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Background: The hemoglobin-albumin-lymphocyte-platelet (HALP) score functions as a comprehensive index that assesses the systemic inflammatory response, nutritional, and immune status. This study aimed to explore the relationship between preoperative HALP score and the prognosis of BC patients and to develop predictive nomograms. Methods: Clinicopathological data were collected for BC patients who underwent mastectomy between December 2010 and April 2014 from Sun Yat-sen University Cancer Center. The optimal cutoff value for HALP was determined by maximally selected rank statistics for overall survival data. Propensity score matching (PSM) was applied to develop comparable cohorts of high-HALP group and low-HALP group. Kaplan–Meier curves and Cox regression analyses were performed to determine the impact of HALP on BC patients. Prognostic nomograms were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), calibration plots, and decision curves analysis (DCA) were applied to evaluate the prognostic performance of the nomograms. Results: A total of 1,856 patients were included as the primary cohort, and 1,470 patients were matched and considered as the PSM cohort. In the primary cohort, the 5-year overall survival (OS) and progression-free survival (PFS) rates for high-HALP group (≥ 47.89) and low-HALP group (< 47.89) were 94.4% vs. 91.0% (P = 0.005) and 87.8% vs. 82.1% (P = 0.005), respectively. Similar results were observed in PSM cohort (5-year OS, 94.3% vs. 90.8%, P = 0.015; 5-year PFS, 87.5% vs. 83.2%, P = 0.036). Notably, multivariate Cox regression analysis in the PSM cohort showed that HALP could independently predict BC patient prognosis in both OS (HR: 0.596, 95%CI [0.405–0.875], P = 0.008) and PFS (HR: 0.707, 95%CI [0.538–0.930], P = 0.013). OS and PFS nomograms showed excellent predictive performance with the C-indexes of 0.783 and 0.720, respectively. The calibration plots and DCA also indicated the good predictability of the nomograms. Finally, subgroup analysis further demonstrated a favorable impact of HALP on both OS and PFS. Conclusion: Preoperative HALP score can be used as a reliable independent predictor of OS and PFS in BC patients, and the nomograms may provide a personalized treatment strategy. [ABSTRACT FROM AUTHOR]

Background: The C-reactive protein-albumin-lymphocyte (CALLY) score is a novel indicator associated with inflammation, immunity, and nutrition, utilized for cancer prognostic stratification. This study aimed to evaluate the integrated prognostic significance of the pre-treatment CALLY score and Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) patients and to develop prognostic models. Patients and Methods: A total of 1707 NPC patients from September 2015 to December 2017 were retrospectively enrolled. The cut-off point for the CALLY score, determined by maximum selected rank statistics, integrates with the published cut-off point for pre-EBV DNA to develop a comprehensive index. Subsequently, patients were randomly allocated in a 1:1 ratio into training and validation cohorts. Survival analysis was conducted using the Kaplan-Meier method with Log rank tests, and the Cox proportional hazards model was applied to identify independent prognostic factors for constructing predictive nomograms. The predictive ability of the nomograms were assessed through the concordance index (C-index), calibration curves, and decision curve analysis. Results: By integrating CALLY scores and EBV-DNA levels, patients were categorized into three risk clusters. Kaplan-Meier curves reveal significant differences in overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) outcomes among different risk groups (all P values < 0.05). Multivariate analysis revealed that CALLY-EBV DNA index serves as an independent prognostic factor for the OS, DMFS, and LRRFS. The prognostic nomograms based on the CALLY-EBV DNA index provided accurate predictions for 1-year, 3-year, and 5-year OS, DMFS, and LRRFS. Additionally, compared to the traditional TNM staging system, the nomograms exhibited enhanced discriminatory power, calibration capability, and clinical applicability. All results were in agreement with the validation cohort. Conclusion: The CALLY-EBV DNA index is an independent prognostic biomarker. The nomogram prediction models, constructed based on the CALLY-EBV DNA index, demonstrates superior predictive performance compared to the traditional TNM staging. [ABSTRACT FROM AUTHOR]

Background: The nutritional risk index (NRI) is an independent prognostic factor for overall survival in various cancers, but its prognostic value in breast cancer remains unclear. This study aimed to explore the relationship between the NRI and overall survival (OS) in breast cancer and to develop a predictive nomogram. Methods: We retrospectively enrolled 1347 breast cancer patients who underwent mastectomy or lumpectomy between January 2011 and November 2012. Using a cutoff value of 110.59, patients were divided into a high-NRI group and a low-NRI group. OS was compared between the two groups. Clinicopathological factors independently associated with survival were used to construct a predictive nomogram. Results: Of the 1347 patients, 534 patients were classified as high NRI and 813 as low NRI. OS was significantly shorter in low-NRI patients. The 3- and 5-year OS rates were 87.3% and 73.4%, respectively, in the high-NRI group whereas they were 83.0% and 67.2%, respectively, in the low-NRI group. Cox regression analysis found that histopathological type, tumor size, lymph node status, progesterone receptor (PR) status, Ki-67, and NRI were independently associated with OS. Conclusions: NRI is an independent prognostic factor of OS in breast cancer patients. The proposed nomogram model may be a useful tool for individualized survival prediction. [ABSTRACT FROM AUTHOR]

Purpose: We attempted to explore the prognostic value of baseline inflammatory and nutritional biomarkers at diagnosis in patients with early-stage breast cancer and develop a novel scoring system, the inflammatory-nutritional prognostic score (INPS). Patients and Methods: We collected clinicopathological and baseline laboratory data of 1259 patients with early-stage breast cancer between December 2010 and November 2012 from Sun Yat-sen University Cancer Center. Eligible patients were randomly divided into training and validation cohorts (n = 883 and 376, respectively) in a 7:3 ratio. We selected the most valuable biomarkers to develop INPS by the least absolute shrinkage and selection operator (LASSO) Cox regression model. A prognostic nomogram incorporating INPS and other independent clinicopathological factors was developed based on the stepwise multivariate Cox regression method. Then, we used the concordance index (C-index), calibration plot, and time-dependent receiver operating characteristic (ROC) analysis to evaluate the prognostic performance and predictive accuracy of the predictive nomogram. Results: Four inflammatory-nutritional biomarkers, including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), prognostic nutritional index (PNI), and albumin-alkaline phosphatase ratio (AAPR), were selected using the LASSO Cox analysis to construct INPS, which remained an independent prognostic indicator per the multivariate Cox regression analysis. Patients were stratified into low- and high-INPS groups based on the cutoff INPS determined by the maximally selected rank statistics. The prognostic model for overall survival consisting of INPS and other independent clinicopathological indicators showed excellent discrimination with C-indexes of 0.825 (95% confidence interval [CI]: 0.786– 0.864) and 0.740 (95% CI: 0.657– 0.822) in the training and validation cohorts, respectively. The time-dependent ROC curves showed a higher predictive accuracy of our prognostic nomogram than that of traditional tumor-node-metastasis staging. Conclusion: Baseline INPS is an independent indicator of OS in patients with early-stage breast cancer. The INPS-based prognostic nomogram could be used as a practical tool for individualized prognostic predictions. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is a conventional and effective local treatment for breast cancer. However, residual or recurrent tumors appears frequently because of radioresistance. Novel predictive marker and the potential therapeutic targets of breast cancer radioresistance needs to be investigated. Methods: In this study, we screened all 10 asparagine-linked glycosylation (ALG) members in breast cancer patients' samples by RT-PCR. Cell viability after irradiation (IR) was determined by CCK-8 assay and flow cytometry. The radiosensitivity of cell lines with different ALG3 expression was determined with the colony formation assay by fitting the multi-target single hit model to the surviving fractions. Cancer stem-like traits were assessed by RT-PCR, Western blot, and flow cytometry. The mechanisms of ALG3 influencing radiosensitivity was detected by Western blot and immunoprecipitation. And the effect of ALG3 on tumor growth after IR was verified in an orthotopic xenograft tumor models. The association of ALG3 with prognosis of breast cancer patients was confirmed by immunohistochemistry. Results: ALG3 was the most significantly overexpressing gene among ALG family in radioresistant breast cancer tissue. Overexpression of ALG3 predicted poor clinicopathological characteristics and overall survival (OS), and early local recurrence-free survival (LRFS) in breast cancer patients. Upregulating ALG3 enhanced radioresistance and cancer stemness in vitro and in vivo. Conversely, silencing ALG3 increased the radiosensitivity and repressed cancer stemness in vitro, and more importantly inhibition of ALG3 effectively increased the radiosensitivity of breast cancer cells in vivo. Mechanistically, our results further revealed ALG3 promoted radioresistance and cancer stemness by inducing glycosylation of TGF-β receptor II (TGFBR2). Importantly, both attenuation of glycosylation using tunicamycin and inhibition of TGFBR2 using LY2109761 differentially abrogated the stimulatory effect of ALG3 overexpression on cancer stemness and radioresistance. Finally, our findings showed that radiation played an important role in preventing early recurrence in breast cancer patients with low ALG3 levels, but it had limited efficacy in ALG3-overexpressing breast cancer patients. Conclusion: Our results suggest that ALG3 may serve as a potential radiosensitive marker, and an effective target to decrease radioresistance by regulating glycosylation of TGFBR2 in breast cancer. For patients with low ALG3 levels, radiation remains an effective mainstay therapy to prevent early recurrence in breast cancer. [ABSTRACT FROM AUTHOR]

Correction to: ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF- receptor II in breast cancer 5 ALG3 enhances radioresistance via regulation of TGFBR2 glycosylation. a Downshift of TGFBR2 bands in ALG3-sg cells was detected by Western blot. The round spots are mannose, the square ones are acetylglucosamine, and the red spot is the initial of the N-glycosylation site, which is initiated by ALG3. d TGFBR2 band shift could be seen in ALG3-sg cells or cells treated by tunicamycin. [Extracted from the article]

Background: Prostate tumor overexpressed 1 (PTOV1) has been reported to contribute to increased cancer proliferation. However, the clinical significance of PTOV1 in the development and progression of nasopharyngeal carcinoma (NPC) is unclear. Our study aimed to investigate the expression pattern of PTOV1 in NPC and its correlation with clinicopathological features of patients. Methods: Western blotting and real-time PCR were conducted to examine PTOV1 expression levels in NPC cell lines and biopsy tissues compared with normal controls. Immunohistochemistry (IHC) was performed to analyze PTOV1 protein expression in paraffin-embedded tissues from 123 patients. Statistical analyses were applied to evaluate the clinical significance of PTOV1 expression. Results: PTOV1 mRNA and protein levels were upregulated in NPC cell lines and clinical samples. IHC analyses showed that PTOV1 was highly expressed in 68 (55.3%) of 123 NPC specimens. Statistical analysis revealed that PTOV1 expression was significantly correlated with clinical stage (P < 0.001), T classification (P = 0.042) and N classification (P = 0.001). Patients with a higher PTOV1 expression had shorter overall survival compared with those with a lower PTOV1 expression level, especially in lower N stage patients. Multivariate analyses suggested that PTOV1 expression was an independent prognostic marker for survival in NPC patients. Conclusions: Our data demonstrated that PTOV1 overexpression is associated with poor survival outcomes of NPC patients, especially in N0-1 patients. Hence, PTOV1 may help to detect early lymph node metastasis of NPC patients and serve as an independent prognostic biomarker for human NPC. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the security of breast-conserving treatment (BCT) in young patients and the effect of regional radiation therapy on young patients with 1-3 positive nodes (N+) treated with BCT. Methods: In this prospective concurrent controlled study, 164 patients were defined as the BCT group, and regional radiation therapy was delivered to patients with 1-3 N+. Modified radical mastectomies (MRMs) were performed on 224 patients without regional radiation therapy. Results: The 9-year local recurrence (LR) rate of the BCT was 7 %, compared with 3 % in the MRM group ( p = 0.055). The 9-year regional recurrence (RR) rate was 6 % for the BCT group and 12 % for the MRM group ( p = 0.048). The distant metastasis (DM)-free and breast cancer-specific survival rates were similar between the two groups. RR was an independent prognostic factor for DM [hazard ratio 3.27; 95 % confidence interval (CI) 1.726-6.208] and breast cancer-specific survival (hazard ratio 5.814; 95 % CI 2.690-12.568), whereas LR was not an independent prognostic factor for DM or breast cancer-specific survival. Conclusions: Young patients treated with BCT have a higher LR rate than that of MRM. However, LR has no detrimental effect on DM-free and breast cancer-specific survival rates, whereas RR is a strong risk factor of DM and death. Regional radiation therapy for young patients with 1-3 N+ may reduce RR and improve survival rates. [ABSTRACT FROM AUTHOR]

Background: We previously found that r-hu-IFNgamma exerts a potent anti-tumor effect on human nasopharyngeal carcinoma xenografts in vivo. Considering the fact that the clinical use of recombinant IFNgamma is limited by its short half-life and systemic side effects, we developed a recombinant adenovirus, Ad-IFNgamma.Methods: Dynamic distribution of the adenovirus vector and expression of IFNgamma were evaluated by Q-PCR and ELISA after intratumoral administration of Ad-IFNgamma into CNE-2 xenografts.Results: Ad-IFNgamma DNA was mainly enriched in tumors where the Ad-IFNgamma DNA was injected (P < 0.05, compared to blood or parenchymal organs), as well as in livers (P < 0.05). Concentrations of Ad-IFNgamma DNA in other organs and blood were very low. Intratumoral Ad-IFNgamma DNA decreased sharply at high concentrations (9 x 10(5) copies/microg tissue DNA), and slowly at lower concentrations (1.7-2.9 x 10(5) copies/microg tissue DNA). IFNgamma was detected in the tumors and parenchymal organs. The concentration of IFNgamma was highest in the tumor (P < 0.05), followed by the liver and kidney (P < 0.05). High-level intratumoral expression of IFNgamma was maintained for at least 7 days, rapidly peaking on day 3 after injection of Ad-IFNgamma DNA.Conclusion: An IFNgamma gene delivered by an adenoviral vector achieved high and consistent intratumoral expression. Disseminated Ad-IFNgamma DNA and the transgene product were mainly enriched in the liver. [ABSTRACT FROM AUTHOR]