• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7097-7103
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• 2014

Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Our data suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6293-6299
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• 2013

Background: A number of clinicopathologic factors have been found to be associated with pathological lymph node metastasis (pLNM) in rectal cancer; however, most of them can only be identified by expensive high resolution imaging or obtained after surgical treatment. Just like the Child-Turcotte-Pugh (CTP) and the model for end-stage liver disease (MELD) scores which have been widely used in clinical practice, our study was designed to assess the pre-operative factors which could be obtained easily to predict intra-operative pLNM in rectal cancer. Methods: A cohort of 469 patients who were treated at our hospital in the period from January 2003 to June 2011, and with a pathologically hospital discharge diagnosis of rectal cancer, were included. Clinical, laboratory and pathologic parameters were analyzed. A multivariate unconditional logistic regression model, areas under the curve (AUC), the Kaplan-Meier method (log-rank test) and the Cox regression model were used. Results: Of the 469 patients, 231 were diagnosed with pLNM (49.3%). Four variables were associated with pLNM by multivariate logistic analysis, age<60 yr (OR=1.819; 95% CI, 1.231-2.687; P=0.003), presence of abdominal pain or discomfort (OR=1.637; 95% CI, 1.052-2.547; P=0.029), absence of allergic history (OR=1.879; 95% CI, 1.041-3.392; P=0.036), and direct $bilirubin{\geq}2.60{\mu}mol/L$ (OR=1.540; 95% CI, 1.054-2.250; P=0.026). The combination of all 4 variables had the highest sensitivity (98.7%) for diagnostic performance. In addition, age<60 yr and direct $bilirubin{\geq}2.60{\mu}mol/L$ were found to be associated with prognosis. Conclusion: Age, abdominal pain or discomfort, allergic history and direct bilirubin were associated with pLNM, which may be helpful for preoperative selection.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6111-6116
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• 2015

Background: Stomach cancer is one of leading causes of death worldwide. In Thailand, the incidence and mortality of stomach cancer are in the top ten for cancers. Effects of DNA repair gene X-ray repair cross complementary protein 1 (XRCC1) polymorphisms and clinicopathological characteristics on survival of stomach cancer in Thailand have not been previously reported. The aim of this study was to investigate the effects of XRCC1 gene and clinicopathological characteristics on survival of stomach cancer patients in Thailand. Materials and Methods: Data and blood samples were collected from 101 newly diagnosed stomach cancer cases pathologically confirmed and recruited during 2002 to 2006 and followed-up for vital status until 31 October 2012. Genotype analysis was performed using real-time PCR-HRM. The data were analyzed using the Kaplan-Meier method to yield cumulative survival curve, log-rank test to assess statistical difference of survival and Cox proportional hazard models to estimate adjusted hazard ratio. Results: The total followed-up times were 2,070 person-months, and the mortality rate was 4.3 per 100 person-months. The median survival time after diagnosis was 8.07 months. The cumulative 1-, 3-, 5-years survival rates were 40.4%, 15.2 % and 10.1 % respectively. After adjustment, tumour stage were associated with an increased risk of death (p= 0.036). The XRCC1 Gln339Arg, Arg/Arg homozygote was also associated with increased risk but statistically this was non-significant. Conclusions: In addition to tumour stage, which is an important prognostic factor affecting to the survival of stomach cancer patients, the genetic variant Gln339Arg in XRCC1 may non-significantly contribute to risk of stomach cancer death among Thai people. Larger studies with different populations are need to verify ours findings.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8893-8900
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• 2014

Dysregulated expression of microRNAs (miRNAs) has been shown to be closely associated with tumor development, progression, and carcinogenesis. However, their clinical implications for gastric cancer remain elusive. To investigate the hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were employed to examine miRNA expression profiles for the 5-pair discovery stage, and the quantitative real-time polymerase chain reaction (qRTPCR) was applied to validate candidate miRNAs for 48-pair validation stage. Furthermore, the relationship between altered miRNA and clinicopathological features and prognosis of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be significantly different expressed in tissues from gastric cancer compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was significantly associated with poor differentiation (p=0.022). Moreover, binary logistic regression analysis demonstrated that the UICC stage was a significant risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91; p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with a high fold-change of down-regulated miR-193b had a significantly shorter survival time (n=19; median survival=29 months) compared to patients with a low fold-change of down-regulated miR-193b (n=29; median survival=54 months) (p=0.001). Overall survival time of patients with a low fold-change of up-regulated miR-196a (n=27; median survival=52 months) was significantly longer than that of patients with a high fold-change of up-regulated miR-196a (n=21; median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied as novel and promising prognostic markers in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2979-2986
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• 2014

Background: Recently, peroxiredoxin3 (PRDX3) was identified as a novel molecular marker for the progression of hepatocellular carcinoma (HCC). However, its potential clinical application as a serum marker for the early diagnosis and prognosis of HCC has not been investigated. Methods: PRDX3, alpha-fetaprotein (AFP), and other biochemical parameters were measured in serum samples from 297 Chinese patients, including 96 with HCC, 98 with liver cirrhosis (LC), and 103 healthy controls (HCs). Correlations between serum PRDX3 expression and clinicopathological variables and the relationship between serum PRDX3 expression and prognosis were analyzed. Results: Serum PRDX3 was significantly higher in HCC patients than in the LC and HC groups. The sensitivity and specificity of serum PRDX3 for the diagnosis of HCC were 85.9% and 75.3%, respectively, at a cutoff of 153.26 ng/mL, and the area under the curve was 0.865. Moreover, serum PRDX3 expression was strongly associated with AFP level, tumor diameter, TNM stage, and portal vein invasion. Kaplan-Meier curve analysis revealed that HCC patients with high serum PRDX3 expression had a shorter median survival time than those with low PRDX3 expression. Moreover, serum PRDX3 expression was an independent risk factor for overall survival. The inverse correlation between serum PRDX3 and patient survival remained significant in patients with early-stage HCC and in those with normal serum AFP levels. Conclusions: Serum PRDX3 can be used as a noninvasive biomarker for the diagnosis and/or prognosis of HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6165-6171
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• 2013

This study aimed to analyze the expression and clinical significance of cyclin G2 (CCNG2) in thyroid carcinoma and the biological effects of CCNG2 overexpression in a cell line. Immunohistochemistry and Western blotting were used to analyze CCNG2 protein expression in 63 cases of thyroid cancer and normal tissues to allow the relationship with clinical factors to be assessed. CCNG2 lentiviral and empty vectors were transfected into the thyroid cancer K1 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were applied to detect the mRNA and protein levels of CCNG2. MTT assay and cell cycle were also conducted to assess the influence of up-regulated expression of CCNG2 on K1 cell biology. The level of CCNG2 protein expression was found to be significantly lower in thyroid cancer tissue than normal tissues (P<0.05). Western blot: The relative amount of CCNG2 protein in thyroid cancer tissue was respectively found to be significantly lower than in normal tissues (P<0.05), correlating with lymph node metastasis, clinic stage and histological grade (P<0.05), but not gender, age or tumor size (P>0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time on Kaplan-Meier analysis (P<0.05). The results for biological functions showed that K1 cell transfected CCNG2 had a lower survival fraction, a greater percentage in the G0/G1 phases, and lower cyclin-dependent kinase 2 (CDK2) protein expression compared with K1 cells non-transfected with CCNG2 (P<0.05). CCNG2 expression decreased in thyroid cancer and correlated significantly lymph node metastasis, clinic stage, histological grade and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator in thyroid cancer K1 cells by promoting degradation of CDK2.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4567-4570
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• 2013

Background: Nasopharyngeal carcinoma (NPC) is the commonest radiocurable cancer in Malaysia. This study aimed to determine the treatment outcomes and late effects of radiotherapy for NPC patients treated in University Malaya Medical Centre (UMMC). Materials and Methods: All newly diagnosed patients with NPC referred for treatment to the Oncology unit at UMMC from 2004-2008 were retrospectively analyzed. Treatment outcomes were 5 years overall survival (OS), disease free survival (DFS), cause-specific survival (CSS), locoregional control (LRC) and radiotherapy-related late effects. The Kaplan-Meier method was used for survival analysis and differences in survival according to AJCC stage was compared using the log-rank test. Results: A total of 176 patients with newly diagnosed NPC were treated in UMMC during this period. Late presentation was common, with 33.5% presenting with T3-4 disease, 84.7% with N1-3 disease and 75.6% with AJCC stage 3-4 disease. Radical RT was given to 162 patients with 22.7% having RT alone and 69.3% having CCRT. The stipulated OTT was 7 weeks and 72.2% managed to complete their RT within this time period. Neoadjuvant chemotherapy was given to 14.8% while adjuvant chemotherapy was administered to 16.5%. The 5 years OS was 51.6% with a median follow up of 58 months. The 5 years OS according to stage were 81.8% for stage I, 77.9% for stage II, 47.4% for stage III and 25.9% for stage IV. The 5 years overall CSS, DFS and LRC were 54.4%, 48.4% and 70.6%, respectively. RT related late effects were documented in 80.2%. The commonest was xerostomia (66.7%). Other documented late effects were hearing deficit (17.3%), visual deficit (3.1%), neck stiffness (3.1%), dysphagia (3.4%), cranial nerve palsy (2.5%), pneumonitis (0.6%) and hypothyroidism (1.2%). Conclusions: The 5 years OS and LRC in this study are low compared to the latest studies especially those utilizing IMRT. Implementation of IMRT for NPC treatment should be strongly encouraged.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1759-1767
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• 2016

Background: Uterine sarcoma is a group of rare gynecologic tumors with various natures, and different lines of treatment. Most have a poor treatment outcome. This study targeted clinical characteristics, treatment, overall survival (OS), progression-free survival (PFS), and prognostic factors in uterine sarcoma patients in one tertiary center for cancer care. Materials and Methods: Uterine sarcoma patients who were treated at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital between January 1994 and December 2014 were identified. Clinico-pathological data were analyzed. Prognostic outcomes were examined by Kaplan-Meier curves and Cox regression analysis. Results: We identified 46 uterine sarcoma patients: 25 carcinosarcoma (CS) (54.3%), 15 leiomyosarcoma (LMS) (32.6%), and 6 undifferentiated uterine sarcoma (UUS) (13.1%) cases. Mean age was $54.0{\pm}11.9years$ (range 25-82 years). Abnormal uterine bleeding was the most common presenting symptom (63.0%). Among 33 patients (71.7%) who had pre-operative tissue collected, diagnosis of malignancy was correct in 29 (87.9%). All patients received primary surgery and retroperitoneal lymph nodes were resected in 34 (73.9%). After surgery, 5 (10.9%) had gross residual tumors. Stage I disease was most commonly found (56.5%). Adjuvant treatment was given to 27 (58.7%), most commonly chemotherapy. After a median follow-up of 16.0 months (range 0.8-187.4 months), recurrence was encountered in 22 patients (47.8%). Median time to recurrence was 5.8 months (range1.0-105.5 months). Distant metastasis was more common than local or locoregional failure. The 2-year PFS was 45.2% (95% confidence interval [CI], 30.6%-59.7%) and the 2-year OS was 48.3% (95% CI, 33.3%-60.7%). Multivariable analyses found residual disease after surgery as a significant factor only for PFS. Conclusions: Uterine sarcoma is a rare tumor entity. Even with multimodalities of treatment, the prognosis is still poor. Successful cytoreductive surgery is a key factor for a good survival outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3267-3272
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• 2015

Purpose: To retrospective assess the potential predictors for relapse and create an effective clinical mode for surveillance after orchidectomy in clinical stage I non-seminomatous germ cell testicular tumors (CSI-NSGCTs). Materials and Methods: We analyzed data for CSI-NSGCTs patients with non-lymphatic vascular invasion, %ECa < 50% (percentage of embryonal carcinoma < 50%), and negative or declining tumor markers to their half-life following orchidectomy (defined as low-risk patients); these patients were recruited from four Chinese centers between January 1999 and October 2013. Patients were divided into active surveillance group and retroperitoneal lymph node dissection (RPLND) group according to different therapeutic methods after radical orchidectomy was performed. The disease-free survival rates (DFSR) and overall survival rates (OSR) of the two groups were compared by Kaplan-Meier analysis. Results: A total of 121 patients with CSI-NSGCT were collected from four centers, and 81 low-risk patients, including 54 with active surveillance and 27 with RPLND, were enrolled at last. The median follow-up duration was 66.2 (range 6-164) months in the RPLND group and 65.9 (range 8-179) months in the surveillance group. OSR was 100% in active surveillance and RPLND groups, and DFSR was 89.8% and 87.0%, respectively. No significant difference was observed between these two groups ($X_2=0.108$, P=0.743). No significant difference was observed between the patients with a low percentage of embryonal carcinoma (<50%) and those without embryonal carcinoma (87.0% and 91.9%, $X_2=0.154$, P=0.645). No treatment-related complications were observed in the active surveillance group whereas minor and major complications were observed in 13.0% and 26.1% of the RPLND group, respectively. Conclusions: Active surveillance resulted in similar DFSR and OSR compared with RPLND in our trial. Patients with low-risk CSI-NSGCTs could benefit from risk-adapted surveillance after these patients were subjected to radical orchidectomy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2101-2107
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• 2012

Treatment responses of $N_0$ stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with $N_0$ NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with $N_0$ NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with $N_0$ NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.