay. Finally, the potential relationship between HIPEC and miR-183-5p was explored.

Results: MiR-183-5p is up-regulated in GC and associated with advanced stage and poor prognosis. MiR-183-5p accelerate GC migration in vitro which is influenced by miR-183-5p/PPP2CA/AKT/GSK3β/β-catenin Axis. HIPEC exerts migration inhibition via attenuating miR-183-5p expression.

Conclusion: MiR-183-5p can be used as a potential HIPEC biomarker in patients with CC.

Purpose: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Nevertheless real-world data are limited. The aim of this multicenter study was to generate real-world data from nmCRPC patients treated with ADT plus apalutamide.

Methods: In this observational cohort based investigator initiated trial data of nmCRPC patients receiving apalutamide plus ADT were collected focusing on patient demographic data, prostate-specific antigen (PSA) declines, safety profile including dose modification/discontinuation as well as subsequent therapy and metastasis-free survival (MFS).

Results: Data from a total of 31 nmCRPC patients were documented. Compared to the Phase III study Spartan real-world patients are older, showed a higher ECOG-PS and more aggressive tumors. In the cohort PSA decreased about 98.1%, 74% of patients showed a PSA decrease over 90% and 54.8% reached a PSA-level < 0.2ng/ml. Apalutamide was well tolerated in real world patients: adverse events occurred in 67.7% but were in the majority mild (≥ grade 3: 6.5%). Dose reduction was necessary in 38.7% and 32.2% discontinued apalutamide treatment. MFS was 43 months and majority of patients were subsequently treated with abiraterone.

Conclusion: In real world more comorbid nmCRPC patients with a higher ECOG-PS and more aggressive tumors are treated with apalutamide plus ADT. Nevertheless efficacy results as well as side effects are similar in real-world compared to Spartan trial showing also a rapid, durable and deep PSA response with a median MFS of 43 months.