Background: Bone metastasis frequently occurs in advanced breast cancer patients, and it is one of major causes of breast cancer associated mortality. The aim of the current study is to identify potential genes and related signaling pathways in the pathophysiology of breast cancer bone metastasis. Methods: Three mRNA expression datasets for breast cancer bone metastasis were obtained from Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were obtained. Functional analyses, protein-protein interaction (PPI) network, and transcription factors (TFs)-target genes network was constructed. Real-time PCR using clinical specimens was conducted to justify the results from integrated analysis. Results: A 749 DEGs were obtained. Osteoclast differentiation and rheumatoid arthritis were two significantly enriched signaling pathways for DEGs in the bone metastasis of breast cancer. SMAD7 (degree = 10), TGFBR2 (degree = 9), VIM (degree = 8), FOS (degree = 8), PDGFRB (degree = 7), COL5A1 (degree = 6), ARRB2 (degree = 6), and ITGAV (degree = 6) were high degree genes in the PPI network. ETS1 (degree = 12), SPI1 (degree = 12), FOS (degree = 10), FLI1 (degree = 5), KLF4 (degree = 4), JUNB (degree = 4), NR3C1 (degree = 4) were high degree genes in the TFs-target genes network. Validated by QRT-PCR, the expression levels of IBSP, MMP9, MMP13, TNFAIP6, CD200, DHRS3, ASS1, RIPK4, VIM, and PROM1 were roughly consistent with our integrated analysis. Except PROM1, the other genes had a diagnose value for breast cancer bone metastasis. Conclusions: The identified DEGs and signaling pathways may make contribution for understanding the pathological mechanism of bone metastasis from breast cancer.

Orbital rhabdomyosarcoma (RMS) is a relatively rare primary malignancy occurring in children. The objective of this study was to evaluate the cumulative incidence of cancer-specific death and competing risk of death among RMS patients after surgery and to build nomograms to predict overall survival (OS) and cancer-specific survival (CSS) based on a large population-based cohort. The records of 217 patients who were pathologically diagnosed with an orbital RMS between 1973 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively analyzed. The 10-, 20-, and 40-years OS rates and cancer-specific mortality were 82.5, 72.2, and 48.9%, respectively, and 14.8, 21.7, and 21.7%, respectively. The established nomograms were well-calibrated and validated, with a concordance index (C-index) of 0.901 and 0.944 for OS prediction, 0.923 and 0.904, for CSS prediction in the training and validation cohorts, respectively. The values of area under the receiver operating characteristic curve (AUC) for 10-, 20-, and 40-years OS and CSS prediction were 0.908, 0.826, and 0.847, and 0.924, 0.863, and 0.863, respectively. The established nomogram showed relatively good performances and could be convenient individualized predictive tools for prognostic prediction in RMS patients.

Recurrence and distant metastases were main reasons of unfavorable outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery. The aim of this study was to describe the patterns, timing, and predictors of recurrence or metastasis in PDAC patients after curative surgery. Patients with PDAC who underwent radical pancreatectomy were included. Associations between clinicopathological and radiological characteristics and specific pattern of progression were investigated. Least absolute shrinkage and selection operator (LASSO) and Cox regression were applied to assess the prognostic factors for overall survival (OS) and progression-free survival (PFS). A total of 302 patients were included into present study, and 173 patients were documented as recurrence after a median survival of 24.7 months. More than half of patients recurred after 12 months after surgery, and the liver was the most common metastatic site. Decreased time interval to progression, elevated carbohydrate antigen 19-9 (CA19-9) level, and lymph node (LN)16 metastasis were independent predictors for reduced OS. Independent prognostic factors for PFS included elevated carcinoembryonic antigen (CEA) level, local progression, liver or lung-only metastasis, local + distant progression, multiple metastases, LN16 metastasis, imaging tumor size, chemotherapy, and tumor-node-metastasis (TNM) stage. The predictive system showed valuable prediction performance with values of concordance indexes (C-indexes) and the area under the receiver operating characteristic curve (AUC) over 0.80. Different survival curves and predictive factors for specific patterns of disease progression suggested the biological heterogeneity, providing new versions into personal management of recurrence in PDAC patients after surgery.

We aimed to develop a copper-related gene (CRG) signature that can be used to evaluate prognosis and guide therapeutic management in bladder cancer patients.

Locally advanced pancreatic cancer (LAPC) has a dismal prognosis even after standard chemotherapy, and local progression contributes to nearly one-third of the deaths of these patients. As a local destructive method, irreversible electroporation (IRE) can feasibly treat LAPC. The aim of this study was to evaluate IRE combined with chemotherapy as a new treatment and compare its efficacy with that of chemotherapy alone in patients with LAPC. The data of LAPC patients who received chemotherapy with or without IRE were extracted from Surveillance, Epidemiology, and End Results (SEER) database and medical records of Sun Yat-sen University Cancer Center (SYSUCC). The efficacy of these two treatments was compared using propensity score matching (PSM) analysis. LAPC patients treated with the combination therapy had better overall survival (OS). Significantly higher cancer-specific survival (CSS) and progression-free survival (PFS) rates were also observed in patients after IRE combined with chemotherapy, compared with chemotherapy alone. IRE combined with chemotherapy was established as a favorable factor for OS, CSS, and PFS in LAPC patients. This combination method may be a more suitable treatment for patients with LAPC.

Locally advanced pancreatic cancer (LAPC) is a lethal disease and neoadjuvant chemotherapy and conversional resection is shown to provide the best survival for LAPC patients. Irreversible electroporation (IRE) is a new and effective method for the treatment of LAPC. This study aimed to compare the long-term survival of LAPC patients after neoadjuvant chemotherapy followed by conversional resection and IRE. A total of 140 LAPC patients were included from August 2015 to March 2020. The survival outcomes of patients after treatment with chemotherapy, chemotherapy combined with conversional resection or IRE were analyzed and compared. Patients in these three groups had similar clinical and pathological characteristics. Patients in the resection and IRE groups had similar median OS time (resection group vs. IRE group: 25.3 months vs. 26.0 months, P>0.050), which was significantly longer than that of the chemotherapy group (8.7 months, P<0.001). Additionally, patients in the resection and IRE groups had a median PFS of 10.6 and 12.0 months, respectively. Also, they were significantly higher than that of patients in the chemotherapy group. Chemotherapy combined with conversional resection and IRE was identified as significant prognostic factors for OS and PFS in LAPC patients. It was shown that compared with neoadjuvant chemotherapy followed by surgical resection, chemotherapy and IRE provided similar OS and PFS for LAPC patients with minimal invasion. This combination therapy may be a suitable treatment for LAPC patients.

This study assessed the predictive value of preoperative computed tomography (CT) scans and clinical factors for optimal debulking surgery (ODS) in patients with advanced ovarian cancer (AOC).

Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors with an insidious onset, difficult early diagnosis, and limited therapy options, resulting in a poor prognosis. Cell division cycle associated 2 (CDCA2), also known as Repo-Man, plays an important role in regulating mitosis and DNA repair, but the involvement of CDCA2 in HCC remains unclear.

To explore the MRI-based differential diagnosis of deep learning with data enhancement for cerebral glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and tumefactive demyelinating lesion (TDL).

Gastric cancer has one of the highest mortality rate in the world, but the treatment is still limited. Building on previous studies, mechanistic studies on propranolol in gastric cancer mice models and gastric cancer patients were performed. Propranolol inhibited the in vitro proliferation of gastric cancer cells in a time- and concentration-dependent manner. Consistent findings were observed in MFC tumors engrafted 615 mice, which were treated with propranolol at 10 mg/kg daily for 14 days. Propranolol inhibited the phosphorylation of AKT, MEK, and ERK proteins than control in mice tumor tissues respectively (p-AKT 26.16 vs. 56.82, P = 0.0196, p-MEK 28.27 vs. 59.28, P = 0.1102, p-ERK 48.2 vs. 107.4, P = 0.0062). Propranolol had antiproliferative activity in gastric cancer patients receiving 60 mg daily for 7 days prior to surgery(ki67 44.8 vs 125.3 for placebo; P = 0.02). Phosphorylated AKT, MEK, and ERK did not differ between propranolol and placebo treatment in gastric cancer patients. The expression of molecules on CD8+ T cells was not changed both in mice model and patients nor was there a statistically significant difference in CD8+ T cell subsets in patients, although suggestion of an effect was evident. These results prove that propranolol may inhibit the growth of gastric cancer in mice model and patients and the possible mechanism was via inhibiting the AKT and MAPK pathways, but the frequency of tumor infiltration CD8+ T cells did not increase significantly.

Urinary tumors primarily consist of kidney, urothelial, and prostate malignancies, which pose significant treatment challenges, particularly in advanced stages. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach, combining monoclonal antibody specificity with cytotoxic chemotherapeutic payloads. This review highlights recent advancements, opportunities, and challenges in ADC application for urinary tumors. We discuss the FDA-approved ADCs and other novel ADCs under investigation, emphasizing their potential to improve patient outcomes. Furthermore, we explore strategies to address challenges, such as toxicity management, predictive biomarker identification, and resistance mechanisms. Additionally, we examine the integration of ADCs with other treatment modalities, including immune checkpoint inhibitors, targeted therapies, and radiation therapy. By addressing these challenges and exploring innovative approaches, the development of ADCs may significantly enhance therapeutic options and outcomes for patients with advanced urinary tumor.

Long noncoding RNAs (lncRNAs) play a significant role in cancer biology. This study aimed to determine the roles of lncRNAs in establishing the differences in clinical features between patients with papillary thyroid carcinoma (PTC) without Hashimoto's thyroiditis (HT) and patients with PTC and HT. In the present study, we detected the differentially expressed lncRNAs between tumor tissues of patients with PTC with or without HT through lncRNA microarrays. The data were verified and analyzed through qRT-PCR, cell viability, cell cycle and bioinformatics analyses. We found that 1031 lncRNAs and 1338 mRNAs were abnormally expressed in 5 tissue samples of PTC complicated with HT [PTC/HT (+)] compared with 5 samples of PTC without HT [PTC/HT (-)]. Gene Ontology and pathway analyses of the mRNAs suggested that several biological processes and pathways, particularly immune system processes, were induced in the PTC/HT (+) tissues. Twenty lncRNAs were verified in 31 PTC/HT (+) and 64 PTC/HT (-) specimens by qRT-PCR, and the results were consistent with the microarray data. Specifically, ENST00000452578, a downregulated lncRNA in PTC/HT(+), was negatively correlated with the tumor size. Cell viability assays revealed that ENST00000452578 could inhibit cell proliferation. Our results indicate that lncRNAs and mRNAs play an important role in establishing the different clinical characteristics between patients with PTC/HT(+) and patients with PTC/HT(-), and might provide new insights from the perspective of RNA for obtaining a further understanding of the clinical features related to PTC with HT.

The radiotherapy outcomes of patients with advanced esophageal squamous cell carcinoma (ESCC) remain poor due to hypoxia. Carbonic anhydrase IX (CAIX) is a membrane-associated enzyme that induces hypoxia, extracellular acidity, and upregulation of hypoxia-related factors in tumor microenvironment, thereby promoting tumor metastasis. CAIX is upregulated in ESCC tissues compared to normal surrounding tissues. In the current study, we aimed to investigate the effect of CAIX inhibition on the modulation of tumor microenvironment and radiotherapy efficacy in ESCC. Higher CAIX expression was correlated with poorer progression-free survival in ESCC patients. Then, the ethyl N-(4-methylphenyl) sulfonylcarbamate (S4) was used to inhibit CAIX expression in ESCC cells and mice xenografts. The pretreatment of ESCC cells with S4 significantly downregulated CAIX expression, decreased intracellular pH, reduced cell viability, resulting in decreased oxygen consumption and more sensitive response to X-ray irradiation. In mice inoculated with ESCC cells, the combination of X-ray irradiation with S4 further improved survival, delayed tumor growth, decreased hypoxia level, exaggerated DNA damage, and increased apoptosis compared with the groups treated solely with S4 or radiotherapy. In conclusion, our study showed that the inhibition of CAIX by S4 treatment altered hypoxic tumor micro-environment, exaggerated DNA damage, increased apoptosis, and thus enhanced radiotherapy efficacy in ESCC. These findings provided a potential therapeutic strategy for patients with resistant ESCC.

Gliomas are the most common tumors of the central nervous system and are classified into grades I-IV based on their histological characteristics. Lower-grade gliomas (LGG) can be divided into grade II diffuse low-grade gliomas and grade III moderate gliomas and have a relatively good prognosis. However, LGG often develops into high-grade glioma within a few years. This study aimed to construct and identify the prognostic value of an inflammatory signature and discover potential drug targets for primary LGG. We first screened differentially expressed genes in primary LGG (TCGA) compared with normal brain tissue (GTEx) that overlapped with inflammation-related genes from MSigDB. After survival analysis, nine genes were selected to construct an inflammatory signature. LGG patients with a high inflammatory signature score had a poor prognosis, and the inflammatory signature was a strong independent prognostic factor in both the training cohort (TCGA) and validation cohort (CGGA). Compared with the low-inflammatory signature group, differentially expressed genes in the high-inflammatory signature group were mainly enriched in immune-related signaling pathways, which is consistent with the distribution of immune cells in the high- and low-inflammatory signature groups. Integrating driver genes, upregulated genes and drug targets data, bromodomain and PHD finger-containing protein 1 (BRPF1) was selected as a potential drug target. Inhibition of BRPF1 function or knockdown of BRPF1 expression attenuated glioma cell proliferation and colony formation.

Hypomethylating agents, decitabine (DAC) and azacitidine, can act as prophylactic and pre-emptive approaches after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a non-intensive bridging approach before allo-HSCT. However, they are rarely used as a part of conditioning regimens in patients with relapsed or refractory acute myeloid leukemia (AML). This retrospectively study included a total of 65 patients (median, 37; range, 13-63) with relapsed or refractory AML who were treated by allo-HSCT after myeloablative conditioning regimens without or with DAC (high-dose DAC schedule, 75 mg/m2 on day -9 and 50 mg/m2 on day -8; low-dose DAC schedule, 25 mg/m2/day on day -10 to -8). DAC exerted no impact on hematopoietic reconstitution. However, patients who were treated with the high-dose DAC schedule had significantly higher incidence of overall survival (OS, 50.0%) and leukemia-free survival (LFS, 35.0%), and lower incidence of relapse (41.1%) and grade II-IV acute graft versus host disease (aGVHD, 10.0%) at 3 years, when compared with those treated with standard conditioning regimens or with the low-dose DAC schedule. In conclusion, high-dose DAC combined with standard conditioning regimens before allo-HSCT is feasible and efficient and might improve outcomes of patients with relapsed or refractory AML, which provides a potential approach to treat these patients.

Both omacetaxine (HHT) and curcumin were shown to exhibit anti-proliferative effect on lymphoma cells. However, the role of combination of HHT with curcumin (HHT/curcumin combination) on lymphoma cells remains unclear. Thus, this study aimed to investigate the effect of HHT/curcumin combination on the proliferation, migration, and angiogenesis of lymphoma cells.

The hypoxic tumor microenvironment was reported to be involved in different tumorigenesis mechanisms of triple-negative breast cancer (TNBC), such as invasion, immune evasion, chemoresistance, and metastasis. However, a systematic analysis of the prognostic prediction models based on multiple hypoxia-related genes (HRGs) has not been established in TNBC before in the literature. We aimed to develop and verify a hypoxia gene signature for prognostic prediction in TNBC patients.

To develop a machine learning (ML)-based classifier for discriminating between low-grade (ISUP I-II) and high-grade (ISUP III-IV) clear cell renal cell carcinomas (ccRCCs) using MRI textures.

Irreversible electroporation (IRE) is a novel method which was especially suitable for the treatment of locally advanced pancreatic cancer (LAPC). The purpose of this study was to evaluate probabilities of overall survival (OS) and cancer-specific survival (CSS) in patients with LAPC after IRE treatment and to construct nomograms to predict survival for these patients. Data of patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database and medical records of Sun Yat-sen University Cancer Center (SYSUCC). A total of 312 LAPC patients after IRE treatment were included into this study. The 3-year cumulative incidence of cancer-specific mortality for patients with LAPC after IRE treatment was 74.3%. Nomograms for predicting probabilities of OS, CSS, and non-cancer-specific survival (NCSS) were built and calibrated with the concordance index (C-index) and the area under receiver operating characteristic (ROC) curve (AUC). The established nomograms were well-calibrated, with C-indexes of 0.782 for OS prediction, 0.729 for CSS prediction, and 0.730 for NCSS prediction. Compared with the TNM stage system, the established nomograms displayed higher values of AUC and showed better discriminatory power for predicting OS, CSS, and NCSS. These nomograms were well-calibrated and could serve to guide management of LAPC patients after IRE treatment.

Pancreatic adenocarcinoma of the body and tail often has a dismal prognosis and lacks a specific prognostic stage. The aim of this study was to construct a nomogram for predicting survival of patients with pancreatic adenocarcinoma of the body and tail after surgery. Data of patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database and from medical records of Sun Yat-sen University Cancer Center (SYSUCC). In a multivariate analysis for overall survival (OS), the following six variables were identified as independent predictors and incorporated into the nomogram: age, tumor differentiation, tumor size, lymph node ratio (LNR), and chemotherapy. A nomogram was built based on independent risk predictors. The concordance index (C-index) for nomogram, Tumor-Node-Metastasis (TNM) 7th and 8th stage system were 0.775 [95% confidence interval (CI), 0.731-0.819], 0.617 (95%CI, 0.575-0.659), and 0.632 (95%CI, 0.588-0.676), respectively. The calibrated nomogram predicted survival rates which closely corresponded to the actual survival rates. Furthermore, the values of the area under receiver operating characteristic (ROC) curves (AUC) of the nomograms were higher than those of the TNM 7th or 8th stage system in predicting 1-, 2-, and 3-year survival of patients in training and external validation cohorts. The well-calibrated nomogram could be used to predict prognosis for patients with pancreatic adenocarcinoma of the body and tail after surgery.