Cancer Management and Research最新文献

Background: Cholangiocarcinoma (CHOL) is a malignancy with poor clinical outcomes and limited treatment options. While extensive research has investigated genetic and signaling pathways in CHOL, the molecular mechanisms underlying disease pathogenesis remain incompletely understood. A key hurdle has been the lack of a systematic, multi-omic approach to illuminate causal relationships between genetic variants and CHOL risk.

Results: We integrated gene expression, co-expression network, and Mendelian randomization analyses to elucidate molecular drivers of CHOL. Gene set enrichment of differentially expressed genes from CHOL tumor samples identified enrichment in cancer-related biological processes. Weighted gene co-expression network analysis identified modules highly correlated with CHOL, including genes involved in cell cycle regulation, transcription, and proteolysis. Integrating these data with targets of the herbal formula Juhua, which shows anti-CHOL activity, pinpointed four candidate hub genes (CDK5, CDK7, CTSB, MAP2K2). Molecular docking revealed interactions between Juhua constituents and these hub genes. Mendelian randomization analysis of genetic variants implicated CCL2, CD5, CXCL6, CXCL9, HGF, IL10, IL10RA, IL18, IL24, IL2RB, IL6, IL8, SIRT2 and SLAMF1 as causally associated with CHOL.

Conclusion: Our multi-omic analysis provides new insight into molecular underpinnings of CHOL and identifies candidate disease drivers, signaling pathways and herbal targets for further validation. This systematic approach established a framework for illuminating causal links between genetics, molecular mechanisms and disease pathogenesis, with potential to accelerate drug and biomarker development for CHOL.

Background: Oral cancers, the eighth most common globally and sixth in Afghanistan, pose a major public health challenge due to limited healthcare access. Awareness is vital for prevention, control, and early detection.

Materials and methods: This cross-sectional study was conducted among university students in Kabul, Afghanistan, from April to November 2022. A revalidated questionnaire containing 14 closed-ended questions was translated into Dari by a specialist and distributed in person to students and dental interns, with an average completion time of approximately 10 min. The collected data were then analyzed using IBM SPSS version 25.

Results: The study included 178 males (39.3%) and 275 females (60.7%). About 74.6% identified smoking and tobacco chewing as causes of oral cancer, and 74.9% knew it is not transmitted through physical contact or speaking. Additionally, 60.9% believed oral cancer is curable. Males had a higher mean knowledge score (62.7%) compared to females (58.4%). More females had heard of oral cancer, but there were no significant gender differences in knowledge about causes, transmission, or the impact of AIDS on oral cancer.

Conclusion: The study revealed insufficient knowledge about oral cancer among participants. While males exhibited slightly better understanding than females, the difference was not significant.

Background: Cisplatin is a major chemotherapy drug in the treatment of Uterine Corpus Endometrial carcinoma (UCEC), and drug resistance often limits its efficacy. Studying the mechanism of cisplatin resistance in endometrial carcinoma is of great clinical importance. This study aims to analyze the expression and value of FANCD2 in UCEC.

Methods: The expression of FANCD2, prognosis, and relationship between FANCD2 and immune cell infiltration in UCEC were analyzed by using bioinformatics. The expression levels of FANCD2 in 62 cases of endometrial carcinoma and 28 cases of normal endometrial tissues were detected by RT-PCR, and the relationship between FANCD2 expression and clinicopathological features was analyzed. A FANCD2 knockdown plasmid was constructed and transfected into Ishikawa cells to detect the levels of GSH and MDA in the presence of different concentrations of cisplatin.

Results: Bioinformatics analysis showed that FANCD2 was highly expressed in UCEC tissues, and patients with high expression had poor prognosis. Immune infiltration analysis revealed that (B cell, CD8 T cell, macrophage, neutrophil, dendritic cell) infiltration was negatively correlated with FANCD2 expression. Compared with those in Ishikawa-Vector, the levels of GSH significantly decreased and those of MDA significantly increased in Ishikawa-FANCD2KD treated with different concentrations of cisplatin.

Conclusion: FANCD2 was highly expressed in UCEC, and the down-regulation of FANCD2 affected the levels of GSH and MDA to increase the cisplatin sensitivity of Ishikawa cells.

Waldenström macroglobulinemia (WM) is a relatively rare hematological malignancy characterized by serum monoclonal IgM gammopathy and bone marrow infiltration of lymphoma cells (small B lymphocytes, plasmacytoid lymphocytes, or plasma cells). Elevated CA125 is most seen in ovarian cancer or some benign diseases such as pelvic inflammatory disease and endometriosis. No cases of WM combined with elevated CA125 have been reported so far. Here, we report two rare cases of WM with abnormally high CA125 at the onset of illness. Patient 1 had a nine-year history of pulmonary shadow with a moderately increased CA125 level. Subsequently, she was diagnosed with WM-related lung involvement by biopsy. Patient 2 presented with WM manifestation and a significantly elevated CA125 level of unknown significance. Based on bone marrow smear results and serum IgM levels, the diagnosis of WM was established in both patients. After rigorous physical examination, imaging screening, and pathological biopsy, any underlying disease associated with elevated CA125 in both patients was excluded. CA125 and IgM levels decreased with effective treatment for WM, suggesting that abnormally elevated CA125 was related to the progression of macroglobulinemia. Suspicious WM patients with elevated serum CA125 of unknown significance need to be alert to a special manifestation of macroglobulinemia. More clinical concern is needed. At the same time, the clinician could monitor the patient's serum CA125 level changes to assist in the judgment of the efficacy of the original disease. This report extends the understanding of WM and the application of CA125.

Background: Liver cirrhosis (LC) is common among patients with esophageal squamous cell carcinoma (ESCC) due to shared etiologic factor, alcohol. For non-metastatic ESCC (nmESCC) patients with cirrhosis, surgery is often contraindicated or associated with high morbidity, therefore radiotherapy-based therapy was commonly applied. This study aims to investigate prognosticators for overall survival (OS) in nmESCC and cirrhotic patients receiving radiotherapy-based therapy. Furthermore, we will also evaluate the predictors for the 90-day mortality rate to reduce avoidable treatment-related toxic effects, and prevent medical waste.

Methods: Between January 2001 and December 2021, we retrospectively reviewed medical records of 1298 ESCC patients. Total 78 patients with nmESCC and liver cirrhosis identified based on abdominal ultrasonography, computerized tomography, or liver biopsy were enrolled. Clinicopathologic parameters were collected and correlated with OS and 90-day mortality.

Results: Univariate analysis revealed that Child-Pugh classification B/C (P<0.001, versus A), radiotherapy alone (P=0.03, versus chemoradiotherapy), prothrombin time (PT) prolonged≧2 seconds (P=0.024), albumin≦3.5g/dl (P<0.001), controlled/refractory ascites (P=0.01, versus none of ascites), and total bilirubin≧1.5mg/dl (P=0.004) were significantly associated with inferior OS. In multivariate analyses, albumin≦3.5g/dl (P=0.001, odds ratio (OR): 2.500) and total bilirubin≧1.5mg/dl (P=0.019, OR: 2.012) were independent adverse prognosticators. The 90-day mortality in these 78 patients receiving radiotherapy-based therapy was 10.3% (n=8), including ESCC progression in 4 patients, liver failure in 1 patient, and others in 3. Clinical 8th American Joint Committee on Cancer (AJCC) stage IVA (P=0.02), clinical T classification T3/4 (P=0.049), PT prolonged≧4 seconds (P=0.009), and albumin≦3.5g/dl (P=0.027) were significantly correlated with higher 90-day mortality. Logistic model showed albumin≦3.5g/dl (P=0.015, OR: 16.129) and clinical 8th AJCC stage IVA (P=0.012, OR: 17.544) were independently correlated with higher 90-day mortality.

Conclusion: Hypoalbuminemia is associated with higher 90-day mortality and poor prognosis in nmESCC and liver cirrhosis patients receiving radiotherapy-based therapy.

Introduction: This study aimed to compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in evaluating axillary lymph nodes (ALNs) status in breast cancer patients.

Methods: We retrospectively analyzed 590 female breast cancer patients who had undergone both ultrasound and MRI to assess ALNs prior to any invasive procedures. Using pathological results as the standard, we compared the diagnostic performance of the two imaging modalities.

Results: For differentiating between malignancy and benign ALNs, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound were 68.98%, 38.14%, 86.67%, 62.12% and 70.96%, respectively. MRI demonstrated corresponding values of 72.03%, 38.60%, 91.20%, 71.55% and 72.15%. In assessing the burden status of ALNs (high vs low), ultrasound yielded values of 78.47%, 52.75%, 83.17%, 36.36% and 90.61%, while MRI showed corresponding values of 81.19%, 52.75%, 86.37%, 41.38% and 90.93%. There were no statistically significant differences between the two imaging modalities in their ability to evaluate ALN malignancy or burden status.

Conclusion: Both ultrasound and MRI offer comparable value in assessing ALN status. Whether evaluating for metastatic involvement or determining ALN burden, it may not be necessary for patients to undergo both imaging tests.

Background: Globally, the disease that has the greatest impact on human health and is the most difficult to overcome is cancer (tumor or malignant tumor is another name for it). Cancers currently known to us can arise from almost any organ or tissue in the human body. Its uncontrolled growth pattern and metastasis characteristics are the fundamental reasons for the high mortality rate of cancer and its current incurability. An increasing number of studies have found that pyroptosis, a mode of programmed cell death, may inhibit tumor growth by changing the tumor immune microenvironment (TIME).

Methods: Through a retrospective study, we selected 160 cases of different tumor tissues (including 40 cases each of esophageal cancer, gastric cancer, breast cancer, and cervical cancer), and identified the expression of caspase3/GasderminE in the tumor tissues through immunohistochemical staining and infiltration of tumor-related immune cells. And analyze its relationship with clinical parameters of tumor patients. In addition, we also marked caspase8 and caspase9 among the caspase family members to analyze the main factors upstream of caspase3.

Results: The results showed that the expression level of caspase3/GSDME in different tumor tissues was positively correlated with the infiltration degree of tumor-related immune cells (natural killer cells, CD8+T cells, macrophages, etc). In addition, the expression level of caspase3 was positively correlated with caspase8, but not caspase9.

Summary: The expression levels of caspase3 and GSDME exhibited significant impacts on the survival prognosis of patients with diverse tumors as well as alterations in the immune microenvironment of tumor tissues, demonstrating statistical significance. After Caspase3/GSDME triggers the pyroptosis pathway, it may change the components of the immune microenvironment of tumor tissue, thereby achieving the effect of inhibiting tumors.

Purpose: The value of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT), in predicting the prognosis of intrahepatic cholangiocarcinoma (ICC) patients who underwent curative resection has not been elucidated. Therefore, we aimed to construct prognostic nomograms for surgically treated ICC patients.

Methods: The impact of liver enzymes on overall survival (OS) and recurrence-free survival (RFS) was analysed using Kaplan-Meier analysis and evaluated by univariate and multivariate analyses. Nomograms were constructed for predicting the probability of 1-, 3-, and 5-year OS and RFS and evaluated by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA).

Results: High ALT, AST, ALP and GGT levels were associated with worse prognoses in surgically treated ICC patients. Nomograms for OS and RFS were constructed based on five prognostic factors: number of high liver enzyme (No. HLE), CA19-9 ≥ 37 U/mL, multiple tumours, lymph node invasion and microvascular invasion (MVI). Compared with 8th edition TNM stage, these nomograms showed better predictive value. The C-index and 1-, 3- and 5-year areas under the curve (AUCs) of the nomograms for OS and RFS in the discovery and validation cohorts were higher than those of the 8th TNM stage. The calibration plots indicated that there was good agreement between the actual observations and predictions.

Conclusion: Preoperative ALT, AST, ALP and GGT levels could predict prognosis in surgically treated ICC patients. The nomograms showed good predictive ability for predicting the survival of ICC patients.

Background: Existing research shows inducing ferroptosis can improve the effectiveness of tumor treatment. Glutathione peroxidase 4 (GPX4) is a ferroptosis inhibitor. Solute carrier family 7, membrane 11 (SLC7A11) plays a key role in glutathione homeostasis, which is important for protecting cells from oxidative stress. β-catenin is the key protein the Wnt/β-catenin signaling pathway. The purpose of this study was to investigate the expression of SLC7A11 and GPX4 in colorectal cancer (CRC) and their relationship with β-catenin and to analyze the association of these two factors with several clinicopathological features and patient survival.

Methods: This study retrospectively collected paraffin-embedded tissue samples from 120 CRC patients, who received surgical resection between 2017 and 2018. We examined the patterns of expression of SLC7A11, GPX4 and β-catenin by using immunohistochemistry. Analyzing the relationships between SLC7A11, GPX4, β-catenin and clinical pathological parameters and their relationships with overall survival (OS).

Results: Expression of SLC7A11 and GPX4 were high expression in 60.83% and 64.17% among the patients, respectively, and were higher than those in normal tissue. SLC7A11, GPX4 and β-catenin were positively correlated with each other (P<0.05). Expression of SLC7A11 and GPX4 significantly correlates with tumor stage and lymph node metastasis (P < 0.05). The β-catenin was related to lymph node metastasis, TNM stage and tumor grade. Kaplan-Meier analysis showed that patient's OS in the SLC7A11 and GPX4 were reduced (P<0.05). Univariate and multivariate analyses showed that SLC7A11 and GPX4 were independent risk factors for CRC prognosis.

Conclusion: SLC7A11 and GPX4 overexpression is associated with β-catenin and poor prognosis and may be important for predicting CRC invasion, metastasis, and prognosis.

Background: The associations of metabolic conditions, chronic organ dysfunctions and acidic food consumption with the risk of gastrointestinal cancer are unknown among individuals with primary hypertension. We sought to identify risk factors for gastrointestinal cancer in this population.

Methods: We conducted a case-control study among individuals who had primary hypertension and were later diagnosed with a type of gastrointestinal cancer, and those who had primary hypertension and were not diagnosed with gastrointestinal cancer at a local hospital from January 2020 to January 2024. We compared sociodemographic, lifestyle, dietary, and medical characteristics between the groups using data extracted from electronic medical records. Univariate and multivariate logistic regression were used to find associations with risk factors.

Results: We identified 125 cases of gastrointestinal cancer and 544 controls who were cancer-free. There were significant associations between overall gastrointestinal cancer and hyperlipidemia (OR, 3.37; 95% CI, 1.98-5.72), diabetes mellitus (OR, 2.58; 95% CI, 1.64-4.07), chronic renal failure (OR, 2.45; 95% CI, 1.43-4.20), alcohol consumption (OR, 2.35; 95% CI, 1.49-3.70), heart failure (OR, 2.13; 95% CI, 1.36-3.33), and higher-grade hypertension (OR, 1.97; 95% CI, 1.41-2.74).

Conclusion: In this retrospective study of patients who had primary hypertension, we identified several comorbid conditions as indicators for gastrointestinal cancer, including hyperlipidemia, diabetes mellitus, chronic renal failure, alcohol consumption, heart failure, and higher-grade hypertension.