Anlotinib in patients with recurrent platinum resistant/refractory ovarian cancer: a prospective, single arm, phase II study.

OBJECTIVE: This study aimed to prospectively evaluate the efficacy and safety of anlotinib in patients with platinum resistant/refractory ovarian cancer. METHODS: In this prospective, single arm, phase II study, patients with platinum resistant/refractory ovarian cancer received anlotinib (12 mg once daily; days 1-14; 21 days per cycle) until disease progression, unacceptable toxicity, or study withdrawal. The study was conducted between May 2019 and May 2021. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression free survival, overall survival, and safety. An exploratory biomarker analysis was performed to evaluate the correlation of baseline TP53 mutation status with outcomes. RESULTS: 33 of 34 enrolled patients received at least one dose of anlotinib. The objective response rate was 31.2% (95% confidence interval (CI) 16.1% to 50.0%), with 2 (6.3%) complete and 8 (25.0%) partial responses. In total, 14 (43.8%) patients achieved stable disease, resulting in a disease control rate of 75.0% (95% CI 56.6% to 88.5%). With a median follow-up of 4.6 months (range 0.5-17.2) at data cut-off (September 16, 2022), median progression free survival was 5.3 months (95% CI 4.04 to 6.56) and median overall survival was not reached. In a subgroup analysis, patients with a TP53 mutation showed a trend towards worse progression free survival than those with the wild-type TP53 (4.4 months vs 8.4 months; hazard ratio 2.48 (95% CI 0.91 to 6.76), p=0.067). Common adverse events were hypertension (42.4%), hand-foot syndrome (27.3%), and fatigue (24.2%). Grade 3 events were reported in 3 (9.1%) patients and no grade 4-5 events or deaths were observed. CONCLUSION: Anlotinib showed antitumor activity with an acceptable safety profile in patients with platinum resistant/refractory ovarian cancer, and it might be a potential treatment in this population.

S100A11 promotes cell proliferation via P38/MAPK signaling pathway in intrahepatic cholangiocarcinoma.

S100A11 is reported to associate with progression and poor prognosis in several tumors. We previously reported that S100A11 was highly expressed in intrahepatic cholangiocarcinoma (ICC) cells and promoted TGF-ß1-induced EMT through SMAD2/3 signaling pathway. Here, we explored the prognostic role of S100A11 on ICC patients and preliminary molecular mechanisms how S100A11 regulated ICC cell proliferation. Our results showed that S100A11 was obviously increased in ICC tumor tissues. High expression of S100A11 was closely correlated with lymph node metastasis (LNM) and TNM stage and was an independent risk factor for patients' overall survival (OS) and recurrence-free survival (RFS). The nomograms comprising LNM and S100A11 achieved better predictive accuracy compared with TNM staging system for OS and RFS prediction. Silencing S100A11 significantly suppressed RBE cells and HCCC9810 cells proliferation, colony formation, and activation of P38/mitogen-activated protein kinase (MAPK) signaling pathway in vitro and inhibited tumor growth in vivo. In contrast, the overexpression of S100A11 in RBE cells and HCCC9810 cells achieved the opposite results. S100A11-induced proliferation was abolished after treatment with P38 inhibitor. Our findings suggest S100A11/P38/MAPK signaling pathway may be a potential therapeutic target for ICC patients.

Overexpression of interleukin-35 in intrahepatic cholangiocarcinoma is a prognostic indicator after curative resection.

Interleukin-35 (IL-35) is implicated in tumorigenesis, but its exact impact on intrahepatic cholangiocarcinoma (ICC) is not clear. The aim of the present study was to explore the specific effect of IL-35 on patient prognosis. Additionally, we formulated an effective prognostic nomogram for ICC patients after curative resection. Immunohistochemistry was applied to explore IL-35 expression as well as IL-35 receptor (IL-35R) in 102 ICC patients. Results showed that IL-35 was highly expressed in ICC tumor tissues and was positively associated with lymph node metastasis (LNM), TNM stage and vascular invasion and was an independent prognostic factor for patients' overall survival (OS) and recurrence-free survival (RFS). High expression of IL-35R (gp130 and IL-12Rß2) was also observed in ICC cancer tissues, but only gp130 was an independent prognostic factor for OS and RFS and was indispensable in IL-35-mediated ICC clinical prognosis. The nomogram comprising carcinoembryonic antigen, LNM, IL-35 and gp130 expression achieved better predictive accuracy compared with TNM stage for OS. Our data support that high IL-35 expression correlates with ICC aggressiveness and emerges as a valuable biomarker for evaluating ICC progression and prognosis in clinical work.

Prognostic Nomogram Based on Histological Characteristics of Fibrotic Tumor Stroma in Patients Who Underwent Curative Resection for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Fibrotic tumor stroma (FTS) has been implicated in cancer promotion in several neoplasms. The histological features of FTS are convenient and easily accessible in clinical routine in intrahepatic cholangiocarcinoma (ICC) specimens. The goal of this study was to explore prognostic impacts of the quantity and maturity of FTS on surgical ICC patients. Moreover, we aimed to propose an efficient prognostic nomogram for postoperative ICC patients. MATERIALS AND METHODS: The clinical profiles of 154 consecutive postoperative ICC patients were retrospectively analyzed. Tumor-stroma ratio and morphological maturity of FTS were evaluated on hematoxylin and eosin-stained tumor sections. CD3, CD8, and α-smooth muscle actin (α-SMA) staining were performed on corresponding tissue microarrays. The nomogram was established on variables selected by multivariate analyses and was validated in 10-fold cross-validation. RESULTS: Rich tumor stroma and strong α-SMA expression were associated with poor overall survival (OS). However, in multivariate analyses, these two biomarkers failed to stratify both OS and recurrence-free survival (RFS). Immature FTS was correlated with tumor multiplicity, advanced clinical stage, and sparser CD3 and CD8 positive tumor-infiltrating lymphocytes (TILs) and was identified as an independent prognostic indicator for both OS and RFS. The nomogram comprising FTS maturity, tumor number, microvascular invasion, and lymph node metastasis possessed higher predictive power relative to conventional staging systems. CONCLUSION: Immature FTS was an independent risk factor for survival and was associated with sparser CD3 and CD8 positive TILs in ICC. The prognostic nomogram integrating the maturity of FTS offers a more accurate risk stratification for postoperative ICC patients. IMPLICATIONS FOR PRACTICE: Accumulating evidence has suggested that fibrotic components in tumor microenvironment (TME) play a complicated and vital role in TME reprogramming and cancer progression. However, in clinical practice, the evaluation of fibrotic tumor stroma (FTS) is still neglected to some extent. This study's findings indicated that, in intrahepatic cholangiocarcinoma (ICC), the histological maturity of FTS is a robust prognostic indicator for patients who underwent curative resection. Moreover, prognostic nomogram constructed on the maturity of FTS possessed higher predictive power relative to the conventional tumor-node-metastasis staging systems. Taken together, the evaluation of FTS should be emphasized in clinical routine for more accurate prognostic prediction in postoperative ICC patients.

A novel and validated prognostic nomogram based on liver fibrosis and tumor burden for patients with hepatocellular carcinoma after curative resection.

BACKGROUND AND OBJECTIVES: Most conventional staging systems were formulated concerning the tumor burden rather than the severity of liver fibrosis, which plays a central role in tumor promotion. The aim of this study was to formulate a prognostic nomogram comprehensively considering these two aspects for HCC after hepatectomy. METHODS: The prognostic significances of the four indicators namely laminin, hyaluronic acid, human procollagen type-III, and collagen type-IV that reflect liver fibrosis were explored in two independent cohorts. A nomogram was established based on the results of multivariate analysis. The predictive accuracy of the nomogram was measured by concordance index (C-index) and calibration. The decision curve analysis (DCA) was used to evaluate the clinical benefit of the nomogram. RESULTS: Preoperative serum laminin level is an independent prognostic factor for overall survival in HCC patients after resection. The C-indices of the nomogram in the training and validation cohorts were 0.779 and 0.719, respectively. The calibration showed optimal agreement between the prediction by nomogram and actual observation. Moreover, the C-indices and DCA revealed that the nomogram provided better clinical benefit compared with the BCLC stage, CLIP score, and AJCC 7th edition. CONCLUSIONS: The prognostic nomogram constructed on laminin represents a superior predictive model.

New nomogram predicts the recurrence of hepatocellular carcinoma in patients with negative preoperative serum AFP subjected to curative resection.

BACKGROUND: There is currently no established model for predicting the recurrence of hepatocellular carcinoma (HCC) in patients with negative alpha-fetoprotein (AFP) after curative resection. Therefore, the objective of this study was to establish a nomogram to identify the risk of recurrence in AFP-negative (

S100A11 promotes TGF-ß1-induced epithelial-mesenchymal transition through SMAD2/3 signaling pathway in intrahepatic cholangiocarcinoma.

AIM: Our previous study found S100A11 was significantly raised in intrahepatic cholangiocarcinoma cells, but the relationship between S100A11 and intrahepatic cholangiocarcinoma remains unclear. METHODS: We investigated the effect of silencing S100A11 on TGF-ß1-induced epithelial-mesenchymal transition (EMT), cell migration and invasion. RESULTS: Our results demonstrated silencing S100A11 inhibited TGF-ß1-induced cell migration, invasion and EMT, expression of EMT markers E-cadherin, N-cadherin, ß-catenin, vimentin, Slug and Snail was reversed. Furthermore, TGF-ß1-induced p-SMAD2 and 3 were also inhibited due to low S100A11 expression. CONCLUSION: Our present study indicated that S100A11 promotes EMT through accumulation of TGF-ß1 expression, and TGF-ß1-induced upregulation of p-SMAD2 and 3.

Prognostic Nomograms Stratify Survival of Patients with Hepatocellular Carcinoma Without Portal Vein Tumor Thrombosis After Curative Resection.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma (HCC) without portal vein tumor thrombosis (PVTT) after curative resection is at variance. We identified the risk factors of poor postoperative prognosis and consequently developed prognostic nomograms generating individual risk of death and recurrence for this subgroup of patients with HCC. METHODS: The risk factors were identified and nomograms were developed based on a retrospective study of 734 patients in the primary cohort who underwent curative resection for HCC from 2010 to 2012. The predictive accuracy and discriminative ability of the nomograms were determined by concordance index (C-index) and calibration curve and compared with traditional staging systems of HCC. The results were validated in an independent cohort of 349 patients operated at the same institution in 2007. RESULTS: All of the independent factors for survival in multivariate analysis in the primary cohort were selected into the nomograms. The calibration curve for probability of survival showed good agreement between prediction by nomograms and actual observation. The C-indices of the nomograms for predicting overall survival and recurrence-free survival were 0.755 (95% confidence interval [CI], 0.752-0.758) and 0.665 (95% CI, 0.662-0.668), respectively, which were statistically higher than the C-indices of other HCC prognostic models. The results were further confirmed in the validation cohort. CONCLUSION: The proposed nomograms resulted in more accurate prognostic prediction for patients with HCC without PVTT after curative resection. The Oncologist 2017;22:561-569 IMPLICATIONS FOR PRACTICE: Hepatocellular carcinoma (HCC) poses a great therapeutic challenge due to the poor prognosis in patients underwent surgical resection. The portal vein tumor thrombosis (PVTT) as a robust risk factor for survival has been routinely integrated to staging systems. Nonetheless, the prognosis stratification for patients without PVTT was neglected to some extent. Herein, independent risk factors of OS and RFS in HCC patients without PVTT were reconfirmed. A predictive nomogram was constructed on these risk factors and was demonstrated to be a more accurate predictive model in HCC patients without PVTT, compared with the traditional staging systems.

S100A6 promotes proliferation of intrahepatic cholangiocarcinoma cells via the activation of the p38/MAPK pathway.

AIM: We explored the expression of S100A6 and its role in intrahepatic cholangiocarcinoma (ICC). METHODS: The expression of S100A6 in ICC samples was detected by immunohistochemistry. In vitro experiments, we silenced and overexpressed S100A6 to investigate its role in cell functions. RESULTS: The expression of S100A6 was markedly increased in ICC tissues and cell lines. S100A6 overexpression was an independent risk factor for patients' survival. Silencing S100A6 resulted in a suppression of proliferation and p38/MAPK activity, while overexpressing S100A6 caused a promotion of proliferation and p38/MAPK. DISCUSSION:  S100A6 participated in the proliferation of ICC cells and correlated with a more aggressive behavior of ICC. Conclusion: S100A6 may serve as a novel prognostic marker and a potential therapeutic target for ICC patients.

Hysteroscopic Curettage Followed by Megestrol Acetate Plus Metformin as a Fertility-Sparing Treatment for Women with Atypical Endometrial Hyperplasia or Well-Differentiated Endometrioid Endometrial Carcinoma.

Background: In reproductive-aged women, the incidence of atypical endometrial hyperplasia (AEH) or endometrioid endometrial carcinoma (EEC) is rising globally. The study aimed to investigate the effectiveness of hysteroscopic curettage followed by megestrol acetate (MA) plus metformin as conservative treatment in AEH and early EEC. Methods: We retrospectively studied AEH and stage IA, grade 1 EEC patients treated with hysteroscopic curettage followed by MA (160 mg/d) plus metformin (1500 mg/d) from January 2010 to December 2020 at Fudan University Shanghai Cancer Center. Treatment outcomes were assessed by complete response (CR) rate, recurrence rate, and pregnancy outcomes. Univariate and multivariate analyses were performed via the logistic regression model. Results: The study included 79 patients, 31 (39.2%) with AEH and 48 (60.8%) with EEC. The medians of age (years) and follow-up time (months) were 30 and 39.5, respectively. Seventy-six patients (96.2%) finally achieved CR. The median time to CR was 3.6 (3.0-20.6) months. The CR rate after 3 months, 6 months, and 1 year was 55 (69.6%), 67 (84.8%), and 72 (91.1%), respectively. Recurrence occurred in 26 (34.2%) patients. Treatment duration ⩾9 months was associated with a lower recurrence rate after CR (P = .012). Fourteen (93.3%) of the 15 recurrent patients who received progestin re-treatment achieved CR again. Finally, 29 patients delivered live births. Conclusions: Hysteroscopy followed by MA plus metformin can achieve CR in short time and is overall safe. Consolidation treatment should be prolonged to decrease the recurrence rate, despite a shorter time to CR.

Extracellular vesicle-derived miR-320a targets ZC3H12B to inhibit tumorigenesis, invasion, and angiogenesis in ovarian cancer.

Extracellular vesicles (EVs) play crucial roles in intercellular communication. miRNAs derived from EVs emerge as promising diagnostic indicators and therapeutic targets in a variety of malignancies. Tremendous studies have revealed the function of miRNAs derived from EVs in tumorigenesis, metastasis and other aspects. The mechanism of action of EV-derived miRNAs, however, in ovarian cancer remains largely unknown. In this study, EVs were enriched from the ovarian cancer cell lines. EVs as a whole could promote cell proliferation, invasion and new vasculature formation. However, the down-regulated EV-derived miR-320a was demonstrated to potentially suppress tumorigenesis, metastasis and angiogenesis. Moreover, EV-derived miR-320a has been proved to directly regulate a previously unknown target, ZC3H12B. An unreported role of ZC3H12B in promoting ovarian cancer cell proliferation has been elucidated and miR-320a could mediate the expression of ZC3H12B, thereby inhibiting the downstream response. As for the practical clinic values, lower expression of EV-derived miR-320a correlates with shorter survival period, indicating that EV-derived miR-320a may also serve as a prognostic biomarker in ovarian cancer. This research provides new insight into the molecular mechanism of EV-derived miR-320a in ovarian cancer and may provide new therapeutic and prognostic strategies for ovarian cancer treatment.

Comprehensive Analysis of the Prognosis and Correlations With Immune Infiltration of S100 Protein Family Members in Hepatocellular Carcinoma.

S100 protein family members (S100s) are commonly dysregulated in various tumors including hepatocellular carcinoma (HCC). However, the diverse expression, mutation, prognosis and associations with immune infiltration of S100s in HCC have yet to be analyzed. Herein we investigated the roles of S100s in HCC from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas, Kaplan-Meier Plotter, cBioPortal and TIMER databases. Compared with para-cancer tissues, the expression levels of S100A4/S100A6/S100A10/S100A11/S100A13/S100A14/S100P were higher in HCC tissues, while the expression levels of S100A8/S100A9/S100A12 were decreased in tumor tissues. The mRNA levels of S100A2/S100A7/S100A7A/S100A8/S100A9/S100A11 were correlated with advanced tumor stage. Besides, higher mRNA expressions of S100A6/S100A10/S100A11/S100A13/S100A14/S100P were shown to have shorter overall survival (OS), while higher expression of S100A12 was associated with favorable OS. Further, the mutation rate of S100s was investigated, and the high mutation rate (53%) was associated with shorter OS. Additionally, the expressions of S100s were found to be significantly associated with various immune infiltrating cells. Hence, our results showed that S100A6/S100A10/S100A11/S10012/S100A13/S100A14/S100P may be regarded as new prognostic or therapeutic markers and S100s inhibitors may be helpful in the combination of immunotherapies.

Hepatic stellate cells promote intrahepatic cholangiocarcinoma progression via NR4A2/osteopontin/Wnt signaling axis.

Intrahepatic cholangiocarcinoma (ICC) is a highly fatal malignancy characterized by a vast amount of intra-tumoral fibroblasts. These fibroblasts are potentially implicated in maintaining the high aggressiveness of ICC, whereas its pro-cancer mechanisms remain scarcely reported. Here, by establishing co-culture models of ICC cells and hepatic stellate cells (HSCs), we identified that HSCs triggered the expression of nuclear receptor family 4 subgroup A member 2 (NR4A2), a transcription factor previously reported as a molecular switch between inflammation and cancer, in ICC cells. Functionally, NR4A2 promotes tumor proliferation, metastatic potentiality and represents an independent prognostic indicator for overall survival in ICC patients. Mechanistically, NR4A2 upregulates osteopontin (OPN) expression through transcriptional activation and thereby augments the activity of Wnt/ß-catenin signaling. Intriguingly, in the context of co-culture, vascular endothelial growth factor (VEGF), a previously proved NR4A2 stimulus, not only enhances NR4A2 expression, but also can be blunted by the interference of the NR4A2-OPN axis. Altogether, this study suggests the NR4A2/OPN/Wnt signaling axis to be a pivotal executor of HSC-instigated cancer-promoting roles in ICC, and the NR4A2/OPN/VEGF positive feedback loop may help to reinforce the effect.

Comparative performance of inflammation-based prognostic scores in patients operated for intrahepatic cholangiocarcinoma.

OBJECTIVE: Prognostic performance of inflammation-based prognostic scores, including the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI) has been explored in patients with varied types of cancer, though little data is available in intrahepatic cholangiocarcinoma (ICC). This study sought to evaluate the impact of systemic inflammation on the overall survival (OS) of ICC patients, and to identify more optimal prognostic indices. PATIENTS AND METHODS: The prognostic power of all the scores mentioned above was compared in 123 patients underwent curative surgery for ICC using Kaplan-Meier curves, COX regression models and the receiver operating characteristics (ROC) curves. The results were validated in a cohort of 95 ICC patients. RESULTS: Multivariate analysis identified LMR as the only independent inflammation-based predictor for OS in the training cohort (P=0.007, HR 2.082, 95% CI 1.218-3.558). More importantly, the combined score of LMR and pTNM designated the inflammation-based pathological stage (IPS) outperformed other established scores in terms of discriminatory ability, monotonicity and homogeneity in the training and validation cohorts. CONCLUSION: This study reveals that preoperative LMR is an independent predictor of OS in ICC patients after hepatectomy, and the IPS can be applied as a novel prognostic indicator in these patients.

High expression of Oct4 and Nanog predict poor prognosis in intrahepatic cholangiocarcinoma patients after curative resection.

Oct4 and Nanog are reported to promote tumor progression in several cancers, but the effect on intrahepatic cholangiocarcinoma (ICC) is unknown. The aim of our present study was to explore the prognostic role of Oct4 and Nanog on patients with ICC. Immunohistochemistry was used to detect the expression of Oct4 and Nanog in a random cohort of 116 ICC patients, and validated in another independent cohort of 103 patients. Prognostic nomograms were formulated for OS and RFS prediction of ICC patients. Our results showed Oct4 and Nanog highly expressed in ICC tumor tissues and were identified as independent prognostic factors for patients' OS and RFS. Significant positive correlation was found between Oct4 and Nanog expression. Co-expression of Oct4 and Nanog implied the poorest OS and RFS in ICC patients. Our nomograms comprising Oct4 and Nanog achieved better predictive accuracy in training and validation cohorts compared with AJCC 7th edition and LCSGJ stage for OS and RFS prediction. Our study support the high expression of Oct4 and Nanog in ICC implies aggressive tumor behaviors and suggest a poor clinical prognosis, which emerges as valuable biomarkers for identifying patients at high risk after curative resection.

HHLA2 in intrahepatic cholangiocarcinoma: an immune checkpoint with prognostic significance and wider expression compared with PD-L1.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. This study aimed to investigate whether HHLA2, a newly identified B7 family immune checkpoint for T cells, could be a therapeutic target next to PD-L1 in ICC. METHODS: Expression levels of PD-L1 and HHLA2 as well as infiltrations of CD3+, CD8+, CD4 + Foxp3+, CD68+, CD163+ and CD20+ cells were evaluated by immunohistochemistry in 153 resected ICC samples. Comprehensive comparisons were made between PD-L1 and HHLA2 in terms of the expression rates, clinicopathological features and infiltrations of different immune cells. The expression level and prognostic significance of HHLA2 were further validated in an independent cohort. RESULTS: Expression of HHLA2 is more frequent than PD-L1 in ICC (49.0% vs 28.1%). Co-expression of both immune checkpoints was infrequent (13.1%) and 50% PD-L1 negative cases were with elevated HHLA2. HHLA2 overexpression was associated with sparser CD3+ tumor infiltrating lymphocytes (TILs), CD8+ TILs and a higher CD4 + Foxp3+/CD8+ TIL ratio, whereas PD-L1 expression was associated with prominent T cells and CD163+ tumor associated macrophages infiltrations. PD-L1 failed to stratify overall survival (OS) but HHLA2 was identified as an independent prognostic indicator for OS in two independent cohorts. CONCLUSIONS: Compared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients.

Fibrinogen and C-reactive protein score is a prognostic index for patients with hepatocellular carcinoma undergoing curative resection: a prognostic nomogram study.

Background: While curative resection is the established strategy for Hepatocellular carcinoma (HCC) patients, the prognosis still remains poor, and the efficiency of existing prediction models is unsatisfactory. Therefore, we aimed to develop a credible and easy-to-use prognostic index for patients with HCC undergoing curative therapy. Methods: A total of 768 patients with HCC, who underwent curative resection from December 2010 to June 2012 in Zhongshan Hospital, were divided into a training cohort with 616 patients and a validating cohort of 152 patients at a ratio of 4 to 1 by random allocation. Then, a retrospective cohort study was conducted to identify effective prognostic indexes. Results: FC-score, which incorporates fibrinogen and C-reactive protein, was established. In the multivariate analysis for OS and RFS, FC-score has shown to be a significant independent prognostic index in both the training cohort and validation cohort. Furthermore, the C-index of the FC-score for OS and RFS were 0.698 and 0.594 respectively, which were superior to other inflammation systems such as IBI, IBS, and GPS. Then, we developed a novel nomogram, which integrated FC-score into the conventional BCLC staging system. This new nomogram gave rise to a new C-index of 0.746 (95%CI: 0.743-0.749) for OS, and 0.654 (95%CI: 0.652-0.656) for RFS. The calibration curve and decision curve analysis indicated that our nomogram was highly consistent between predicted and actual observations. Conclusions: FC-score represents a novel, convenient, reliable, and accurate prognostic predictor for both OS and RFS in HCC patients undergoing curative therapy.

Prognostic impact of lactic dehydrogenase to albumin ratio in hepatocellular carcinoma patients with Child-Pugh I who underwent curative resection: a prognostic nomogram study.

BACKGROUND: Radical resection is the treatment of choice for hepatocellular carcinoma (HCC). However, even with this treatment, HCC prognosis and the efficacy of current predictive models for such patients remain unsatisfactory. Here, we describe an accurate and easy-to-use prognostic index for patients with HCC who have undergone curative resection. METHODS: The study population comprised of 1,041 patients with HCC who underwent curative resection at Zhongshan Hospital. This population was reduced to 768 patients who were treated in 2012 analyzed as the training cohort and 273 patients treated in 2007 who were used as a validation cohort. RESULTS: The lactic dehydrogenase to albumin ratio (LAR) was identified as a significant prognostic index for both overall survival and recurrence-free survival in two independent cohorts. The optimal cutoff value for LAR was determined to be 5.5. The C-index of LAR was superior to other inflammatory scores and serum parameters. This biomarker was also shown to be a stable predictive index in the validation cohort. The new nomogram combining LAR with the Barcelona Clinic Liver Cancer staging system had an improved ability to discriminate overall survival and recurrence-free survival. Nomogram predictions were consistent with observations based on calibration and decisive curve analysis in both independent cohorts. CONCLUSION: LAR is a novel, convenient, reliable, and accurate prognostic predictor in patients with HCC undergoing curative resection. Our results suggest the recommendation of LAR to be used in routine clinical practice.

Treatment with the herbal formula Songyou Yin inhibits epithelial-mesenchymal transition in hepatocellular carcinoma through downregulation of TGF-ß1 expression and inhibition of the SMAD2/3 signaling pathway.

It was previously reported that treatment with the herbal formula Songyou Yin (SYY) may serve a role in attenuating epithelial-mesenchymal transition (EMT). In the present study, the effect of treatment with SYY on transforming growth factor-ß1 (TGF-ß1)-induced EMT was investigated and the potential underlying molecular mechanisms were evaluated. MHCC97H cells were pretreated with SYY for 4 weeks and subsequently named MHCC97HSYY cells. Simultaneously, MHCC97H cells were cultured for 4 weeks without SYY and used as a negative control. Western blot analysis and enzyme-linked immunosorbent assays demonstrated that treatment with SYY inhibited EMT-associated changes and TGF-ß1 expression in MHCC97H cells. MHCC97H and MHCC97HSYY cells were treated with 10 ng/ml TGF-ß1 to induce EMT. The results of the present study demonstrated that pretreatment with SYY markedly inhibited TGF-ß1-induced morphological changes, and reversed the expression of the EMT markers E-cadherin and N-cadherin. In addition, expression levels of the TGF-ß1 downstream proteins, phosphorylated mothers against decapentaplegic homologs (p-SMAD)2 and 3, were reduced. Transwell assays indicated that pretreatment with SYY inhibited TGF-ß1-induced cancer cell invasion and migration. The results of the present study indicate that SYY inhibited EMT through attenuation of TGF-ß1 expression, and downregulation of p-SMAD2 and 3.

Prognostic significance of serum procalcitonin in patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization: A retrospective analysis of 509 cases.

Although procalcitonin (PCT) is a valid marker for early diagnosis of bacterial infections, its accuracy in hepatocellular carcinoma (HCC) patients is unknown. The aim of this study was to investigate the prognostic significance of PCT in patients with unresectable HCC treated with transcatheter arterial chemoembolization (TACE).A total of 509 patients with unresectable HCC initially treated with TACE were enrolled in this retrospective study. According to quartile of the PCT values, all patients were divided into 4 groups. Overall survival (OS) was evaluated with the Kaplan-Meier method. Significant difference was estimated with the Log rank method. Univariate and multivariate analyses were used for evaluating the significance of the prognostic factor.The median follow-up period was 18 months and there were significant differences in the survival rates between the 4 groups. The HR (95% CI) for all-cause mortality comparing patients with PCT Quartile2-4 to patient with Quartile1 (HR = 1.00) were 1.353 (1.023-1.791), 1.799 (1.354-2.390), 1.960 (1.455-2.639), respectively, (P < .001). PCT level was an important prognostic factor for predicting the prognosis of patients with unresectable HCC treated with TACE.