Background
Multiparametric intravoxel incoherent motion (IVIM) provides diffusion and perfusion information for the treatment prediction of cancer. However, the superiority of IVIM over dynamic ...contrast‐enhanced (DCE) magnetic resonance imaging (MRI) in locally advanced hypopharyngeal carcinoma (LAHC) remains unclear.
Purpose
To compare the diagnostic performance of IVIM and model‐free DCE in assessing induction chemotherapy (IC) response in patients with LAHC.
Study Type
Prospective.
Population
Forty‐two patients with LAHC.
Field Strength/Sequence
3.0 T MRI, including IVIM (12 b values, 0–800 seconds/mm2) with a single‐shot echo planar imaging sequence and DCE‐MRI with a volumetric interpolated breath‐hold examination sequence. IVIM MRI is a commercially available sequence and software for calculation and analysis from vendor.
Assessment
The IVIM‐derived parameters (diffusion coefficient D, pseudodiffusion coefficient D*, and perfusion fraction f) and DCE‐derived model‐free parameters (Wash‐in, time to maximum enhancement Tmax, maximum enhancement Emax, area under enhancement curve AUC over 60 seconds AUC60, and whole area under enhancement curve AUCw) were measured. At the end of IC, patients with complete or partial response were classified as responders according to the Response Evaluation Criteria in Solid Tumors.
Statistical Tests
The differences of parameters between responders and nonresponders were assessed using Mann–Whitney U tests. The performance of parameters for predicting IC response was evaluated by the receiver operating characteristic curves.
Results
Twenty‐three (54.8%) patients were classified as responders. Compared with nonresponders, the perfusion parameters D*, f, f × D*, and AUCw were significantly higher whereas Wash‐in was lower in responders (all P‐values <0.05). The f × D* outperformed other parameters, with an AUC of 0.84 (95% confidence interval CI: 0.69–0.93), sensitivity of 79.0% (95% CI: 54.4–93.9), and specificity of 82.6% (95% CI: 61.2–95.0).
Data Conclusion
The IVIM MRI technique may noninvasively help predict the IC response before treatment in patients with LAHC.
Level of Evidence
2
Technical Efficacy
Stage 2
Background: Microsatellite instability (MSI) is associated with treatment response and prognosis in patients with rectal cancer (RC). However, intratumoral heterogeneity limits MSI testing in ...patients with RC. We developed a subregion radiomics model based on multiparametric magnetic resonance imaging (MRI) to preoperatively assess high-risk subregions with MSI and predict the MSI status of patients with RC. Methods: This retrospective study included 475 patients (training cohort, 382; external test cohort, 93) with RC from two participating hospitals between April 2017 and June 2023. In the training cohort, subregion radiomic features were extracted from multiparametric MRI, which included T2-weighted, T1-weighted, diffusion-weighted, and contrast-enhanced T1-weighted imaging. MSI-related subregion radiomic features, classical radiomic features, and clinicoradiological variables were gathered to build five predictive models using logistic regression. Kaplan–Meier survival analysis was conducted to explore the prognostic information. Results: Among the 475 patients (median age, 64 years interquartile range, IQR: 55–70 years;304 men and 171 women), the prevalence of MSI was 11.16% (53/475). The subregion radiomics model outperformed the classical radiomics and clinicoradiological models in both training (area under the curve AUC=0.86, 0.72, and 0.59, respectively) and external test cohorts (AUC=0.83, 0.73, and 0.62, respectively). The subregion-clinicoradiological model combining clinicoradiological variables and subregion radiomic features performed the optimal, with AUCs of 0.87 and 0.85 in the training and external test cohorts, respectively. The 3-year disease-free survival rate of MSI groups predicted based on the model was higher than that of the predicted microsatellite stability (MSS) groups in both patient cohorts (training, P =0.032; external test, P =0.046). Conclusions: We developed and validated a model based on subregion radiomic features of multiparametric MRI to evaluate high-risk subregions with MSI and predict the MSI status of RC preoperatively, which may assist in individualized treatment decisions and positioning for biopsy.
Breast cancer remains a leading cause of mortality in women worldwide. Triple-negative breast cancer (TNBC) is a particularly aggressive subtype characterized by rapid progression, poor prognosis, ...and lack of clear therapeutic targets. In the clinic, delineation of tumor heterogeneity and development of effective drugs continue to pose considerable challenges. Within the scope of our study, high heterogeneity inherent to breast cancer was uncovered based on the landscape constructed from both tumor and healthy breast tissue samples. Notably, TNBC exhibited significant specificity regarding cell proliferation, differentiation, and disease progression. Significant associations between tumor grade, prognosis, and TNBC oncogenes were established via pseudotime trajectory analysis. Consequently, we further performed comprehensive characterization of the TNBC microenvironment. A crucial epithelial subcluster, E8, was identified as highly malignant and strongly associated with tumor cell proliferation in TNBC. Additionally, epithelial-mesenchymal transition-associated fibroblast and M2 macrophage subclusters exerted an influence on E8 through cellular interactions, contributing to tumor growth. Characteristic genes in these three cluster cells could therefore serve as potential therapeutic targets for TNBC. The collective findings provided valuable insights that assisted in the screening of a series of therapeutic drugs, such as pelitinib. We further confirmed the anti-cancer effect of pelitinib in an orthotopic 4T1 tumor-bearing mouse model. Overall, our study sheds light on the unique characteristics of TNBC at single-cell resolution and the crucial cell types associated with tumor cell proliferation that may serve as potent tools in the development of effective anti-cancer drugs.
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•A common cluster of proliferating malignant epitheliums was identified in TNBC.•TPX2, CDCA8, PLK1, UBE2S, RRM2, and TK1 are TNBC independent risk factors.•EMT fibroblast and M2 macrophage promote aforementioned proliferating malignant epitheliums for tumor growth in TNBC.•Drugs like pelitinib inhibit TNBC by suppressing multiple cell clusters in tumor microenvironment.
Breast cancer (BC) is the most prevalent malignancy among women worldwide. Mounting evidence suggests that PANoptosis participates in cancer development and therapy. However, the role of PANoptosis ...in BC remains unclear. In this study, we identified ten PANoptosis-related genes using Cox regression analysis, random forest (RF) algorithm and least absolute shrinkage and selection operator (LASSO) algorithm. A PANoptosis-related score (PRS) was calculated based on the coefficient of LASSO. Notably, we divided the patients into high- and low-risk groups according to the PRS and revealed a negative correlation between PRS and overall survival. Next, a nomogram model was constructed and validated to improve the clinical application of PRS. Functional enrichment analyses and the Bayesian network demonstrated that differentially expressed genes between high- and low-risk groups were mainly enriched in immune-related pathways. Besides, we found significant differences in tumor mutation burden and tumor immune microenvironment between patients in these two groups using bulk-RNA and single-cell RNA sequencing data. Furthermore, charged multivesicular body protein 2B (CHMP2B) was identified as the hub gene by combining LASSO, weighted gene co-expression network analysis, RF and eXtreme Gradient Boosting. Importantly, using immunohistochemistry analysis based on our tissue microarray, we found that CHMP2B was highly expressed in tumor tissue, and CD4 and CD8 were more likely to be positive in the CHMP2B-negative group. Survival analyses revealed that CHMP2B adversely impacted the survival of BC patients. In conclusion, we not only constructed a highly accurate predictive model based on PRS, but also revealed the importance of PANoptosis-related gene signature in the modulation of the tumor microenvironment and drug sensitivity in BC.
Programmed cell death 4 (PDCD4) is a novel tumor suppressor gene and a promising target for anticancer therapies. PDCD4 is frequently downregulated in various human cancers; however, the molecular ...mechanism accounting for the loss expression of PDCD4 in cancers is not fully understood. In this study, we identified specific targeting sites for miR-208a-3p in the 3'-untranslated region (3'-UTR) of the PDCD4 gene which regulated PDCD4 expression. We demonstrated that miR-208a-3p suppressed apoptosis in gastric cancer cells by targeting PDCD4. We also showed that miR-208a-3p promoted the development of tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, this study revealed a critical role for miR-208a-3p as an oncogenic miRNA in gastric carcinogenesis and it may provide a potential novel target for gastric cancer diagnosis and therapy.
Background
Guideline recommendations for the application of neoadjuvant chemotherapy (NACT) in T2N1M0 stage hormone receptor-positive, HER2-negative (HR + /HER2-) breast cancer are ambiguous. The ...debate continues regarding whether NACT or adjuvant chemotherapy (ACT) offers superior survival outcomes for these patients.
Materials and Methods
Female patients diagnosed with HR + /HER2- breast cancer at T2N1M0 stage between 2010 and 2020, were identified from the Surveillance, Epidemiology, and End Results database and divided into two groups, the NACT group and the ACT group. Propensity score matching (PSM) was utilized to establish balanced cohorts between groups, considering baseline features. Kaplan–Meier (K-M) analysis and the Cox proportional hazards model were executed to assess the efficacy of both NACT and ACT in terms of overall survival (OS) and breast cancer-specific survival (BCSS). A logistic regression model was employed to examine the association between predictive variables and response to NACT.
Results
After PSM, 4,682 patients were finally included. K-M curves showed that patients receiving NACT exhibited significantly worse OS and BCSS when compared with patients undergoing ACT. Multivariable Cox analysis indicated that not achieving pathologic complete response (non-pCR) after NACT (versus ACT), was identified as an adverse prognostic factor for OS (HR 1.58, 95% CI 1.36–1.83) and BCSS (HR 1.70, 95% CI 1.44–2. 02). The logistic regression model revealed that low tumor grade independently predicted non-pCR.
Conclusion
Among T2N1M0 stage HR + /HER2- patients, OS and BCSS of NACT were inferior to ACT. Patients who attained non-pCR after NACT demonstrated significantly worse survival outcomes compared with those who received ACT.
Background. Emerging studies have revealed long noncoding RNAs (lncRNAs) were key regulators of cancer progression. In this research, the expression and roles of MBNL1-AS1 were explored in breast ...cancer (BC). Methods. In this study, the MBNL1-AS1 expression in breast cancer tissue, as well as in cell line, was studied by qRT-PCR assays. The effects of MBNL1-AS1 on proliferation and stemness were evaluated by MTT assays, colony formation assays, orthotopic breast tumor mice models, extreme limiting dilution analysis (ELDA), fluorescence in situ hybridization (FISH), flow cytometry assays, and sphere formation assays. Flexmap 3D assays were performed to show that MBNL1-AS1 downregulated the centromere protein A (CENPA) secretion in BC cells. Western blot, RNA pull-down assays, RNA immunoprecipitation (RIP) assays, and FISH were conducted to detect the mechanism. Results. The results showed that the expression levels of MBNL1-AS1 were downregulated in breast cancer tissues and cell lines. In vitro and in vivo studies demonstrated that overexpression of MBNL1-AS1 markedly inhibited BC cells proliferation and stemness. RNA pull-down assay, RIP assay, western blot assay, and qRT-PCR assay showed that MBNL1-AS1 downregulated CENPA mRNA via directly interacting with Zinc Finger Protein 36 (ZFP36) and subsequently decreased the stability of CENPA mRNA. Restoration assays also confirmed that MBNL1-AS1 suppressed the CENPA-mediated proliferation and stemness in breast cancer cells. Conclusions. The new mechanism of how MBNL1-AS1 regulates BC phenotype is elucidated, and the MBNL1-AS1/ZFP36/CENPA axis may be served as a therapeutic target for BC patients.
BRCA1-associated protein-1 (BAP1) is an important nuclear-localized deubiquitinating enzyme that serves as a tumor suppressor in lung cancer; however, its function and its regulation are largely ...unknown. In this study, we found that BAP1 protein levels were dramatically diminished in lung cancer tissues while its mRNA levels did not differ significantly, suggesting that a post-transcriptional mechanism was involved in BAP1 regulation. Because microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for miRNAs that could potentially bind BAP1. We predicted and experimentally validated miR-31 as a direct regulator of BAP1. Moreover, we showed that miR-31 promoted proliferation and suppressed apoptosis in lung cancer cells and accelerated the development of tumor growth in xenograft mice by inhibiting BAP1. Taken together, this study highlights an important role for miR-31 in the suppression of BAP1 in lung cancer cells and may provide insights into the molecular mechanisms of lung carcinogenesis.
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