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Fengchun Mu,1,2,&ast; Bingjie Fan,1,&ast; Butuo Li,1 Wenru Qin,1 Haoqian Li,1,2 Chunni Wang,1 Bing Zou,1 Shijiang Wang,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 2Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 271016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626142, Fax +86-531-67626141, Email wanglinlinatjn@163.comPurpose: The present study aimed to evaluate the incidence rate of radiation pneumonitis (RP) in patients with advanced lung adenocarcinoma treated with first-generation (1G), second-generation (2G), or third-generation (3G) epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with thoracic radiotherapy (TRT).Patients and Methods: Patients with advanced lung adenocarcinoma simultaneously treated with 1G/2G/3G EGFR-TKIs and TRT between 2015– 2021 at Shandong Cancer Hospital and Institute were screened. The incidence rate of clinical and imaging RP was compared between the three groups.Results: A total of 200 patients treated with EGFR-TKIs were enrolled in this study, including 100 patients who were treated with 1G EGFR-TKIs, 50 patients who were treated with 2G EGFR-TKIs, and 50 patients who were treated with 3G EGFR-TKIs (patients matched in a 2:1:1 ratio for tumor characteristics). The overall incidence of clinical RP in the 1G, 2G, and 3G EGFR-TKI groups were 29%, 48%, and 28% (p=0.043), respectively, and that of imaging RP were 33%, 58%, and 36% (p=0.010), respectively. The incidence of RP with a clinical grade ≥ 3 in the three groups were 14%, 28%, and 12% (p=0.055), respectively, and that with an imaging grade ≥ 3 in the three groups were 11%, 32%, and 10% (p=0.002), respectively. The incidence of clinical RP was higher in the CFRT group than in the SBRT group, with an overall clinical grade of 38% vs 10% (p< 0.001) and imaging grade of 46% vs 10% (p< 0.001), respectively. In the multivariate analysis, only GTV volume was an independent predictive factor for all risks of clinical and imaging RP. V20 and grouping of 1G/2G/3G EGFR-TKIs were other independent predictive factors for the risk factors of RP for imaging grades.Conclusion: Compared with 2G EGFR-TKIs combined with TRT, 1G or 3G EGFR-TKIs combined with TRT achieved a lower incidence of RP.Keywords: EGFR-TKI, molecular targeted therapy, radiation pneumonitis, thoracic radiotherapy, lung adenocarcinoma

Yanan Duan,1,2 Wenru Qin,1,3 Linlin Yang,1,4 Bing Zou,1 Wenting Qie,1,3 Ruiting Song,1,2 Lu Xue,1,2 Linlin Wang1 1Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Weifang Medical University, Weifang, People’s Republic of China; 4Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Linlin Wang, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, Shandong, People’s Republic of China, Email wanglinlinatjn@163.comPurpose: We assess real-world outcomes, including safety and efficacy, of concurrent or sequential treatment with radiotherapy plus programmed cell death protein 1 (PD-1) inhibitors in patients with oligometastatic esophageal cancer (OMEC).Methods: This cohort study retrospectively collected clinical data of patients with synchronous or metachronous OMEC. All patients underwent concurrent or sequential treatment with radiotherapy plus PD-1 inhibitors. Each patient had up to five measurable metastatic lesions and up to three organs involved. Study endpoints were progression-free survival (PFS), treatment-related toxicities, locoregional progression-free survival (LRPFS), objective response rate (ORR), and disease control rate (DCR). Description statistics and Kaplan–Meier models were used for statistical analysis.Results: A total of 86 patients were included, most of whom were diagnosed with squamous cell carcinoma histology (98%) and presented with synchronous OMEC (64%). The median follow-up period was 17 months (range: 6– 32 months), the median PFS was 15.2 months (95% confidence interval: 12.1– 18.2 months); and the 1- and 2-year PFS rates were 61.4% and 26.7%, respectively. The 1- and 2-year LRPFS were 91.3% and 57.3%, respectively. The ORR and DCR were 46.5% and 91.8%, respectively. Forty-two patients (48.8%) experienced grade 3 or higher treatment-related adverse events (TRAEs); a grade 5 treatment-related adverse event was observed in one patient (1.2%) who died of immune-related pneumonitis.Conclusion: Combining radiotherapy with PD-1 inhibitors is a safe and effective treatment option for patients with OMEC. No new safety concerns were identified in this study. However, due to the potential risk of cumulative toxicity, an individual risk-benefit assessment for each patient is required prior to treatment initiation.Keywords: oligometastatic disease, esophageal cancer, PD-1 inhibitors, radiotherapy

Wenru Qin,1,2,&ast; Bing Zou,2,&ast; Xinyu Fan,2,3 Bingjie Fan,2 Shijiang Wang,2 Linlin Wang2 1Department of Oncology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Oncology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626142, Email wanglinlinatjn@163.comAbstract: The most common pathologic type of thymic carcinoma (TC) is squamous cell carcinoma (SCC). Small cell carcinoma is relatively rare, accounting for approximately 2% to 5% of all thymic tumors. Histologic transformation of TC has not yet been reported. Available treatments for TC patients who progress after first-line therapy are limited, which contributes to their poor prognosis. We reported an extraordinary case of a 66-year-old man who was diagnosed with thymic small cell carcinoma that transformed into SCC after third-line treatment. Surprisingly, the patient had a progression-free survival (PFS) of 25 months and an overall survival (OS) of 10 years on anlotinib as fourth-line therapy. The tolerance was well. Thus, anlotinib may be a safe and promising treatment for TC patients, especially those who undergo histologic transformation.Keywords: thymic carcinoma, squamous cell carcinoma, small cell carcinoma, histologic transformation, anlotinib

Tongxin Liu,1– 4,* Quanquan Sun,1– 3,* Weifeng Qin,1– 4 Xiaozhong Chen,1– 4 Qiaoying Hu1– 4 1Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, People’s Republic of China; 2Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, People’s Republic of China; 3Key Laboratory of Radiation Oncology in Zhejiang Province, Hangzhou, Zhejiang 310022, People’s Republic of China; 4Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Hangzhou, Zhejiang 310022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiaoying HuDepartment of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang 310022, People’s Republic of ChinaEmail huqy316@hotmail.comPurpose: Esthesioneuroblastoma (ENB) is a type of rare malignant neoplasm of the sinonasal cavity. Optimal treatment for ENB is still controversial. A retrospective study was conducted to identify the clinical outcome and optimal treatment for ENB in the era of intensity-modulated radiation therapy (IMRT).Patients and Methods: Between December 2006 and August 2018, 37 patients with ENB without distant metastasis who underwent neoadjuvant chemotherapy followed by chemoradiotherapy (C+RC) or surgery followed by radiotherapy or chemoradiotherapy (S+R/RC) were retrospectively reviewed at our center.Results: The median follow-up period was 63.7 months (range, 13.2– 111.5 months). Five-year overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were similar between treatment arms (P values > 0.05). With a multivariate analysis, a Karnofsky Performance Status (KPS) of ≤ 80 was a prognostic factor for poor five-year OS. A KPS of ≤ 80 and Kadish class C–D tumors were prognostic factors for poor PFS. A KPS of ≤ 80 was a prognostic factor for poor LRFS. When KPS was ≤ 80 and tumors were Kadish class C–D, T3– 4 and N1 were prognostic factors for poor DMFS. Subgroup analyses also demonstrated that the two treatment arms exhibited similar trends for OS, PFS, LRFS, and DMFS, excluding patients with N1 or Kadish class A–B tumors (P values > 0.05).Conclusion: In the era of IMRT, S+R/RC failed to improve the outcomes of patients with ENB. C+RC may be a feasible treatment option for patients with ENB.Keywords: olfactory neuroblastoma, neoadjuvant chemotherapy, precise radiotherapy

Yicheng Li,1,2,* Wentao Xu,1,* Pu Chen,1,* Minjun Liao,1,3 Wanying Qin,1 Weijia Liao,1 Zhaoquan Huang1,4 1Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, People’s Republic of China; 2Second Clinical Medical College, Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China; 3Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China; 4Department of Pathology, Guilin Medical University, Guilin 541001, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weijia LiaoLaboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi, People’s Republic of ChinaEmail liaoweijia288@163.comZhaoquan HuangDepartment of Pathology, Guilin Medical University, Guilin 541001, Guangxi, People’s Republic of ChinaEmail 191990449@qq.comBackground: The purpose of this retrospective study was to investigate the relationship between serum iron levels and the prognosis and risk of recurrence in patients with hepatocellular carcinoma (HCC).Methods: A total of 253 HCC patients who underwent radical resection were involved in this study.Results: According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for preoperative serum iron in the assessment of HCC postoperative prognosis was 94 ug/dL. The overall survival (OS) of patients in the high iron group was significantly better than that in the low iron group (p < 0.001). The recurrence rate of patients in the low iron group was higher than that in the high iron group (p = 0.011). Correlation analysis showed that preoperative serum iron level was correlated with tumor size >5 cm (χ2 = 11.590, p < 0.001), recurrence (χ2 = 5.714, p = 0.017) and microvascular invasion (χ2 = 5.087, p = 0.024). In addition, univariate analysis showed that OS and disease-free survival (DFS) of HCC patients with high iron level were better than those with low iron level. Furthermore, multivariate COX proportional hazards regression analysis showed that serum iron ≤94 μg/dL, tumor size >5 cm, and microvascular invasion were independent predictors for shorter OS and DFS in HCC patients after operation, while recurrence was for shorter OS.Conclusion: Patients with low preoperative serum iron level had worse postoperative survival and higher recurrence rate in HCC. Preoperative serum iron is an independent predictor of HCC patients. For HCC patients with low iron levels, prognosis of patients may be improved if appropriate iron is supplemented.Keywords: HCC, serum iron, prognosis, recurrence, survival rate

Danyang Zhao,1,* Wenban Qin,2,* Chuanxiang Zhao,3 Jianxiong Long,4 Mujun Li1 1Department of Reproductive Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2Department of Oncology, Chongzuo People’s Hospital, Nanning 530021, Guangxi Province, People’s Republic of China; 3Department of General Surgery, The Second People’s Hospital of Shenzhen, Nanning 530021, Guangxi Province, People’s Republic of China; 4School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianxiong LongSchool of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530021, Guangxi Province, People’s Republic of ChinaEmail longjx12345@163.comMujun LiDepartment of Reproductive Center, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi 530021, People’s Republic of ChinaEmail sciencecid@126.comPurpose: Recent studies indicate that CXC chemokine receptor type 7 (CXCR7) is associated with tumorigenesis, progression, and metastasis of various cancers, but its roles and molecular mechanisms of action in cervical squamous cell carcinoma (CSCC) remain unclear. Our purpose was to explore the expression patterns of CXCR7 and epidermal growth factor receptor (EGFR) in CSCC and to identify possible correlations with clinical characteristics. We also tested whether CXCR7 can be a screening index for treatment options for CSCC stages IB1 and IIA1.Methods: Expression of CXCR7 and EGFR in tumors from 165 patients with CSCC was evaluated by immunohistochemistry and compared with the clinical data including survival.Results: Patients at CSCC stages IB1 and IIA1 received different treatment options, including radical hysterectomy, pelvic lymph node dissection, and para-aortic lymph node sampling (RH group, 67 patients) or pelvic external-beam radiation therapy with brachytherapy (EBRT group, 34 patients). Disease-free survival (DFS) and overall survival (OS) were compared between two groups at different CXCR7 expression levels. Immunohistochemical staining showed that CXCR7, EGFR, phospho-ERK, and phospho-AKT amounts increased from normal cervical epithelia and cervical intraepithelial neoplasia to CSCC, and CXCR7 was associated with the disease stage, lymph node metastasis, tumor size ≥40 mm, and EGFR expression. Kaplan–Meier analysis revealed that CXCR7 and EGFR expression was associated with shorter DFS and OS. Multivariate analysis suggested that CXCR7 was independently associated with DFS and OS. Prevalence of recurrence and distant metastasis was significantly lower in the EBRT group than in the RH group during CXCR7 expression. Besides, CXCR7 knockdown significantly decreased the proliferation and invasion of CSCC cells.Conclusion: CXCR7 is coexpressed with EGFR, which may be involved in ERK or AKT pathway activation. CXCR7 may be a screening index for treatment options at CSCC stages IB1 and IIA1.Keywords: CXC chemokine receptor type 7, cervical cancer, cancer treatment protocol

Shanshan Ma,* Tingting Zhang,* Li Jiang,* Wen Qin, Keyu Lu, Yong Zhang, Rensheng WangDepartment of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China*These authors contributed equally to this workObjective: This study aimed to investigate the impact of bladder volume on treatment planning and clinical outcomes of radiotherapy for patients with cervical cancer.Materials and methods: One hundred and sixty-six patients with locally advanced cervical cancer were selected in this retrospective study. The patients were divided into four groups according to their average bladder volume during radiotherapy (external beam radiation therapy and intracavitary brachytherapy): group A: V200 mL. The bladder volume and the cumulative dose to planning target (D90), bladder (D2cc), rectum (D2cc), and sigmoid (D2cc) were calculated using the treatment planning system. Treatment outcomes including late adverse events (the maximum grade of radiation-induced proctitis and cystitis), the objective response rate of tumor and lymph node, overall survival (OS), and progression-free survival (PFS) were collected. Additionally, the correlation between bladder volume and the irradiated dose of organs at risk and treatment outcomes was analyzed.Results: The median follow-up time was 28 months. The D90 and D2cc of the rectum in group A were the highest (P

Xiaoyun Hu,1 Wenyan Qin,1 Shanqiong Li,1 Miao He,1 Yilin Wang,1 Shu Guan,2 Haishan Zhao,1 Weifan Yao,1 Minjie Wei,1 Mingyan Liu,1 Huizhe Wu1 1Department of Pharmacology, School of Pharmacy, Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation, China Medical University, Shenyang 110122, China; 2Department of Breast Surgery, First Hospital of China Medical University, Shenyang 110001, China Objective: Multiple factors are involved in oxaliplatin-resistant process in colorectal cancer (CRC) patients including decreased drug accumulation and enhanced capacity to repair and tolerate DNA damage. In the present study, we aimed to assess the impact of six single-nucleotide polymorphisms (SNPs) in DNA repair genes and ABCG2 gene on prognosis in advanced CRC patients treated with oxaliplatin-based chemotherapy. Methods: In this study, 580 advanced CRC patients were recruited. Six SNPs of DNA repair genes (XPA rs10817938, XPA rs2808668, XPC rs2607775, and WRN rs1346044) and ABCG2 gene (rs2231142 and rs2622621) were genotyped by using the TaqMan assay. Results: Regarding interaction with environmental factors, ABCG2 rs2231142 and the first-degree family history of cancer and XPC rs2607775 or ABCG2 rs2622621 and lymph node metastases status demonstrated significant interactions. Of these six SNPs, XPA rs10817938 CT/TT genotypes retained its significant association with longer overall survival (OS) (P=0.008) in CRC patients receiving oxaliplatin-based chemotherapy (n=580). Furthermore, a significantly better impact on the disease-free survival (DFS) (P=0.001) and OS (P

Tongxin Liu,1–3,* Quanquan Sun,1,2,* Jing Chen,1–3 Fangzheng Wang,1–3 Bin Li,1–3 Weifeng Qin,1–3 Zhimin Ye,1–3 Fujun Hu1–3 1Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China; 2Key Laboratory of Radiation Oncology in Zhejiang Province, Hangzhou, China; 3Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Hangzhou, China *These authors contributed equally to this work Purpose: To compare the efficacy and safety of neoadjuvant chemotherapy (NACT) with gemcitabine (GEM) vs docetaxel plus cisplatin (CDDP) in locoregionally advanced nasopharyngeal carcinoma (NPC).Methods: A total of 222 patients with locoregionally advanced NPC between February 2012 and May 2014 in our hospital who received NACT with GEM or docetaxel plus CDDP combined with concurrent chemoradiotherapy (CCRT) were retrospectively analyzed. Fifty-two patients treated with GEM plus CDDP (GP) combined with CCRT were matched with 52 patients who received docetaxel plus CDDP (TP) combined with CCRT.Results: With a median follow-up time of 60 months (range, 14–72 months), the 5-year overall survival, progression-free survival (PFS), local relapse-free survival and distant metastasis-free survival (DMFS) rates were 78.8%, 66.0%, 81.0% and 75.9%, respectively, in the GP group and 79.4%, 60.5%, 79.6% and 73.6%, respectively, in the TP group. No statistically significant survival differences were found between the two groups. In multivariate analysis, T3–4 and N2–3 were prognostic factors for poor 5-year PFS and DMFS (all P-values 0.05).Conclusion: NACT with GP or TP regimen achieved comparable clinical outcome with acceptable toxicities. Both regimens might be a treatment option for patients with locoregionally advanced NPC. Keywords: nasopharyngeal carcinoma, IMRT, neoadjuvant chemotherapy, concurrent chemoradiotherapy

Tingdong Yu, Xiangkun Wang, Guangzhi Zhu, Chuangye Han, Hao Su, Xiwen Liao, Chengkun Yang, Wei Qin, Ketuan Huang, Tao Peng Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China Objective: The activities of four cytochrome P3A (CYP3A) subfamily members (CYP3A4, CYP3A5, CYP3A7, and CYP3A43) are well documented in drug metabolism. However, the association between CYP3A subfamily members and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic value of CYP3A subfamily mRNA expression levels with HCC prognosis. Materials and methods: Data from a total of 360 HCC patients were retrieved from The Cancer Genome Atlas database, and data from 231 HCC patients were retrieved from the Gene Expression Omnibus database. Kaplan–Meier analysis and Cox regression models were utilized to determine median survival, overall survival, and recurrence-free survival. Hazard ratios and 95% CI were calculated. Results: Low expression of CYP3A4, CYP3A5, and CYP3A43 in the tumor tissue was associated with short median survival (crude p=0.004, 0.001, and 0.001; adjusted p=0.022, 0.005, and 0.013, respectively). Joint-effects combination analysis of CYP3A4, CYP3A5/CYP3A4, CYP3A43/CYP3A5, and CYP3A43 revealed that high expression groups of two genes (group C, group c, group 3) were associated with a reduced risk of death, as compared to low expression of two genes (group A, group a, group 1), and the adjusted p values were 0.001, 0.004, and 0.001, respectively. Joint-effects analysis of CYP3A4, CYP3A5, and CYP3A43 showed that groups III and IV had a reduced risk of death, as compared to group I (adjusted p=0.024 and 0.002, respectively). Conclusion: CYP3A4, CYP3A5, and CYP3A43 mRNA expression levels are potential prognostic markers of HCC. Keywords: mRNA expression, CYP3A subfamily, hepatocellular carcinoma, prognosis, biomarker

Xiwen Liao,1,* Long Yu,1,* Xiaoguang Liu,1,2 Chuangye Han,1 Tingdong Yu,1 Wei Qin,1 Chengkun Yang,1 Guangzhi Zhu,1 Hao Su,1 Tao Peng1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China *These authors contributed equally to this work Background: The aim of this investigation was to identify candidate single nucleotide polymorphisms (SNPs) and molecular pathways associated with tumor protein p53 (TP53) expression status in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), clarify their potential mechanisms, and generate SNP-to-gene to pathway hypothesis. Materials and methods: Identify candidate Causal SNPs and Pathways (ICSNPathway) was used to perform pathway analysis based on the results of our previous genome-wide association study of TP53 expression status in 387 HBV-related HCC patients. Results: Through the ICSNPathway analysis, we identified 18 candidate SNPs and 10 candidate pathways that are associated with TP53 expression status in HBV-related HCC. The strongest mechanism involved the modulation of major histocompatibility complex, class II, DP beta 1 (human leukocyte antigen [HLA]-DPB1-rs1042153), major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1-rs1130399, HLA-DQB1-rs1049056, HLA-DQB1-rs1049059, and HLA-DQB1-rs1049060), and major histocompatibility complex, class II, DR beta 1 (HLA-DRB1-rs35445101). SNPs consequently affected regulatory roles in all the candidate pathways except hematopoietic cell lineage pathways. Association analysis using the GSE14520 data set, Gene Multiple Association Network Integration Algorithm, and Search Tool for the Retrieval of Interacting Genes/Proteins suggests that all genes of the candidate SNPs were associated with TP53. Survival analysis showed that the collagen type VI alpha 3 chain (COL6A3) rs111231885 and COL6A3-rs113155945 and COL6A3 block 4 CC haplotypes with TP53 negative status may have protective effects in HBV-related HCC patients after hepatectomy. Conclusion: Our pathway analysis identified 18 candidate SNPs and 10 candidate pathways that were associated with TP53 expression status in HBV-related HCC. Among these candidate SNPs, the genetic variation of COL6A3 may be a potential prognostic biomarker of HBV-related HCC. Keywords: TP53, hepatocellular carcinoma, hepatitis B virus, genome-wide association study, pathway analysis

Xinping Ye,* Xiangkun Wang,* Liming Shang, Guangzhi Zhu, Hao Su, Chuangye Han, Wei Qin, Guanghui Li, Tao Peng Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Province, China *These authors contributed equally to this work Objective: Acetaldehyde dehydrogenase 2 (ALDH2) and cytochrome P450 2E1 (CYP2E1) have been associated with hepatocellular carcinoma (HCC) susceptibility and prognosis. The polymorphisms ALDH2 rs671 and CYP2E1 rs2031920 are reportedly correlated with the prevalence of HCC in other countries. The aim of this study was to investigate associations between ALDH2 and CYP2E1, and HCC susceptibility in a population of Guangxi, southern China, an area with a high incidence of HCC.Patients and methods: The study cohort included 300 HCC cases, 292 healthy controls for HCC susceptibility analysis, and another 20 HCC cases and 10 healthy controls for ascertainment. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method.Results: The study results demonstrated that mutant genotypes of ALDH2 (G/A and A/A) led to significant differences in HCC susceptibility, as compared with the wild genotype (G/G) with the same C1/C1 genotype in non-drinking individuals (adjusted P=0.010, OR=0.20, 95% CI=0.06–0.68). The mutant genotypes of CYP2E1 (C1/C2 and C2/C2) brought about significant differences in HCC susceptibility, as compared with the wild genotype (C1/C1) and the same G/G genotype (adjusted P=0.025, OR=0.42, 95% CI=0.20–0.90). Drinking plays a role in HCC susceptibility in the same G/G genotype individuals (adjusted P=0.004, OR=0.32, 95% CI=0.15–0.69), but had no impact when combined with CYP2E1 for analysis (all P>0.05).Conclusion: These results suggest that the mutant genotypes of ALDH2 and CYP2E1 may be protective factors for HCC susceptibility in Guangxi province, China. Keywords: hepatocellular carcinoma susceptibility, genetic polymorphism, ALDH2, CYP2E1, Chinese population

Xiaoguang Liu,* Chuangye Han,* Xiwen Liao, Long Yu, Guangzhi Zhu, Hao Su, Wei Qin, Sicong Lu, Xinping Ye, Tao Peng Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China *These authors contributed equally to this work Background: The upregulated expression of versican (VCAN) promotes the proliferation, invasion, and metastasis of various types of human cancer cells, including hepatocellular carcinoma (HCC) cells. Patients and methods: In this study, genetic variants in the exon region of VCAN were genotyped by DNA sequencing. Prognostic values of VCAN exon single nucleotide polymorphisms (SNPs) were assessed by Kaplan–Meier with the log-rank test, and uni- and multivariate Cox proportional hazard regression model. Results: A total of 111 patients with resected hepatitis B virus-associated early-stage HCC were collected for genotyping VCAN exon SNPs using Sanger DNA sequencing. Haplotype analysis was performed using Haploview 4.2. Survival data were analyzed using Kaplan–Meier curves and Cox proportional hazards regression analyses. The rs2652098, rs309559, rs188703, rs160278, and rs160277 SNPs were significantly associated with overall patient survival (p