• AKR1B1 and AKR1B10 as Potential Prognostic Biomarkers of Endometrial Cancer.
    2 weeks ago
    Endometrial cancer (EC) is the most common gynecological malignancy with rising incidence, yet reliable non-invasive prognostic biomarkers for preoperative risk stratification and treatment guidance are needed. This pilot study investigated whether plasma levels of aldo-keto reductase family 1 member B1 (AKR1B1) and aldo-keto reductase family 1 member B10 (AKR1B10) could serve as non-invasive prognostic biomarkers in EC. Plasma samples were collected preoperatively from 78 postmenopausal women with histologically confirmed EC alongside clinicopathological data including histological grade, depth of myometrial invasion, lymphovascular invasion, and metastatic status. AKR1B1 and AKR1B10 protein levels were quantified using enzyme-linked immunosorbent assays (ELISAs) in 72 and 64 plasma samples, respectively, and data were analyzed using R v4.3.0. Plasma AKR1B10 levels were significantly higher in Grade 3 compared to Grade 1-2 EC patients; and should be considered with caution given the limited Grade 3 sample size. A model combining both AKR1B1 and AKR1B10 with clinical variables (BMI, age, smoking, parity, hormone replacement therapy, previous use of contraceptives) showed limited discriminative ability for preoperative lymphovascular invasion prediction and is not suitable for clinical use in its current form. Survival analysis revealed that patients with plasma levels of both AKR1B1 and AKR1B10 below the median showed significantly better overall (p = 0.04, hazard ratio (HR) = 0.33, 95% confidence interval (CI): 0.10-1.01) and recurrence-free survival (p = 0.005, HR = 0.09, 95% CI: 0.02-0.49) compared to the remainder of the cohort. These preliminary, hypothesis-generating findings suggest the potential of circulating AKR1B proteins as candidate prognostic biomarkers in EC, requiring prospective validation in larger cohorts.
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  • Long Noncoding RNAs (lncRNAs) as Biomarkers of Prognosis in TNBC and Non-TNBC Breast Cancer Patients.
    2 weeks ago
    Functional studies have shown that long noncoding RNAs (lncRNAs) play different roles in gene expression regulation, acting as epigenetic factors. Accumulating evidence indicates that lncRNAs modulate diverse biological processes, and their altered expression is associated with the development and progression of cancer, including BC. Here, aiming to identify lncRNAs associated with breast cancer, we performed a re-analysis of the expression data from 1071 tumors of eligible patients in the LACRN-MPBC Study. Using normalized data, we compared the expression profiles of triple-negative breast cancer (TNBC; 170 cases) and a heterogeneous group of non-TNBC tumors (782 cases). A total of 59 differentially expressed lncRNAs (DELncRNAs) could be identified based on the criteria of |log2FC| ≥ 1 and FDR < 0.05, using the DESeq2 R package. In the Kaplan-Meier survival analysis, we identified DELncRNAs that affect disease-free survival and/or overall survival, with eight of them in TNBC and 27 in non-TNBC patients. Multivariate Cox proportional-hazards models were used to evaluate independent predictors of survival. Two DELncRNAs, VLDLR-AS1 and PART1, were identified as independent prognostic markers for TNBC patients, while seven (LINC00239, FAM30A, LINC00842, LINC01315, EGOT, LY6E-DT, and SLC25A21-AS1) were independent prognostic markers for non-TNBC patients. Our computational study identifies several candidate lncRNAs associated with clinical outcomes in breast cancer. However, the DELncRNAs identified here should be interpreted as preliminary candidates, which require future validation and functional studies to determine their biological roles and evaluate their potential as prognostic biomarkers.
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  • Protein Profiling Identifies Biomarkers for Predicting Disease Severity in Anti-NMDAR Encephalitis.
    2 weeks ago
    Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neurological disorder characterized by pathogenic antibodies against the NMDAR. A systematic protein profiling approach is warranted to identify biomarkers capable of predicting disease status. An Olink proximity extension assay (PEA) profiled 91 inflammation-related proteins from anti-NMDAR encephalitis patients. Disease severity or prognosis were assessed by CASE score or mRS score at 6-month follow-up. Patients were stratified into distinct molecular clusters using unsupervised clustering. Logistic regression models incorporating selected biomarkers were developed to predict disease severity and prognosis, followed by absolute quantification using ELISA. Patients were classified into four consensus clusters. Clusters 1 and 2 corresponded to the mild group, while Cluster 3 represented the severe group, consistent with CASE score above 6. Cluster 4 showed heterogeneous clinical features. Elevated serum levels of IL-10, IL-6, and SIRT2, as well as increased CSF levels of CXCL10, CXCL11, and MMP10, were positively associated with severe disease. Conversely, several proteins including LTA and CCL11, CCL8, TGFB1, CXCL6 were associated with severe disease or unfavorable 6-month outcomes. A logistic regression model combining serum CXCL6 and CCL11 with CSF MMP10 achieved an area under the curve (AUC) of 0.95 for predicting disease severity. Serum CCL11 alone showed predictive value for 6-month prognosis, with an AUC of 0.79. These findings delineate distinct protein signatures associated with clinical heterogeneity of anti-NMDAR encephalitis. Prediction models incorporating multiple biomarkers may provide an approach for disease severity stratification and prognosis forecast.
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  • Successful treatment of massive stage IIIB cervical cancer with a spindle cell component: A case report.
    2 weeks ago
    Cervical cancer is one of the most common malignancies in women worldwide. Tumors larger than 10 cm in diameter are rarely encountered, and no standard protocol exists for treating them. This case serves as a reference for managing similarly giant tumors and illustrates how a sequential multimodal strategy can downstage the disease.

    A 33-year-old woman presented with a cervical mass of 14 × 13 × 13 cm, 6 months of intermittent vaginal bleeding, and 1 month of progressive fatigue.

    Biopsy confirmed stage IIIB cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics 2021) with a partial spindle cell component.

    Because of the tumor size, neoadjuvant chemotherapy was given first to reduce tumor burden; concurrent chemoradiotherapy and bevacizumab were then administered.

    Complete remission was achieved after the planned treatment sequence. Imaging at 6 months of follow-up showed no recurrence or metastasis.

    Individualized sequential multimodal therapy can produce complete remission in massive cervical squamous cell carcinoma. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy plus bevacizumab may be a curative option for selected patients with bulky stage IIIB disease.
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  • Clinical outcomes associated with GLP-1 receptor agonist use in metabolic dysfunction-associated steatohepatitis: A multinational cohort study.
    2 weeks ago
    Metabolic dysfunction-associated steatohepatitis (MASH) is an important progressive liver disorder that can lead to hepatic decompensation, hepatocellular carcinoma (HCC), and premature death. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated beneficial effects on metabolic dysfunction and liver histology; however, their relationship with major long-term hepatic outcomes in routine clinical practice has not been fully established. A retrospective multicenter cohort study was conducted using a large real-world health database. Adults with MASH were classified according to whether they had documented exposure to GLP-1 RAs. The 2 groups were balanced using 1:1 propensity score matching based on demographic variables, coexisting conditions, and concomitant therapies. The outcomes evaluated were ascites, HCC, and all-cause mortality, with comparative effects reported as risk differences (RDs) and 95% confidence intervals (CIs). The initial study population comprised 1434,086 individuals with MASH, including 168,740 GLP-1 RA users and 1265,346 individuals without GLP-1 RA exposure. After matching, 168,733 patients were retained in each cohort with comparable baseline characteristics. Exposure to GLP-1 RAs was associated with fewer cases of ascites (RD - 0.013; 95% CI - 0.014 to - 0.012; P < .001) and lower all-cause mortality (RD - 0.022; 95% CI - 0.023- - 0.021; P < .001). A statistically significant increase in HCC incidence was observed among GLP-1 RA users; however, the magnitude of the absolute difference was minimal (RD 0.000; 95% CI 0.000-0.001; P = .025). Among patients with MASH, GLP-1 RA exposure was associated with a lower incidence of ascites and reduced mortality in this large real-world matched cohort. While a statistically significant difference in HCC occurrence was detected, its negligible absolute magnitude suggests limited clinical relevance. These findings support the potential role of GLP-1 RAs as beneficial and hepatically safe therapies in patients with MASH.
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  • Subtype-dependent prognostic significance of Ki-67, histological grade, and vascular invasion in breast and colorectal cancer.
    2 weeks ago
    Traditional pathological markers remain relevant in prognostic assessment for solid tumors, but their clinical value may differ according to tumor biological context. This study evaluated the prognostic significance of Ki-67, histological grade, and vascular invasion (VI) in breast and colorectal cancer, with emphasis on subtype-specific differences. This single-center retrospective cohort included 846 patients with breast cancer or colorectal cancer who underwent curative-intent surgery between 2015 and 2022. Ki-67 expression, histological grade, and VI were extracted from pathological records. The pooled analysis was designed as an exploratory cross-cancer comparison of shared pathological features rather than as an assumption of biological equivalence between the 2 malignancies; cancer-specific and molecular-context analyses were therefore emphasized. Overall survival was assessed using Cox proportional hazards regression, with subgroup analyses according to breast cancer surrogate molecular subtype and colorectal cancer mismatch repair status. A simple Ki-67/VI score was explored for risk stratification. In multivariable analysis, increased age, stage III disease, high Ki-67 expression, and VI were independently associated with worse overall survival, whereas histological grade was not retained as an independent predictor. In breast cancer, the prognostic effect of Ki-67 was evident in luminal B and triple-negative subtypes but not in luminal A disease. In colorectal cancer, VI showed stronger prognostic value in proficient mismatch repair tumors than in deficient mismatch repair tumors. The combined Ki-67/VI score provided incremental prognostic stratification and showed better discriminatory performance than any single marker alone. Ki-67 and VI were associated with prognosis in this retrospective cohort, and the magnitude of these associations varied according to tumor biological context. The Ki-67/VI score should be regarded as exploratory and hypothesis-generating pending internal optimism correction and external validation. Interpretation of conventional pathological indicators should therefore remain cancer- and subtype-specific.
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  • Risk factors for intraoperative adhesion in ovarian endometriosis patients: A retrospective study.
    2 weeks ago
    Endometriosis is a common gynecological disease that can cause pelvic adhesions. Severe adhesions increase the difficulty of surgery, resulting in prolonged operation time, increased intraoperative bleeding, and increased complications such as surgical injury. Preoperative preparation can be improved if the severity of adhesions in a patient can be predicted. This study aimed to identify independent risk factors for moderate-to-severe pelvic adhesions in patients with ovarian endometriosis and evaluate the predictive performance of routine preoperative clinical and laboratory parameters for adhesion severity. A retrospective review of the medical records at our hospital was conducted to identify patients with ovarian endometriosis confirmed by pathology between January 2018 and September 2024. We collected data on age, presence of dysmenorrhea or chronic pelvic pain, location and size of ovarian cysts, routine blood tests, coagulation tests, and tumor marker tests. The patients were categorized into the no or mild adhesion group and the moderate-to-severe adhesion group based on the modified American Society for Reproductive Medicine scoring system. In this study, 128 patients were included in the no or mild adhesion group, whereas 186 patients were included in the moderate-to-severe adhesion group. There were no significant differences in body mass index size, or pain symptoms between the 2 groups. However, age, cyst location, and revised American Fertility Society stage were significantly different. When comparing routine blood tests, coagulation tests, and tumor marker tests, we found that the levels of neutrophil-to-lymphocyte ratio, cancer antigen 125 (CA125), cancer antigen 19-9 (CA19-9), and fibrinogen (FIB) were significantly higher in the moderate-to-severe adhesion group than in the group with no or mild adhesion (P < .05). The multivariate logistic regression analysis revealed that location, age, and FIB status were independent risk factors for ovarian endometriosis. Advanced age, bilateral ovarian cysts, and elevated preoperative FIB levels are independent risk factors for moderate-to-severe pelvic adhesions in patients with ovarian endometriosis.
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  • Recurrence score prediction formula based on immunohistochemistry and biopsy data to predict response to neoadjuvant chemotherapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer: A retrospective cohort study.
    2 weeks ago
    Oncotype DX® is a validated 21-gene tool for assessing survival benefits of adjuvant chemotherapy for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer, but its use in core biopsy specimens is limited by costs, access issues, and available tissue volumes, highlighting the need for an alternative to Oncotype DX®. Therefore, we developed a recurrence score (RS) prediction formula and investigated whether the RS-predicted value calculated from biopsy material could predict pathological complete responses (pCRs) from neoadjuvant chemotherapy (NAC). This retrospective cohort study examined consecutive patients with ER+/HER2- primary breast cancer who underwent surgery after NAC at Kitasato Institute Hospital between 2012 and 2023. These values were matched with histological responses to chemotherapy and other clinical and pathological factors. Among 61 patients (median age 54 years), 50% had clinical tumor status 2 tumors, and 40% had node-positive disease. Six patients (9.8%) achieved pCRs, whereas 55 (90.2%) did not. The median RS-predicted value was significantly higher in the pCR group (38.6) than in the non-pCR group (14.0). The pCR rates were 3.8% (2/53 cases) for RS-predicted values < 26 and 50.0% (4/8 cases) for RS-predicted values ≥ 26. The optimal RS-predicted cutoff value for predicting pCRs was 33.785, with a sensitivity of 66.7% and a specificity of 98.2%. Higher RS-predicted values calculated from routinely available biopsy biomarkers were associated with a greater likelihood of pCR after NAC in patients with ER+/HER2- breast cancer. These preliminary findings suggest that the RS-predicted value may have potential as an accessible tool for predicting the chemotherapy response; however, validation in larger independent cohorts and direct comparisons with the actual Oncotype DX® RS are warranted.
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  • Efficacy of HALP combined with T2-weighted MRI radiomics in predicting pathological complete response and overall survival in rectal cancer after neoadjuvant chemoradiotherapy: A retrospective single-center study in China.
    2 weeks ago
    This study aimed to develop and validate an integrated model combining pretreatment hemoglobin, albumin, lymphocyte, platelet (HALP) score and T2-weighted magnetic resonance imaging radiomics for predicting pathological complete response (pCR) and overall survival in patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant chemoradiotherapy. A total of 137 consecutive LARC patients from January 2019 to January 2022 were retrospectively included. Pretreatment 3.0T T2-weighted high-resolution magnetic resonance imaging scans were performed. Four stable features were selected using least absolute shrinkage and selection operator regression. The HALP score was calculated as (hemoglobin × albumin × lymphocytes)/platelets, with an optimal cutoff of 48.4 determined by X-tile analysis. Three predictive models were constructed: a radiomics-only model (RAD), a HALP-only model (HALP), and a combined model (RAD + HALP) using a random forest classifier. Model performance was assessed using the area under the curve (AUC), sensitivity, specificity, calibration curves, and decision curve analysis. The pCR rate was 13.1% (18/137). For pCR prediction, the combined model achieved an AUC of 0.808 (95% confidence interval: 0.73-0.88), compared to 0.788 for the RAD model. The HALP score alone did not show predictive capability (P = .59). For overall survival prediction, the combined model significantly outperformed the individual models, with an AUC of 0.957 (sensitivity: 0.945, specificity: 1.0; DeLong test, P = .002), the AUC was corrected to 0.852 (sensitivity: 0.788, specificity: 0.889; P < .001). Multivariate Cox analysis identified HALP as an independent prognostic factor (hazard ratio: 5.83, 95% confidence interval: 2.23-15.2). The combined RAD + HALP model demonstrated excellent and internally validated performance in predicting both short-term treatment response and long-term survival in LARC patients undergoing neoadjuvant chemoradiotherapy patients. Prospective multicenter studies are warranted prior to clinical application.
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  • Successful treatment of a large-sized triple-negative breast cancer: A case report.
    2 weeks ago
    Triple-negative breast cancer (TNBC) is defined as the absence of estrogen receptor and progesterone receptor expression, along with a lack of human epidermal growth factor receptor 2 overexpression or amplification. Patients with TNBC exhibit a poorer prognosis, characterized by a higher propensity for metastasis to the lungs, liver, and brain, and a lower overall survival rate than other breast cancer subtypes. Primary treatment modalities for TNBC include surgery, chemotherapy, and radiotherapy. Although stereotactic body radiotherapy (SBRT) has been reported for the treatment, there is a paucity of comprehensive research in this field.

    We report a case of successful treatment of a 38-year-old female patient with TNBC who experienced recurrence after surgery. The tumor occurred 1 year after surgery. The tumor showed rapid progression and growth.

    Stage Ⅳ TNBC with lung metastasis.

    After visiting multiple hospitals, the patient finally underwent SBRT combined with chemotherapy. During SBRT implementation, an ultrahigh-dose radiotherapy modality was adopted, which is a rarely reported approach in previous studies. Subsequently, a conventional fractionated radiotherapy regimen was administered. Concurrent with radiotherapy, the patient received 2 cycles of chemotherapy.

    The patient's tumor shrank rapidly, with minimal adverse reactions. Nine months later, the tumor remained well controlled.

    Treatment of TNBC remains challenging. Given the aggressive progression of the tumor, a new radiotherapy regimen was adopted. Given that such an approach has scarcely been documented in the published literature, this case may offer novel implications for clinical practitioners.
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