scholarly journals Impact of Angiogenesis- and Hypoxia-Associated Polymorphisms on Tumor Recurrence in Patients with Hepatocellular Carcinoma Undergoing Surgical Resection

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3826
Author(s):  
Hannah Miller ◽  
Zoltan Czigany ◽  
Isabella Lurje ◽  
Sophie Reichelt ◽  
Jan Bednarsch ◽  
...  

Tumor angiogenesis plays a pivotal role in hepatocellular carcinoma (HCC) biology. Identifying molecular prognostic markers is critical to further improve treatment selection in these patients. The present study analyzed a subset of 10 germline polymorphisms involved in tumor angiogenesis pathways and their impact on prognosis in HCC patients undergoing partial hepatectomy in a curative intent. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained from 127 HCC patients at a German primary care hospital. Genomic DNA was extracted, and genotyping was carried out using polymerase chain reaction (PCR)–restriction fragment length polymorphism-based protocols. Polymorphisms in interleukin-8 (IL-8) (rs4073; p = 0.047, log-rank test) and vascular endothelial growth factor (VEGF C + 936T) (rs3025039; p = 0.045, log-rank test) were significantly associated with disease-free survival (DFS). After adjusting for covariates in the multivariable model, IL-8 T-251A (rs4073) (adjusted p = 0.010) and a combination of “high-expression” variants of rs4073 and rs3025039 (adjusted p = 0.034) remained significantly associated with DFS. High-expression variants of IL-8 T-251A may serve as an independent molecular marker of prognosis in patients undergoing surgical resection for HCC. Assessment of the patients’ individual genetic risks may help to identify patient subgroups at high risk for recurrence following curative-intent surgery.

2018 ◽  
Vol 108 (1) ◽  
pp. 23-29
Author(s):  
J. Rhu ◽  
G. S. Choi ◽  
J. M. Kim ◽  
C. H. D. Kwon ◽  
S. J. Kim ◽  
...  

Background and Aims: This study was designed to analyze the feasibility of laparoscopic right posterior sectionectomy compared to laparoscopic right hemihepatectomy in patients with hepatocellular carcinoma located in the posterior segments. Material and Methods: The study included patients who underwent either laparoscopic right posterior sectionectomy or laparoscopic right hemihepatectomy for hepatocellular carcinoma located in segment 6 or 7 from January 2009 to December 2016 at Samsung Medical Center. After 1:1 propensity score matching, patient baseline characteristics and operative and postoperative outcomes were compared between the two groups. Disease-free survival and overall survival were compared using Kaplan–Meier log-rank test. Results: Among 61 patients with laparoscopic right posterior sectionectomy and 37 patients with laparoscopic right hemihepatectomy, 30 patients from each group were analyzed after propensity score matching. After matching, baseline characteristics of the two groups were similar including tumor size (3.4 ± 1.2 cm in laparoscopic right posterior sectionectomy vs 3.7 ± 2.1 cm in laparoscopic right hemihepatectomy, P = 0.483); differences were significant before matching (3.1 ± 1.3 cm in laparoscopic right posterior sectionectomy vs 4.3 ± 2.7 cm in laparoscopic right hemihepatectomy, P = 0.035). No significant differences were observed in operative and postoperative data except for free margin size (1.04 ± 0.71 cm in laparoscopic right posterior sectionectomy vs 2.95 ± 1.75 cm in laparoscopic right hemihepatectomy, P < 0.001). Disease-free survival (5-year survival: 38.0% in laparoscopic right posterior sectionectomy vs 47.0% in laparoscopic right hemihepatectomy, P = 0.510) and overall survival (5-year survival: 92.7% in laparoscopic right posterior sectionectomy vs 89.6% in laparoscopic right hemihepatectomy, P = 0.593) did not differ between the groups based on Kaplan–Meier log-rank test. Conclusion: For hepatocellular carcinoma in the posterior segments, laparoscopic right posterior sectionectomy was feasible compared to laparoscopic right hemihepatectomy when performed by experienced laparoscopic surgeons.


2021 ◽  
Author(s):  
João Paulo Maciel Silva ◽  
Fabricio Ferreira Coelho ◽  
Alex Jones Flores Cassenote ◽  
Vagner Birk Jeismann ◽  
Gilton Marques Fonseca ◽  
...  

Abstract Background Recent studies from eastern centers have demonstrate an association between inflammatory response and long-term outcomes after hepatocellular carcinoma (HCC) resection. However, the prognostic impact of inflammatory markers in western patients, with distinct tumor and epidemiologic features, is still unknown. Aim To evaluate the prognostic impact of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), as well as their impact according to tumor size (< 5 cm, 5-10 cm, > 10 cm) in patients undergoing HCC resection with curative intent. Methods Optimal cut-off values for NLR, PLR, and MLR were determined by plotting the receiver operator curves. Overall survival (OS) and disease-free survival (DFS) curves were calculated using the Kaplan-Meier method and compared using the log-rank test. The Cox method was used to identify independent predictors of OS and DFS. Results In total, 161 consecutive adult patients were included. A high NLR (>1.715) was associated with worse OS (P=0.018). High NLR (>2.475; P=0.047) and PLR (>100.25; P=0.028) were predictors of short DFS. In HCC < 5 cm, MLR (>1.715) was associated with worse OS (P=0.047). In the multivariate analysis, high PLR was an independent predictor of worse DFS (hazard ratio [HR]=3.029; 1.499-6.121; P=0.002). Conclusions Inflammatory markers are useful tools to predict long-term outcomes after liver resection in western patients, high NLR was able to stratify subgroups of patients with short OS and DFS, an increased PLR was an independent predictor of short DFS, while high MLR was associated with short OS in patients with early HCC.


2020 ◽  
pp. 1-12
Author(s):  
Yongjin Wang ◽  
Yadi Liao ◽  
Wenwu Liu ◽  
Yuanping Zhang ◽  
Yichuan Yuan ◽  
...  

<b><i>Background and Aims:</i></b> Whether surgical resection or repeated ablation should be recommended for intrahepatic recurrent hepatocellular carcinoma (HCC) conforming to the Milan criteria after initial ablation remains unclear. In this study, we compared the outcomes of patients who underwent surgical resection with those who underwent re-ablation for recurrent HCC after initial curative-intent ablation. <b><i>Methods:</i></b> The data of 28 and 98 patients who underwent surgical resection and re-ablation, respectively, for recurrent HCC after initial ablation between January 2003 and 2017 were analyzed using propensity score matching. <b><i>Results:</i></b> Before matching, the 1-, 3-, and 5-year overall survival (OS) rates were 95.7, 83.0, and 74.4% for the ablation group, compared to 92.9, 89.1, and 70.9% for the resection group (<i>p</i> = 0.490). The corresponding disease-free survival (DFS) rates were 67.5, 40.1, and 25.6% for the ablation group and were 85.4, 59.9, and 53.3% for the resection group (<i>p</i> = 0.018). After matching, the 1-, 3-, and 5-year OS rates for the ablation and resection group were 95.2, 85.5 and 81.8% versus 96.0, 96.0, and 76.4%, respectively (<i>p</i> = 0.550). The 1-, 3-, and 5-year DFS rates were 58.0, 39.5, and 29.9% for the ablation group and were 95.8, 67.2, and 59.8% for the resection group (<i>p</i> = 0.004). Cox proportional hazards model identified surgical resection as the only significant prognostic factor for DFS but not for OS. <b><i>Conclusion:</i></b> For intrahepatic recurrent HCC patients after initial ablation, surgical resection could provide better DFS than re-ablation, while no difference in OS was observed between the 2 treatment groups.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Chen Yu ◽  
Xiang-Yi Chen ◽  
Xin Li ◽  
Hai-Yu Zhou ◽  
De-Quan Yu ◽  
...  

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.


Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 217-223
Author(s):  
Xin Song ◽  
Shidong Zhang ◽  
Run Tian ◽  
Chuanjun Zheng ◽  
Yuge Xu ◽  
...  

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chih-Wen Lin ◽  
Tsung-Chin Wu ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Pei-Min Hsieh ◽  
...  

Abstract Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.


2021 ◽  
Author(s):  
Tingdan Zheng ◽  
Wuqi Song ◽  
Aiying Yang

Abstract Objective Here we performed the Bioinformatics analysis on the data from The Cancer Genome Atlas (TCGA), in order to find the correlation between the expression of ATP Binding Cassette (ABC) Transporters’ genes and hepatocellular carcinoma (HCC) prognosis; Methods Transcriptome profiles and clinical data of HCC were obtained from TCGA database. Package edgeR was used to analyze differential gene expression. Patients were divided into low-ABC expression and high-ABC expression groups based on the median expression level of ABC genes in cancer. The overall survival and short-term survival (n= 341) of the two groups was analyzed using the log-rank test and Wilcoxon test; Results We found that ABC gene expression was correlated with the expression of PIK3C2B (p<0.001, ABCC1: r=0.27; ABCC10: r=0.57; ABCC4: r=0.20; ABCC5: r=0.28; ABCB9: r=0.17; ABCD1: r=0.21). All patients with low-ABC expression showed significantly increased overall survival. Significantly decreased overall survival (Log-rank test: p<0.05, Wilcoxon test: p<0.05) was found in patients with high expression of ABCC1 (HR=1.58), ABCD1 (HR=1.45), ABCC4 (HR=1.56), and ABCC5 (HR=1.64), while decreased short-term survival (Log-rank test: p>0.05, Wilcoxon test: p<0.05) was correlated with the increased expression of ABCC10 (HR=1.29), PIK3C2B (HR=1.29) and ABCB9 (HR=1.23); Conclusions Our findings indicate that the specific ABC gene expression correlates with the prognosis of HCC. Therefore, ABC expression profile could be a potential indicator for HCC patients.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Qiu-shuang Wang ◽  
Liang-Liang Shi ◽  
Fei Sun ◽  
Yi-fan Zhang ◽  
Ren-Wang Chen ◽  
...  

Objective. Accumulating evidence suggests that pseudogenes play potential roles in the regulation of their cognate wild-type genes, oncogenes, and tumor suppressor genes. ANXA2P2 (annexin A2 pseudogene 2) is one of three pseudogenes of annexin A2 that have recently been shown to be aberrantly transcribed in hepatocellular carcinoma (HCC) cells. However, its clinical meaning and biological function in HCC have remained unclear. Therefore, the present study was aimed at exploring the prognostic value of a high expression of ANXA2P2 in HCC tissue and at identifying whether it can affect the efficacy of targeted drugs (sorafenib, regorafenib, and lenvatinib). Methods. We obtained ANXA2P2 mRNA expression levels from The Cancer Genome Atlas (TCGA) RNA sequence database. The expression levels of ANXA2P2 in 49 pairs of intratumoral and peritumoral liver tissues were examined by RT-PCR. Wound healing and transwell assays were performed to confirm the tumor-promoting properties of ANXA2P2 in HCC cells. CCK8 assay was conducted to identify whether ANXA2P2 can affect the growth of HCC cells when administered with targeted drugs (sorafenib, regorafenib, and lenvatinib). Results. The expression of ANXA2P2 in HCC tissues was significantly higher than that in adjacent cancerous tissues from TCGA database and validation group. Additionally, patients with high ANXA2P2 expression in HCC tissue had a shorter overall survival, whereas no statistically significant correlation was found between ANXA2P2 expression and disease-free survival (p=0.08) as well as other clinical parameters, such as age, gender, histological grade, T classification, stage, albumin level, alpha-fetoprotein, and vascular invasion (p=0.7323, 0.8807, 0.5762, 0.8515, 0.7113, 0.242, 1.0000, and 0.7685, respectively). Furthermore, in vitro experiments showed that knockdown of ANXA2P2 inhibited migration and invasion of HCC cells but did not have an influence on the HCC cell proliferation when treated with targeted drugs (sorafenib, regorafenib, and lenvatinib). Conclusion. Our study confirmed elevated ANXA2P2 expression levels in HCC tissue compared with adjacent noncancerous tissue and a worse prognosis of patients with high ANXA2P2 levels in the HCC tissue. The newly found properties of promoting migration and invasion of ANXA2P2 in HCC help to explain this phenomenon. ANXA2P2 could be a novel and suitable predicative biomarker for the risk assessment of recurrence or metastasis of HCC patients but may not be effective to predict the efficacy of targeted drugs.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 246-246
Author(s):  
Marieke Pape ◽  
Pauline A.J. Vissers ◽  
Laurens Beerepoot ◽  
Mark I. Van Berge Henegouwen ◽  
Sjoerd Lagarde ◽  
...  

246 Background: Among patients with potentially curable esophageal cancer (EC) or gastroesophageal junctional cancer (GEJC) treated with curative intent, survival remains poor and around half of these patients have disease recurrence within a few years. This study addresses the need for real-world data on disease-free survival (DFS) and overall survival (OS) in patients with EC or GEJC who underwent potentially curative treatment. Methods: Patients selected from the nationwide Netherlands cancer registry (NCR) had received a primary diagnosis of non-metastatic EC or GEJC (excluding patients with T4b tumors) in 2015 or 2016 and received treatment with curative intent. Curative intent was defined as receiving resection (with or without [neo]adjuvant therapy) or definitive chemoradiotherapy (dCRT) without surgery. DFS and OS were analysed using Kaplan-Meier curves with Log-Rank test from resection date or end of dCRT. A sub-analysis was performed for NCR patients selected to align with the population of the CheckMate-577 phase 3 study of adjuvant nivolumab, i.e. patients with non-cervical stage II/III disease, R0 resection and residual pathological disease after neoadjuvant CRT (nCRT) and surgery. Results: We identified 1916 patients of median age of 67 years and predominantly male (76%). The majority (79%) received surgery and 21% of patients received dCRT. In resected patients, 83% received nCRT, 10% neoadjuvant chemotherapy (with or without adjuvant CRT) and 7% received no (neo)adjuvant treatment. Compared to the resected group, the population receiving dCRT had significantly fewer males (65% vs 78%), a higher median age (72 vs 65 years) and worse performance status. Patients receiving dCRT significantly shorter median DFS (14.2 months) and OS (20.9 months) compared to resected patients (DFS: 26.4 months, p < 0.001; OS: 40.5 months, p < 0.001). The 1- and 3-year DFS probabilities were 68% and 44%, respectively, in resected patients, and 56% and 24%, respectively, in patients receiving dCRT. In patients receiving nCRT followed by surgery, the median DFS and OS were 25.2 and 38.0 months, respectively, and 1- and 3-year DFS probabilities were 67% and 43%, respectively. In the sub-analysis (n = 725) the median DFS and OS were 19.2 and 29.4 months, respectively, and the 1- and 3-year DFS rates were 62% and 36%, respectively. Conclusions: Although patients are treated with curative intent, a considerable amount of patients with non-metastatic EC or GEJC experienced recurrence within two years. Resected patients had a higher DFS and OS compared to patients receiving dCRT.


2020 ◽  
Author(s):  
Jiao Yuan ◽  
Li Zeng ◽  
min tian ◽  
Sisi Chen ◽  
Huai yi Yao ◽  
...  

Abstract BackgroundHepatocellular carcinoma (HCC) ranks as the fourth most common cancer and the third leading cause of cancer-related mortality worldwide. With the development of minimally invasive surgical techniques, laparoscopic hepatectomy is becoming more prevalent in liver surgery. There are multiple reports to evaluate the safety and feasibility of laparoscopic liver resection. Unfortunately, the jury is still out on whether laparoscopic hepatectomy is better than open hepatectomy. The aim of this study is to compare the perioperative and postoperative long-term outcomes of open hepatectomy and laparoscopic hepatectomy for hepatocellular carcinoma, and to evaluate the safety and efficacy of the two surgical methods for hepatocellular carcinoma.MethodsA prospective cohort study of patients who underwent major hepatectomy for hepatocellular carcinoma between October 2017 and September2018 was performed. And these patients were followed for 24 months after surgery. There are158 patients involved in the present study and they were randomly divided into two groups, LH group (n=60), and OH group (n=98). And all of 158 patients underwent hepatectomy. Continuous data were compared by one-way ANOVA, and categorical data were compared by Fisher’s exact test or the c2 test. Survival curves were calculated by the Kaplan–Meier method and compared using the log-rank test. The study was approved by the ethics committee of Union Hospital. (No. WHUH2018S002) and registered in the International Clinical Trial Registry (No. NCT03585166). Informed consent was signed by all patients.ResultsIncision lengths of LH (5.14±3.11cm) were shorter than OH(20.92±6.44cm), P<0.001. Operating time of LH (398.53±170.51 minutes) were longer than OH(257.74±91.31 minutes), P=0.003. Hospital stay of LH(17.72±5.82 days) were shorter than OH(21.42±8.44 days), P<0.001. The average hospitalization costs of LH group (82741.18±26128.81¥) were significantly less than OH group (94998.75±30499.64¥), p=0.011<0.05. The incidence of total complications was also lower in LH group than in OH group (P<0.001). Postoperatively, the leukocyte was significantly lower at 1st day in LH group (9.79±2.92G/L) than in OH group (12.6±4.85 G/L), p<0.001.The aspartate aminotransferase (AST) was significantly lower at 7th day in LH group (39.25±16.63 U/L) than in OH group (62.49±67.77 U/L), p=0.01<0.05. The albumin was significantly higher at 3rd day in LH group (34.21±3.94 g/L) than in OH group (31.24±5.23 g/L), p<0.001. The albumin was significantly higher at 7th day in LH group (35.26±3.73 g/L) than in OH group (33.31±4.51 g/L), p=0.006<0.05. Direct bilirubin was significantly higher at 1st day in LH group (10.28±10.70 µmol /L) than in OH group (315.03±15.71 µmol /L), p=0.04<0.05. The follow-up time after surgery was 24 months (1-24). The mean follow-up time after surgery was 17.94±9.132. Log rank test was performed to compare overall survival rates between the two groups. There were no statistically significant differences with 2-year survival rate between LH and OH group for liver cancer patients, nor was disease-free survival.ConclusionsLaparoscopic hepatectomy surgery supplied a lower incision lengths, hospital stay and incidence of total complications. Laparoscopic hepatectomy was cheaper the open hepatectomy.There were no statistically significant differences with 2-year survival rate between the two group for liver cancer patients, nor was disease-free survival.


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