Clinical and Experimental Medicine最新文献

Understanding the metastatic cascade is critical for the treatment and prevention of cancer-related death. Within a tumor, immune cells have the capacity to fuse with tumor cells to generate tumor-immune hybrid cells (THCs). THCs are hypothesized to be a subset of cancer cells with the capacity to enter circulation as circulating hybrid cells (CHC) and seed metastases. To understand the mechanism of THC metastasis, we investigated CHCs in peripheral blood from patients with stage IV colorectal cancer (CRC), as well as THCs in tissues of primary colorectal cancers and their liver metastasis sites using immunofluorescence, spatial proteomic, spatial transcriptomic, molecular classification, and molecular pathway analyses. Our findings indicated a high prevalence of CHCs and THCs in patients with stage IV CRC. THCs expressed CTLA4 in primary CRC lesions and correlated with upregulation of CD68, CD4, and HLA-DR in metastatic liver lesions, which is found in the consensus molecular subtype (CMS) 1 of primary CRC tissue. Pathway analysis of these genes suggested that THCs are associated with neutrophils due to upregulation of neutrophil extracellular trap signaling (NET) and neutrophil degranulation pathways. These data provide molecular pathways for the formation of THCs suggesting fusion with neutrophils, which may facilitate extravasation and metastatic seeding.

This study was to develop and validate a model for predicting who can benefit from multiple transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients.228 and 98 patients were included in the development and validation sets, respectively. The primary clinical endpoint was benefiting from consecutive multiple TACE treatments. Logistic regression analysis was used to screen the independent risk factors for the clinical endpoint. The independent risk factors were then used to construct the predictive model. The area under receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves were used to evaluate the predictive ability of the model.Multivariate Logistic regression analysis showed that complete envelope, hepatic lopes, tumor number, and alpha-fetoprotein (AFP) were independent risk factors for benefiting from multiple TACE in HCC patients. The area under the curve (AUC) of the model constructed by using independent risk factors in the development and validation sets was 0.843 (95% confidence interval [CI]: 0.784-0.902) and 0.828 (95%CI: 0.739-0.916), respectively. The calibration curves and clinical decision curves showed that the model had good predictive ability.The model established in this study has a good predictive effect on HCC patients who can benefit from multiple TACE.

Colorectal cancer is a leading cause of global mortality and presents a significant barrier to improving life expectancy. The primary objective of this study was to discern a unique differentially expressed gene (DEG) that exhibits a strong association with colorectal cancer. By achieving this goal, the research aims to contribute valuable insights to the field of translational medicine. We performed analysis of colorectal cancer microarray and the TCGA colon adenoma carcinoma (COAD) datasets to identify DEGs associated with COAD and common DEGs were selected. Furthermore, a pan-cancer analysis encompassing 33 different cancer types was performed to identify differential genes significantly expressed only in COAD. Then, comprehensively in-silico analysis including gene set enrichment analysis, constructing Protein-Protein interaction, co-expression, and competing endogenous RNA (ceRNA) networks, investigating the correlation between tumor-immune signatures in distinct tumor microenvironment and also the potential interactions between the identified gene and various drugs was executed. Further, the candidate gene was experimentally validated in tumoral colorectal tissues and colorectal adenomatous polyps by qRael-Time PCR. GUCA2A emerged as a significant DEG specific to colorectal cancer (|log2FC|> 1 and adjusted q-value < 0.05). Importantly, GUCA2A exhibited excellent diagnostic performance for COAD, with a 99.6% and 78% area under the curve (AUC) based on TCGA-COAD and colon cancer patients. In addition, GUCA2A expression in adenomatous polyps equal to or larger than 5 mm was significantly lower compared to smaller than 5 mm. Moreover, low expression of GUCA2A significantly impacted overall patient survival. Significant correlations were observed between tumor-immune signatures and GUCA2A expression. The ceRNA constructed included GUCA2A, 8 shared miRNAs, and 61 circRNAs. This study identifies GUCA2A as a promising prognostic and diagnostic biomarker for colorectal cancer. Further investigations are warranted to explore the potential of GUCA2A as a therapeutic biomarker.

Minimal residual disease (MRD) is of growing interest in light chain (AL) amyloidosis and is associated with higher rates of cardiac response. A new graded cardiac response criteria has been proposed for better assessment of cardiac improvement. We evaluated MRD status in 63 patients with cardiac AL amyloidosis using next generation flow cytometry (sensitivity ≥ 1*10^-5) within four cycles after treatment initiation and cardiac response kinetics. All patients were treated with first-line proteasome inhibitor (100%) and predominantly bortezomib (87.3%). The overall early MRD negative rates were 33.3%. Patients who achieved early MRD negativity were less likely to harbor t(11;14) (21.1% vs 57.5%, P = 0.009). The MRD negative rates amongst patients in hematologic complete response were 66.7% (14/21), and in very good partial response 29.2% (7/24). Early MRD negativity was associated with a higher likelihood of achieving ≥ cardiac partial response (≥ CarPR) (66.7% vs 38.1%, P = 0.032) and ≥ cardiac very good partial response (≥ CarVGPR) (38.1% vs 11.9%, P = 0.023) throughout first-line therapy. The cumulative incidence curve of achieving ≥ CarPR (P = 0.034) and ≥ CarVGPR (P = 0.026) showed significant difference between early MRD negative and positive group. After a median follow-up time of 27.2 months, the median progression free survival was longer in early MRD negative group (not reached vs 31.3 months, P = 0.033). Early MRD eradication in cardiac AL amyloidosis generated deeper and faster cardiac organ response.

Colorectal cancer (CRC) ranks among the most prevalent malignant tumors worldwide, with a multifactorial etiology encompassing genetic, environmental, and life-style factors, as well as the intestinal microbiota and its metabolome. These risk factors often work together in specific groups of patients, influencing how CRC develops and progresses. Importantly, alterations in the gut microbiota act as a critical nexus in this interplay, significantly affecting susceptibility to CRC. This review highlights recent insights into unmodifiable and modifiable risk factors for CRC and how they might interact with the gut microbiota and its metabolome. Understanding the mechanisms of these interactions will help us develop targeted, precision-medicine strategies that can adjust the composition of the gut microbiota to meet individual health needs, preventing or treating CRC more effectively.

We aimed to investigate the risk of bladder cancer (BCa) survivors developing or dying from 15 specific-subsequent primary cancers (SPCs). A total of 229,554 BCa survivors were identified from the Surveillance, Epidemiology, and End Results database. Incidence and mortality per 10,000 person-years, absolute excess risk (AER) per 10,000 person-years, standardized incidence ratios, and standardized mortality ratios were calculated. Among BCa survivors, 38,207 developed SPCs and 17,546 died of SPCs. The risk of developing and dying from SPCs was significantly high for 10 and 6 of the 12 common SPCs in men, respectively, while for 6 and 5 of the 14 common SPCs in women, respectively. The SPCs with high risk of development in men were colorectal, breast, liver, and pancreatic cancer, and the ones with high risk of death were liver and pancreatic cancer. Moreover, SPCs with a high risk of development or death among young BCa survivors include ureter, kidney and renal pelvis, and lung cancer. In addition, BCa survivors within 1 year of diagnosis have a significantly higher risk of development and death from ureter, kidney and renal pelvis, prostate, and cervix cancer, but a lower risk of prostate cancer than the general population after 5 years of diagnosis. Lung cancer had a significantly high risk of development but a low risk of death. Among BCa survivors, the risk of developing or dying from few SPCs is significantly high. These findings may provide an important basis for clinical follow-up of BCa survivors.

Hepatocellular carcinoma (HCC) recurrence appears commonly after liver transplantation (LT), and it severely affected the long-term survival of patients. Previous studies have proved that Rap1A is involved in hepatocarcinogenesis and metastasis, and demonstrated the significant association between KRAS rs712 polymorphism and HCC. However, the relationship between KRAS rs712 polymorphism and HCC recurrence after LT remained unclear. A total of 93 HCC patients who underwent LT from March 2008 to Dec 2015 was analyzed. The genotypes of both donors and recipients had been confirmed as KRAS rs712. The independent risk factors that associated with HCC recurrence were investigated with univariate and multivariate logistic regression analysis. The recurrence-free (RFS) and overall survival (OS) were calculated with Cox regression analysis. The KRAS rs712 genotype frequencies were determined using the Χ² test and the minor allele frequencies (MAFs) of KRAS rs712 genotypes were calculated by Hardy-Weinberg equilibrium. We found that the recipient KRAS rs712 polymorphism was significantly associated with HCC recurrence after LT. Moreover, the Milan criteria, microvascular invasion and recipient KRAS rs712 genotype were proved to be independent risk factors for HCC recurrence after LT. Patients with donor TG/TT genotypes had a significantly higher RFS and OS than TT genotype. The TNM stage, microvascular invasion, Milan criteria, treatment and recipient KRAS rs712 genotype were independent factors for the RFS of LT patients. Recipient KRAS rs712 polymorphism is associated with HCC recurrence after liver transplantation and plays as a promising bio-predictor of overall survival rate of HCC risks after hepatic transplantation.

The most common type of non-small cell lung cancer is lung adenocarcinoma (LUAD), which is characterized by high morbidity and poor survival. Up-regulation of SASS6 expression can lead to the progression of various malignant tumors. However, there are no relevant studies on the role of SASS6 in LUAD. SASS6 was highly expressed in most tumors, reflecting a good diagnostic value, and its overexpression in LUAD indicated discouraging overall prognosis. Functional enrichment analysis suggested that SASS6 was associated with cell cycle in LUAD. In addition, patients with high SASS6 expression had worse immune infiltration, but higher TMB and immune checkpoint, and higher sensitivity to multiple targeted drugs such as osimertinib. Cell experiments confirmed that knockdown of SASS6 could inhibit the viability of tumor cells.SASS6 has important value in the diagnosis of cancer. In particular, SASS6 is a crucial factor in the progression of LUAD, and has important clinical value, especially in the diagnosis, prognosis and treatment.