Journal of Cancer Research and Clinical Oncology最新文献

Purpose: The rarity of breast mucinous carcinoma (BMC) makes it challenging to study the prognosis of this disease across diverse racial populations. This study aimed to leverage epidemiological data on immigrant populations to elucidate the prognostic differences in BMC patients from various racial/ethnic backgrounds. The goal was to help formulate more personalized clinical practice guidelines for the management of this rare malignancy.

Methods: The study included 208 BMC patients from China and 10,322 BMC patients from the SEER database. Clinicopathological data, treatment information, and survival outcomes were compared across different racial/ethnic groups using statistical analyses.

Results: Asian American BMC patients were younger at diagnosis and had more favorable tumor grade and stage compared to other racial groups. After adjusting for clinicopathological factors and treatments, Asian American BMC patients exhibited significantly better overall survival (OS) than black (HR = 1.53, 95% CI: 1.05-2.22, P = 0.027) and white patients (HR = 1.41, 95% CI: 1.03-1.94, P < 0.001). Specifically, non-Chinese American patients had a worse OS compared to Chinese patients (adjusted HR = 2.59, 95% CI: 1.15-5.83, P = 0.022). Chemotherapy significantly improved OS only in black BMC patients (adjusted HR = 0.52, 95% CI: 0.27-0.98, p = 0.045), but not in other racial/ethnic groups.

Conclusion: Race is an independent prognostic factor for BMC. Compared with Chinese patients, black and white American patients have a worse prognosis in terms of OS. Treatment guidelines for BMC patients should be formulated with considerations of race factors. For patients with BMC originating from China, a more conservative treatment approach may be warranted.

Purpose: The objective of the current research was to assess the clinicopathological characteristics and long-term prognosis of triple-negative breast cancer (TNBC) patients with human epidermal growth factor receptor 2 (HER2)-low status following breast surgery.

Methods: A total of 202 TNBC patients treated at Qingdao Central Hospital from January 2010 to December 2019 were included, comprising 71 HER2-low and 131 HER2-zero patients. Propensity score matching (PSM) was applied to minimize differences between the cohorts.

Results: HER2-low TNBC patients had lower histological grade, lower Ki-67 expression levels, and a higher prevalence of hypertension compared to HER2-zero TNBC patients. Before and after PSM, the HER2-low group consistently exhibited a lower recurrence rate and longer RFS compared to HER2-zero TNBC patients. HER2-low status was validated as an independent low-risk factor for RFS both pre-PSM (HR 0.354, 95% CI 0.178-0.706, p = 0.003) and post-PSM (HR 0.405, 95% CI 0.185-0.886, p = 0.024). No statistically significant differences in mortality rate and OS were observed, both before and after PSM.

Conclusions: HER2-low and HER2-zero TNBC patients show significant clinicopathological differences. Compared to HER2-zero, HER2-low status is linked to better long-term prognosis and serves as an independent low-risk factor for RFS in TNBC patients.

Purpose: This study aims to investigate the biological roles and molecular mechanisms of Cathepsin G (CTSG) in the progression of non-small cell lung cancer (NSCLC).

Methods: Western blotting and immunohistochemistry analyses of clinical samples were performed to determine the expression levels of CTSG in patients with NSCLC. Bioinformatic analysis of clinical datasets was conducted to evaluate the correlation between CTSG and lymph node metastasis, tumor stage, and immune cell infiltration. Gain-of-function assays and tumor implantation experiments were employed to determine the effects of CTSG on malignant behaviors of NSCLC cells. Transcriptome sequencing and subsequent bioinformatic analysis were performed to explore the signaling pathways regulated by CTSG. Western blotting and qPCR were utilized to assess the influence of CTSG on the MAPK and EMT signaling pathways.

Results: CTSG is expressed at low levels and serves as a prognostic marker in NSCLC. The downregulation of CTSG expression was associated with lymph node metastasis, tumor stage, and immune cell infiltration. CTSG inhibits NSCLC cell proliferation, migration, and invasion as well as tumor growth in nude mice. There exists a significant correlation between CTSG expression and endoplasmic reticulum function, cell cycling, and the IL-17 signaling pathway. CTSG suppresses the MAPK and EMT signaling pathways in NSCLC cells. Moreover, DNA methylation and histone deacetylation have been identified as crucial mechanisms contributing to the decreased expression of CTSG.

Conclusion: CTSG inhibits NSCLC development by suppressing the MAPK signaling pathway and is also associated with tumor immunity.

Purpose: Adolescent and young adult cancer survivors (AYA-CS) face a long working life after treatment, yet factors related to a successful return to work remain largely unexplored. We therefore aimed to investigate the use of occupational adjustments and their impact on work ability upon return to work.

Methods: As part of the AYA-LE study, we surveyed AYA-CS (aged 18-39 at diagnosis) who returned to work and assessed work ability (Work Ability Index) as well as use and benefit of occupational adjustments. We analyzed predictors of use and benefit of occupational adjustments on average 4 years post-diagnosis using multivariate linear and logistic regression.

Results: Out of 438 AYA-CS, 389 (88.8%) returned to work after cancer diagnosis and were included in analyses. Mean work ability was M = 36.2 (SD = 6.9), 11.4% reported poor, 34.7% moderate, 41.4% good and 12.5% excellent work ability. Following treatment, 82.3% used occupational adjustments, most frequently: flexible working hours, gradual reintegration and reduced working hours. The probability of a reduction in working hours was found to be higher among older AYA-CS (≥ 30), female gender and with a fatigue index ≥ 11 (R2 = 0.073). A fatigue index < 11, elevated levels of pain and the presence of metastases/recurrence were associated with a lower benefit of reduced working hours (R2 = 0.183). Younger age (< 30) and stem cell transplant were associated with a lower benefit of support from colleagues (R2 = 0.077).

Conclusion: Our results highlight the need for targeted occupational counselling throughout the treatment and even beyond the return-to-work process, considering individual and social factors.

Objective: To investigate the mechanism by which heterogeneity in breast cancer developed and acted in single-cell transcriptomes.

Methods: The composition of breast cancer based on the single-cell transcriptomes of 54,055 high-quality cells from clinical specimens of 4 malignant and 4 non-malignant patients were investigated.

Results: We identified six common expression programs and six subtype-specific expression programs form malignant epithelial cells. The expression program of malignant epithelial cells exhibited activated EMT (Epithelial Mesenchymal Transition) in TME, which might indicate EMT intervention have a general therapeutic effect on various subtypes. Gene set enrichment analysis (GSEA) based on the top 50 highly NMF (non-negative matrix factorization) score genes in each program depicted the distinct function of each program in breast cancer progression. Moreover, we revealed the profound cellular heterogeneity of myeloid cell lineages in breast cancer. In macrophages, two mainly tumor associated macrophages (TAMs), TAM1 and TAM2, were also detected and the highly variable genes in TAM2 were strongly enriched in IFN-α and IFN-γ. The changes of lipid metabolism pathways in macrophages are closely related to the microenvironment of breast cancer.

Conclusion: We constructed a comprehensive single-cell transcriptome atlas of 54,055 cells from 4 malignant and 4 nonmalignant patients, providing insights into the mechanisms underlying breast cancer progression and the development of potential therapeutic strategies in breast cancer.

Purpose: This study aimed to investigate that AKT1-Mediated NOTCH1 phosphorylation promotes gastric cancer (GC) progression via targeted regulation of IRS-1 transcription.

Methods: The study utilized databases such as PhosphositePlus, TRANSFAC, CHEA, GPS 5.0, and TCGA, along with experimental techniques including Western Blot, co-IP, in vitro kinase assay, construction of lentiviral overexpression and silencing vectors, immunoprecipitation, modified proteomics, immunofluorescence, ChIP-PCR, EdU assay, Transwell assay, and scratch assay to investigate the effects of AKT1-induced Notch1 phosphorylation on cell proliferation, invasion and migration in vitro, as well as growth and epithelial-mesenchymal transition (EMT) in vivo.

Results: AKT1 was found to induce phosphorylation of Notch1 at the S2183 site in GC, subsequently altering the subcellular localization of Notch1-IC and promoting its nuclear translocation. The transcription factor RBPJ that binds to Notch1 transcriptionally regulated IRS-1, CDH5, TNL1, ASCL2, and LRP6. Experimental validation revealed that Notch1-IC can regulate the expression of IRS-1. Overexpression of Notch1-IC was shown to promote the proliferation, invasion, and metastasis of GC cells, while knockdown of IRS-1 partially inhibited the aforementioned effects induced by Notch1-IC overexpression. Further experiments in vitro and vivo confirmed that AKT1-induced Notch1 phosphorylation can regulate the expression of IRS-1 and promote the malignant behavior of GC, including proliferation, invasion, metastasis, and EMT, with knockdown of IRS-1 partially reversing these effects.

Conclusion: AKT1 induces the Notch1 phosphorylation and promotes the activation and nuclear translocation of Notch1-IC by targeting the regulation of IRS-1, thereby advancing the progression of GC.

Background: FOXF2 was reported to involve in a variety of biological behaviors that include the development of the central nervous system, tissue homeostasis, epithelia-mesenchymal interactions, regulation of embryonic development, and organogenesis.

Purpose: Understanding how FOXF2 influences the growth and development of cancer could provide valuable insights for researchers to develop novel therapeutic strategies.

Results: In this review, we investigate the underlying impact of FOXF2 on tumor cells, including the transformation of cellular phenotype, capacity for migration, invasion, and proliferation, colonization of circulating cells, and formation of metastatic nodules. In addition, we discuss the molecular mechanisms of FOXF2 in different cancers, including hepatocellular, esophageal, breast, colon, lung, prostate gland, as well as its role in embryonic development.

Conclusion: FOXF2 is a gene encoding a forkhead transcription factor belonging to the Forkhead Box family. The protein functions by recruiting activation transcription factors and basic components to activate the transcription of genes that interact with the complex. This review provides an in-depth analysis of the FOXF2's function and pleiotropic roles in cancer development and progression.

Background: Colorectal cancer (CRC) is the third most common cancer globally, with advanced stages presenting significant treatment challenges. Recently years, drug combination therapy has become a promising strategy for cancer treatment.

Objective: To evaluate the therapeutic efficacy of the combination of the anti-angiogenic drug PEP06 (TB01) and the cytotoxic drug Trifluridine/Tipiracil (TAS-102) in human CRC HCT-116 xenograft mouse model. And quantitative assessment of the interaction between TB01 and TAS-102 in the treatment based on pharmacological effects.

Methods: This study utilized the human CRC HCT-116 xenograft nude mouse model to evaluate the antitumor effects of TAS-102 and TB01, both as mono-therapies and in combination therapies.

Results: The combination therapy not only demonstrated significantly inhibited tumor growth in a dose-dependent manner, but also seems to reduce the common toxicity associated with such treatments, as shown by the maintenance of body weights in the treated mice.

Conclusion: The synergistic effect observed from the combined use of TAS-102 and TB01 suggests a promising new treatment avenue for refractory CRC patients, meriting further investigation and potential clinical application.

Purpose: Analysis of autofluorescence holds promise for brain tumor delineation and diagnosis. Therefore, we investigated the potential of a commercial confocal laser scanning endomicroscopy (CLE) system for clinical imaging of brain tumors.

Methods: A clinical CLE system with fiber probe and 488 nm laser excitation was used to acquire images of tissue autofluorescence. Fresh samples were obtained from routine surgeries (glioblastoma n = 6, meningioma n = 6, brain metastases n = 10, pituitary adenoma n = 2, non-tumor from surgery for the treatment of pharmacoresistant epilepsy n = 2). Additionally, in situ intraoperative label-free CLE was performed in three cases. The autofluorescence images were visually inspected for feature identification and quantification. For reference, tissue cryosections were prepared and further analyzed by label-free multiphoton microscopy and HE histology.

Results: Label-free CLE enabled the acquisition of autofluorescence images for all cases. Autofluorescent structures were assigned to the cytoplasmic compartment of cells, elastin fibers, psammoma bodies and blood vessels by comparison to references. Sparse punctuated autofluorescence was identified in most images across all cases, while dense punctuated autofluorescence was most frequent in glioblastomas. Autofluorescent cells were observed in higher abundancies in images of non-tumor samples. Diffuse autofluorescence, fibers and round fluorescent structures were predominantly found in tumor tissues.

Conclusion: Label-free CLE imaging through an approved clinical device was able to visualize the characteristic autofluorescence patterns of human brain tumors and non-tumor brain tissue ex vivo and in situ. Therefore, this approach offers the possibility to obtain intraoperative diagnostic information before resection, importantly independent of any kind of marker or label.