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PURPOSE: Dyadic communication positively affects marital relationships, good relationships help restore body image, and this study explores the relationship between dyadic communication and body image of breast cancer patients. METHODS: Cross-sectional correlation design with convenience sampling was used to recruit participants from two outpatient medical centers. Demographic information, medical records, and two questionnaires, dyadic communicative resilience scale (DCRS) and body image scale (BIS), were administered. Participants comprised women with breast cancer and their partners. Multiple regression analysis was performed to control related factors to understand the association between the DCRS of the women with breast cancer and their partners and the women's body image. Analysis of variance (ANOVA) was performed to analyze between three categories of couple's communication status (consistent and good, consistent and poor, and inconsistent) and body image of women with breast cancer. RESULTS: Data were obtained from 162 women with breast cancer and 90 partners. The study found (1) significant correlation between the women's perception of their communication and body image, (2) humor in partner's perception of their communication was significantly associated with women's body image, and (3) dyadic communication that both patients and partners were consistent and good in the domain of keeping pre-cancer routines and attractiveness was associated with women's body image. CONCLUSION: The correlation between dyadic communication and the body image of women with breast cancer is significant. Improving communication specific on keeping pre-cancer routines and attractiveness between women with breast cancer and their partners could enhance the women's body image.
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Imagen Corporal , Neoplasias de la Mama , Comunicación , Humanos , Femenino , Neoplasias de la Mama/psicología , Imagen Corporal/psicología , Estudios Transversales , Persona de Mediana Edad , Adulto , Encuestas y Cuestionarios , Esposos/psicología , Relaciones Interpersonales , Masculino , Anciano , Análisis de Regresión , Análisis de Varianza , Resiliencia PsicológicaRESUMEN
This research investigated the anticancer properties of punicalagin, a prominent bioactive polyphenol extracted from Punica granatum L, in human gastric cancer cell lines. Normal and gastric cancer cells were exposed to different doses of punicalagin for various durations. Punicalagin exhibited cytotoxic effects on gastric cancer cells in a dose- and time-dependent fashion, while sparing normal gastric epithelial cells. It is noteworthy that among the 3 gastric cancer cells, HGC-27 cells were more resistant to punicalagin than 23,132/87 and AGS cells. Furthermore, punicalagin triggered apoptosis in gastric cancer cells, evidenced by a rise in both early and late apoptotic cell percentages. Western blot analysis further revealed that punicalagin elevated the levels of activated caspase-3. Conversely, punicalagin curtailed cell invasion and reduced the expression of MMP-2, MMP-9, Snail, and Slug. From a mechanistic standpoint, Western blotting indicated that punicalagin might inhibit the Erk and NF-κB pathways, leading to apoptosis induction and the inhibition of cell invasion in gastric cancer cells. These results indicate that punicalagin promotes apoptosis and inhibits cell invasion in gastric cancer cells by activating caspase-3 and suppressing MMP-2, MMP-9, Snail, and Slug through the inhibition of the Erk and NF-κB pathways.
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BACKGROUND: Breast cancer is a heterogeneous disease categorized based on molecular characteristics, including hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression levels. The emergence of profiling technology has revealed multiple driver genomic alterations within each breast cancer subtype, serving as biomarkers to predict treatment outcomes. This study aimed to explore the genomic landscape of breast cancer in the Taiwanese population through comprehensive genomic profiling (CGP) and identify diagnostic and predictive biomarkers. METHODS: Targeted next-generation sequencing-based CGP was performed on 116 archived Taiwanese breast cancer specimens, assessing genomic alterations (GAs), including single nucleotide variants, copy number variants, fusion genes, tumor mutation burden (TMB), and microsatellite instability (MSI) status. Predictive variants for FDA-approved therapies were evaluated within each subtype. RESULTS: In the cohort, frequent mutations included PIK3CA (39.7%), TP53 (36.2%), KMT2C (9.5%), GATA3 (8.6%), and SF3B1 (6.9%). All subtypes had low TMB, with no MSI-H tumors. Among HR + HER2- patients, 42% (27/65) harbored activating PIK3CA mutations, implying potential sensitivity to PI3K inhibitors and resistance to endocrine therapies. HR + HER2- patients exhibited intrinsic hormonal resistance via FGFR1 gene gain/amplification (15%), exclusive of PI3K/AKT pathway alterations. Aberrations in the PI3K/AKT/mTOR and FGFR pathways were implicated in chemoresistance, with a 52.9% involvement in triple-negative breast cancer. In HER2+ tumors, 50% harbored GAs potentially conferring resistance to anti-HER2 therapies, including PIK3CA mutations (32%), MAP3K1 (2.9%), NF1 (2.9%), and copy number gain/amplification of FGFR1 (18%), FGFR3 (2.9%), EGFR (2.9%), and AKT2 (2.9%). CONCLUSION: This study presents CGP findings for treatment-naïve Taiwanese breast cancer, emphasizing its value in routine breast cancer management, disease classification, and treatment selection.
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Biomarcadores de Tumor , Neoplasias de la Mama , Mutación , Humanos , Femenino , Taiwán , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Adulto , Anciano , Secuenciación de Nucleótidos de Alto Rendimiento , Variaciones en el Número de Copia de ADN , Genómica/métodos , Fosfatidilinositol 3-Quinasa Clase I/genética , Inestabilidad de Microsatélites , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Perfilación de la Expresión GénicaRESUMEN
Despite neoadjuvant chemoradiotherapy (CRT) being the established standard for treating advanced rectal cancer, clinical outcomes remain suboptimal, necessitating the identification of predictive biomarkers for improved treatment decisions. Previous studies have hinted at the oncogenic properties of the Fc fragment of IgG binding protein (FCGBP) in various cancers; however, its clinical significance in rectal cancer remains unclear. In this study, we first conducted an analysis of a public transcriptome comprising 46 rectal cancer patients. Focusing on cell adhesion during data mining, we identified FCGBP as the most upregulated gene associated with CRT resistance. Subsequently, we assessed FCGBP immunointensity using immunohistochemical staining on 343 rectal cancer tissue blocks. Elevated FCGBP immunointensity correlated with lymph node involvement before treatment (p = 0.001), tumor invasion, and lymph node involvement after treatment (both p < 0.001), vascular invasion (p = 0.001), perineural invasion (p = 0.041), and reduced tumor regression (p < 0.001). Univariate analysis revealed a significant association between high FCGBP immunoexpression and inferior disease-specific survival, local recurrence-free survival, and metastasis-free survival (all p ≤ 0.0002). Furthermore, high FCGBP immunoexpression independently emerged as an unfavorable prognostic factor for all three survival outcomes in the multivariate analysis (all p ≤ 0.025). Enriched pathway analysis substantiated the role of FCGBP in conferring resistance to radiation. In summary, our findings suggest that elevated FCGBP immunoexpression in rectal cancer significantly correlates with a poor response to CRT and diminished patient survival. FCGBP holds promise as a valuable prognostic biomarker for rectal cancer patients undergoing CRT.
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Quimioradioterapia , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/metabolismo , Neoplasias del Recto/patología , Neoplasias del Recto/genética , Neoplasias del Recto/mortalidad , Femenino , Masculino , Persona de Mediana Edad , Quimioradioterapia/métodos , Anciano , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Pronóstico , Resultado del Tratamiento , Terapia Neoadyuvante/métodos , AdultoRESUMEN
BACKGROUND: Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patient-specific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. METHODS: A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. RESULTS: Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. CONCLUSION: In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decision-making more accurately for those patients.
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Biomarcadores de Tumor , Neoplasias del Recto , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Quimioradioterapia , Pronóstico , Estudios Prospectivos , Neoplasias del Recto/genética , Neoplasias del Recto/terapiaRESUMEN
Cholangiocarcinoma is the most common malignant bile duct tumor in Southeast Asia. The special location of cholangiocarcinoma leads to it being difficult to diagnose. Currently, the progress in clinical prognosis outcomes remains abysmal owing to the lack of definitive diagnostic criteria. Therefore, uncovering the potential markers for cholangiocarcinoma is a pressing issue. Ubiquitin-conjugating enzyme E2 C (UBE2C) is a critical ubiquitination enzyme; it is involved in the tumorigenesis of various malignancies and affects the patient's prognosis. However, there is currently no relevant literature to indicate whether UBE2C is related to the clinical survival outcome of cholangiocarcinoma patients. In this report, we mined the published cholangiocarcinoma transcriptome data set (GSE26566), compared it with the ubiquitination-associated gene (GO:0016567), and identified that UBE2C was highly expressed in cholangiocarcinoma tumor tissue. Moreover, high expression of UBE2C was markedly correlated with surgical margin, primary tumor, histological variants, and histological grade. More specifically, high expression of UBE2C was negatively associated with overall survival, disease-specific survival, local recurrence-free survival, and metastasis-free survival in patients with cholangiocarcinoma. Our findings demonstrate that UBE2C may provide a potential therapeutic marker and prognostic factor for cholangiocarcinoma patients.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Pronóstico , Enzimas Ubiquitina-Conjugadoras/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , Colangiocarcinoma/genética , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/genética , Conductos Biliares Intrahepáticos/metabolismoRESUMEN
Purpose: The purpose of this study was to explore the anticancer effect of punicalagin, an abundant bioactive tannin compound isolated from Punica granatum L., on three colon cancer cell lines, namely, HCT 116, HT-29, and LoVo.Research Design: Normal and colon cancer cells were treated with different concentrations of punicalagin for different periods. Data Collection and Analysis: Cell viability was measured with a CCK-8 assay. Programmed cell death and invasion were analyzed using an annexin V and cell death kit and a cell invasion analysis kit. The expression of active caspase-3, MMP-2, MMP-9, Snail, and Slug were measured by Western blot.Results: The results of the cell viability analysis showed that punicalagin was cytotoxic to colon cancer cells, but it was not to normal cells in a dose- and time-dependent manner. Additionally, punicalagin induced apoptosis in colon cancer cells (shown by the cumulative percentage of colorectal cancer cells in early and late apoptosis). It was found that caspase-3 activity increased following punicalagin treatment. Western blot results also showed that punicalagin increased the expression of activated caspase-3. In contrast, punicalagin inhibited the invasion of colon cancer cells. Further, treatment of colon cancer cells with punicalagin suppressed the expression of MMP-2, MMP-9, Snail, and Slug. Conclusions: These results showed that the activation of caspase-3 and the inhibition of MMP-2, MMP-9, Snail and Slug were involved in the effects of punicalagin on colon cancer cells.
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Antineoplásicos , Neoplasias del Colon , Humanos , Caspasa 3 , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz , Línea Celular Tumoral , Proliferación Celular , Antineoplásicos/farmacología , ApoptosisRESUMEN
Cholangiocarcinoma is a common malignancy with increasing incidence worldwide. Most patients are diagnosed at the advanced stage with poor survival rate. Laminin subunit γ2 (LAMC2) is a heparin binding-associated gene involved in tumorigenesis and has been implicated in the prognosis of various types of cancers. However, it is unclear whether expression of LAMC2 is associated with the clinical outcome of patients with cholangiocarcinoma. In the present study, the role and prognostic value of LAMC2 expression in patients with cholangiocarcinoma was investigated. Clinical information and pathological characteristics were analyzed and the association between LAMC2 expression and clinical characteristics, pathological findings and patient outcomes, including metastasis-free and disease-specific survival, were investigated. Data from 182 patients with cholangiocarcinoma were evaluated. High LAMC2 expression was associated with higher tumor stage (P<0.001), large duct type (P=0.024) and poor histological grade (P=0.002). Kaplan-Meier analysis showed high LAMC2 expression was associated with lower overall (P=0.003), disease-specific (P=0.0025), local recurrence-free (P<0.0001) and metastasis-free survival (P<0.0001). Moreover, multivariate analysis demonstrated that increased LAMC2 expression was a significant predictive risk factor for overall [hazard ratio (HR) 1.713; P=0.034], disease-specific (HR 2.011; P=0.039), local recurrence-free (HR 2.721; P<0.001) and metastasis-free survival (HR 3.117; P<0.001). Gene enrichment analysis using Gene Ontology showed that terms associated with LAMC2 upregulation were 'regulation of platelet-derived growth factor receptor-ßsignaling pathway' and 'platelet-derived growth factor receptor-ß signaling pathway'. The present study indicated that LAMC2 was upregulated in cholangiocarcinoma tumor tissue and had an inverse association with overall, disease-specific, local recurrence-free and metastasis-free survival in patients with cholangiocarcinoma. These results suggested that LAMC2 may serve as a potential biomarker for cholangiocarcinoma.
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Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p < 0.001), large duct type (p = 0.004), and poorly differentiated histology (p = 0.002). COMP overexpression correlates with poorer DFS (HR, 3.651; p = 0.001), OS (HR, 1.827; p = 0.023), LRFS (HR, 4.077; p < 0.001), and MFS (HR, 3.718; p < 0.001). High COMP expression ties to worse overall survival (p = 0.0001), DSS (p < 0.0001), LRFS (p < 0.0001), and MFS (p < 0.0001). In conclusion, COMP overexpression links to poor prognosis and pathological features in iCCA, indicating its potential as a biomarker.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Proteína de la Matriz Oligomérica del Cartílago/genética , Proteína de la Matriz Oligomérica del Cartílago/metabolismo , Colangiocarcinoma/patología , Pronóstico , Estudios RetrospectivosRESUMEN
Intrahepatic cholangiocarcinoma (IHCC) is the second most common malignant neoplasm of the liver. In spite of the increasing incidence worldwide, it is relatively rare in Western countries. IHCC is relatively common in Eastern and Southeastern Asia. Patients with IHCC are usually diagnosed at an advanced stage, therefore, the clinical outcome is dismal. Dysregulation of urea cycle metabolic enzyme expression is found in different types of cancers. Nevertheless, a comprehensive evaluation of genes related to the urea cycle (i.e., GO:0000050) has not been conducted in IHCC. By performing a comparative analysis of gene expression profiles, we specifically examined genes associated with the urea cycle (GO:0000050) in a publicly accessible transcriptomic dataset (GSE26566). Interestingly, CPS1 was identified as the second most prominently down-regulated gene in this context. Tumor tissues of 182 IHCC patients who underwent curative-intent hepatectomy were enrolled. The expression level of CPS1 protein in our IHCC cohort was assessed by immunohistochemical study. Subsequent to that, statistical analyses were carried out to examine the expression of CPS1 in relation to various clinicopathological factors, as well as to assess its impact on survival outcomes. We noticed that lower immunoreactivity of CPS1 in IHCC was associated with tumor progression (pT status) with statistical significance (p = 0.003). CPS1 underexpression was not only negatively correlated to overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and metastasis-free survival (MeFS) in univariate analysis but also an independent prognosticator to forecast poorer clinical outcome for all prognostic indices (OS, DFS, LRFS and MeFs) in patients with IHCC (all p ≤ 0.001). These results support that CPS1 may play a crucial role in IHCC oncogenesis and tumor progression and serve as a novel prognostic factor and a potential diagnostic and theranostic biomarker.
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Portal vein cannulation is a very rare complication of endoscopic retrograde cholangiopancreatography (ERCP). In most reported cases, the event was managed safely with immediate catheter, guidewire withdrawn and procedure termination. Here, we report an unusual case of portobiliary fistula created during ERCP. To our knowledge, this is the first report of such case managed with immediate surgical biliary exposure.
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BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor with an increasing incidence worldwide. Although radiation therapy has improved the therapeutic efficiency of CCA treatment, differential expression of genes among cholangiocarcinoma subtypes has been revealed through precise sequencing. However, no specific molecular therapeutic targets or biomarkers have been figured out for use in precision medicine, and the exact mechanism by which antitumorigenic effects occur is still unclear. Therefore, it is necessary to conduct further studies on the development and mechanisms associated with CCA. METHODS: We examined the clinical data and pathological features of patients with cholangiocarcinomas. We investigated the associations between DNA Topoisomerase II Alpha (TOP2A) expression and patient outcomes, such as metastasis-free survival (MFS) and disease-specific survival (DSS), as well as clinical characteristics and pathological results. RESULTS: TOP2A expression was shown to be upregulated in CCA tissue sections by immunohistochemistry staining and data mining. Moreover, we observed that the TOP2A expression correlated with clinical features, such as the primary tumor stage, histological variants, and patients with hepatitis. Furthermore, high expression of TOP2A was associated with worse survival outcomes in terms of the overall survival (p < 0.0001), disease-specific survival (p < 0.0001), and metastasis-free survival (p < 0.0001) compared with patients in the low TOP2A expression group. This indicates that a high level of TOP2A expression is related to an unfavorable prognosis. CONCLUSIONS: Our results show that TOP2A is highly expressed in CCA tissues, and its upregulation is correlated with the primary disease stage and poor prognosis significantly. Consequently, TOP2A is a prognostic biomarker and a novel therapeutic target for the treatment of CCA.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Pronóstico , ADN-Topoisomerasas de Tipo II/genética , ADN-Topoisomerasas de Tipo II/metabolismo , Colangiocarcinoma/genética , Neoplasias de los Conductos Biliares/genética , Conductos Biliares Intrahepáticos/metabolismo , Biomarcadores de Tumor/genéticaRESUMEN
Colorectal cancer (CRC) is one of the types of cancers with a high incidence and is ranked the 3rd among men and 2nd among women worldwide. The purpose of this study was to investigate the correlation between non-SMC condensin I complex subunit G (NCAPG) and the prognosis of CRC and its function in CRC cells. The expression of NCAPG in colorectal tissues and cells was detected by immunoblotting and immunohistochemistry. Kaplan-Meier analysis was used to analyze the correlation between NCAPG and CRC prognosis. RNAi technology was used to investigate how NCAPG inhibition affected the proliferation and migration of CRC cells. Overexpression of NCAPG was positively correlated with several clinicopathologic characteristics, including T stage (P = 0.0198), M stage (P = 0.0005), and TNM stage (P < 0.0001). Kaplan-Meier analysis showed that the overexpression of NCAPG was also negatively correlated with disease-free survival and overall survival. In the culture of CRC cells, the knockdown of NCAPG inhibited the proliferation, migration, and invasion of the cells. Meanwhile, it was also found that NCAPG knockdown could interfere with G2/M-G1 transition in the cell cycle, resulting in the inhibition of cell proliferation. The overexpression of NCAPG may serve as a candidate biomarker for CRC prognosis. NCAPG is also a potential therapeutic target for CRC.
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Carcinogénesis , Neoplasias Colorrectales , Masculino , Humanos , Femenino , Línea Celular Tumoral , Pronóstico , Interferencia de ARN , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Regulación Neoplásica de la Expresión Génica , Proteínas de Ciclo Celular/metabolismoRESUMEN
The C-C chemokine motif ligand 5 (CCL5) and its receptors have recently been thought to be substantially involved in the development of obesity-associated adipose tissue inflammation and insulin resistance. However, the respective contributions of tissue-derived and myeloid-derived CCL5 to the etiology of obesity-induced adipose tissue inflammation and insulin resistance, and the involvement of monocytic myeloid-derived suppressor cells (MDSCs), remain unclear. This study used CCL5-knockout mice combined with bone marrow transplantation (BMT) and mice with local injections of shCCL5/shCCR5 or CCL5/CCR5 lentivirus into bilateral epididymal white adipose tissue (eWAT). CCL5 gene deletion significantly ameliorated HFD-induced inflammatory reactions in eWAT and protected against the development of obesity and insulin resistance. In addition, tissue (non-hematopoietic) deletion of CCL5 using the BMT method not only ameliorated adipose tissue inflammation by suppressing pro-inflammatory M-MDSC (CD11b+Ly6G-Ly6Chi) accumulation and skewing local M1 macrophage polarization, but also recruited reparative M-MDSCs (CD11b+Ly6G-Ly6Clow) and M2 macrophages to the eWAT of HFD-induced obese mice, as shown by flow cytometry. Furthermore, modulation of tissue-derived CCL5/CCR5 expression by local injection of shCCL5/shCCR5 or CCL5/CCR5 lentivirus substantially impacted the distribution of pro-inflammatory and reparative M-MDSCs as well as macrophage polarization in bilateral eWAT. These findings suggest that an obesity-induced increase in adipose tissue CCL5-mediated signaling is crucial in the recruitment of tissue M-MDSCs and their trans-differentiation to tissue pro-inflammatory macrophages, resulting in adipose tissue inflammation and insulin resistance.
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Tejido Adiposo , Quimiocina CCL5 , Inflamación , Células Supresoras de Origen Mieloide , Receptores CCR5 , Animales , Ratones , Tejido Adiposo/química , Tejido Adiposo/metabolismo , Dieta Alta en Grasa/efectos adversos , Inflamación/metabolismo , Resistencia a la Insulina/genética , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Obesos , Células Supresoras de Origen Mieloide/metabolismo , Obesidad/metabolismo , Receptores CCR5/genética , Receptores CCR5/metabolismo , Quimiocina CCL5/metabolismo , Quimiocina CCL5/farmacologíaRESUMEN
Objective: To reduce the risk of locoregional recurrence, the addition of neoadjuvant concurrent chemoradiotherapy (CCRT) is recommended before surgical management for rectal cancer patients. However, despite identical tumor histology, individual patient response to neoadjuvant CCRT varies greatly. Accordingly, a comprehensive molecular characterization that is used to predict CCRT efficacy is instantly needed. Methods: Pearson's chi-squared test was utilized to correlate dehydrogenase/reductase 9 (DHRS9) expression with clinicopathological features. Survival curves were created applying the Kaplan-Meier method, and the log-rank test was conducted to compare prognostic utility between high and low DHRS9 expression groups. Multivariate Cox proportional hazards regression analysis was applied to identify independent prognostic biomarkers based on variables with prognostic utility at the univariate level. Results: Utilizing a public transcriptome dataset, we identified that the DHRS9 gene is the most considerably upregulated gene related to epithelial cell differentiation (GO: 0030855) among rectal cancer patients with CCRT resistance. Employing immunohistochemical staining, we also demonstrated that high DHRS9 immunoexpression is considerably associated with an aggressive clinical course and CCRT resistance in our rectal cancer cohort. Among all variables with prognostic utility at the univariate level, only high DHRS9 immunoexpression was independently unfavorably prognostic of all three endpoints (all p ≤ 0.048) in the multivariate analysis. In addition, applying bioinformatic analysis, we also linked DHRS9 with unrevealed functions, such as keratan sulfate and mucin synthesis which may be implicated in CCRT resistance. Conclusion: Altogether, DHRS9 expression may serve as a helpful predictive and prognostic biomarker and assist decision-making for rectal cancer patients who underwent neoadjuvant CCRT.
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Sulfato de Queratano , Neoplasias del Recto , Humanos , Sulfato de Queratano/uso terapéutico , Inmunohistoquímica , Supervivencia sin Enfermedad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias del Recto/terapia , Quimioradioterapia , Terapia Neoadyuvante , Pronóstico , Mucinas/uso terapéutico , Oxidorreductasas/uso terapéutico , Estudios RetrospectivosRESUMEN
Purpose: For locally advanced rectal cancer, neoadjuvant concurrent chemoradiotherapy (CCRT) allows tumor downstaging and makes curative radical proctectomy possible. However, we lack a genetic biomarker to predict cancer prognosis or treatment response. We investigated the association between ubiquitin D (UBD) expression and clinical outcomes in rectal cancer patients receiving CCRT. Patients and Methods: We analyzed the genes associated with the protein modification process (GO:0036211) and identified the UBD gene as the most relevant among the top 7 differentially expressed genes associated with CCRT resistance. We collected tissue specimens from 172 rectal cancer patients who had received CCRT followed by a curative proctectomy. We examine the relationship between UBD expression and patient characteristics, pathological findings, and patient survival, such as metastasis-free survival (MeFS) and disease-specific survival. Results: Upregulated UBD expression was associated with lower pre-CCRT tumor T stage (P = 0.009), lower post-CCRT tumor T stage (P < 0.001), lower post-CCRT nodal stage (P < 0.001), less vascular invasion (P = 0.015), and better tumor regression (P < 0.001). Using univariate analysis, we found that high UBD expression was correlated with better disease-free survival (DFS) (P < 0.0001), local recurrence-free survival (LRFS) (P < 0.0001) and MeFS (P < 0.0001). Moreover, multivariate analysis demonstrated that high UBD expression was associated with superior DFS (P < 0.001), LRFS (P = 0.01), and MeFS (P = 0.004). Conclusion: UBD upregulation was linked to better clinical prognosis, favorable pathological features, and good treatment response in rectal cancer patients undergoing CCRT. These results suggest UBD is a biomarker for rectal cancer.
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For rectal cancer patients with stage T3-4 disease or positive lymph node, neoadjuvant concurrent chemoradiotherapy (CCRT) has become the standard treatment, but the clinical outcomes are still far from satisfactory. Accordingly, a more precise predictive tool such as genetic biomarkers is urgently required to optimize therapy decisions. Colorectal cancer (CRC) development has been considerably correlated with cellular metabolic process involving nucleotides, but the underlying molecular mechanisms remain unclear. In this study, we employed a transcriptome dataset comprising 46 rectal adenocarcinoma patients undergoing preoperative CCRT and focused on nucleobase-containing compound metabolic process (GO: 0055134) for data mining. We identified solute carrier family 28 member 2 (SLC28A2) as the most considerably upregulated gene among rectal cancer patients with CCRT resistance. Afterwards, there were a total of 172 rectal cancer tissue blocks procuring from our biobank, and the immunointensity of SLC28A2 was appraised utilizing immunohistochemical staining. Strong SLC28A2 immunointensity was significantly linked to female patients (p = 0.032), vascular invasion (p = 0.021), and post-CCRT tumor invasion and regional lymph node involvement (p < 0.001 and p = 0.005). Notably, patients with strong SLC28A2 immunointensity had no tumor downstaging (p < 0.001). Univariate analysis revealed that high SLC28A2 immunoexpression was considerably unfavorably linked to all three endpoints: local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS) (all p ≤ 0.0333). Moreover, both high SLC28A2 immunoexpression and low tumor regression grade were independently unfavorable prognostic factors for all three endpoints (all p ≤ 0.013) in the multivariate analysis. Utilizing function prediction analysis, SLC28A2 upregulation was more likely to be linked with stem cell homeostasis in rectal cancer. In brief, we demonstrated that high SLC28A2 immunoexpression is substantially linked to an advanced stage, poor response to CCRT, and worse patient survival. Consequently, SLC28A2 expression can be a valuable predictive and prognostic marker for rectal cancer patients and be an encouraging therapeutic target for those with CCRT resistance.
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Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Femenino , Pronóstico , Biomarcadores de Tumor/análisis , Neoplasias del Recto/patología , Quimioradioterapia , Supervivencia sin EnfermedadRESUMEN
Background: Colorectal cancer is one of the leading cancers worldwide. This study aimed to investigate the mortality differences between 2 primary tumor locations, the proximal/distal colon and rectosigmoid junction (RSJ)/rectum, after adjusting for comorbidities. Methods: The Taiwan Cancer Registry linked with Taiwan's National Health Insurance Research Database was used to estimate the 5-year mortality rate among patients with colorectal cancer. A total of 73 769 individuals were enrolled in the study, which included 44 234 patients with proximal and distal colon cancers and 29 535 patients with RSJ and rectal cancers. Potential mortality risk was calculated using Cox regression analysis. Results: The mortality rates due to the location of the cancer in the proximal/distal colon and RSJ/rectum were 45.27% and 42.20%, respectively. After adjustment for age, sex, comorbidities, and clinical stages, the proximal/distal colon had a 1.03-fold higher 5-year overall mortality rate than RSJ/rectal cancer (95% confidence interval = 1.00-1.05). Proximal and distal colon cancers had a worse prognosis and survival than RSJ and rectal colon cancers in women and older patients (⩾70 years). Comorbidities had different effects on mortality in the proximal/distal colon and RSJ/rectum. Conclusions: Tumor location is associated with the prognosis of patients with colorectal cancer. It is important to treat patients beyond their cancer treatment, and to manage their comorbidities.
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Most new cases and the highest mortality rates of breast cancer occur among middle-aged and old women. The recurrence rate of early-stage invasive ductal carcinoma (IDC) among women aged ≥ 50 years and receiving different treatments remains unclear. Therefore, this study was conducted to determine these rates. We used Surveillance, Epidemiology, and End Results (SEER) data for this nationwide population-based cohort study. All women aged ≥ 50 years and diagnosed with early-stage IDC between 2000 and 2015 were identified and divided into three treatment groups, namely, breast conservation therapy (BCT), mastectomy alone (MAS), and mastectomy with radiation therapy (MAS + RT). The recurrence rates of IDC among these groups were then compared. The BCT group had a lower short-term recurrence risk than the MAS and MAS + RT groups (hazard ratio [HR]: 1.00 vs. 2.90 [95% CI 1.36-2.66] vs. 2.07 [95% CI 0.97-4.44]); however, the BCT group also had a higher long-term recurrence risk than MAS and MAS + RT groups (HR 1.00 vs. 0.30 [95% CI 0.26-0.35] vs. 0.43 [95% CI 0.30-0.63]). The high long-term recurrence rate of the BCT group was especially prominent at the 10- and 15-year follow-ups. The results provide valuable evidence of the most reliable treatment strategy for this population. Further studies including more variables and validation in other countries are warranted to confirm our findings.
Asunto(s)
Neoplasias de la Mama , Carcinoma Ductal de Mama , Carcinoma Ductal , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Carcinoma Ductal/patología , Carcinoma Ductal de Mama/epidemiología , Carcinoma Ductal de Mama/terapia , Estudios de Cohortes , Femenino , Humanos , Masculino , Mastectomía/métodos , Mastectomía Segmentaria , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de NeoplasiasRESUMEN
Background: Globally, gastric cancer is ranked 4th and 3rd in terms of incidence and mortality rate among all cancer types. This study aimed to examine the relationship between G protein-coupled receptor kinase 3 (GRK3) and gastric cancer prognosis and investigate the role of GRK3 in gastric cancer carcinogenesis. Methods: GRK3 level in gastric tissues and cells were determined using immunohistochemistry and immunoblotting. Kaplan-Meier analysis with the log-rank test was employed to evaluate the relationship between GRK3 expression and gastric cancer prognosis. RNAi technology was applied to examine the effects of GRK3 inhibition on gastric cancer proliferation and spread. Results: GRK3 overexpression was correlated significantly with lymphatic metastasis (P = 0.0011), distant metastasis (P < 0.0001), TNM stage (P = 0.0035), and vascular invasion (P = 0.0025). Kaplan-Meier survival analysis showed that the disease-free survival and overall survival of patients with high GRK3 expression were significantly shorter than those of patients with low GRK3 expression. Multivariate Cox regression analysis also showed that the overexpression of GRK3 was an independent prognostic biomarker of gastric cancer (P = 0.029). In cultured gastric cancer cells, GRK3 knockdown inhibited cell proliferation, migration, and invasion. Further analysis revealed that more GRK3-knockdown cells were in G0/G1 phase and few cells were in S phase, thereby inhibiting cell proliferation. Conclusions: GRK3 overexpression can be a candidate biomarker for gastric cancer prognosis. GRK3 is also a potential therapeutic target for gastric cancer.