• Nutrition Research and Practice
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• v.14 no.1
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• pp.20-24
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• 2020

BACKGROUND/OBJECTIVES: Malnutrition has multiple impacts on surgical success, postoperative complications, duration of hospital stay, and costs, particularly for cancer patients. There are various nutrition risk screening tools available for clinical use. Herein, we aim to determine the most appropriate nutritional risk screening system for esophageal cancer (EC) patients in China. SUBJECTS/METHODS: In total, 138 EC patients were enrolled in this study and evaluated by experienced nurses using three different nutritional screening tools, the Nutrition Risk Screening 2002 tool (NRS2002), the Patient-generated Subjective Globe Assessment (PG-SGA), and the Nutrition Risk Index (NRI).We compared sensitivity, specificity, positive and negative likelihood ratios, and Youden index generated by each of the three screening tools. Finally, cut-off points for all three tools were re-defined to optimize and validate the best nutritional risk screening tool for assessing EC patients. RESULTS: Our data suggested that all three screening tools were 100% sensitive for EC patients, while the specificities were 44.4%, 2.96%, and 59.26% for NRS 2002, PG-SGA, and NRI, respectively. NRI had a higher positive likelihood ratio as well as a higher area under the receiver operating characteristic curve compared to those of NRS 2002 and PG-SGA; although, all three tools had null negative likelihood ratios. After adjusting the cut-off points, the specificity and accuracy for all tools were significantly improved, however, the NRI remained the most appropriate nutritional risk screening system for EC patients. CONCLUSIONS: The NRI is the most suitable (highest sensitivity and accuracy) nutritional risk screening tool for EC patients. The performance of the NRI can be significantly improved if the cut-off point is modified according to the results obtained using MedCalc software.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5437-5442
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• 2014

Esophageal squamous cell carcinoma (ESCC) is one of the most malignancies with a poor prognosis. The phospholipase $C{\varepsilon}$ gene (PLCE1) encodes a novel ras-related protein effector mediating the effects of R-Ras on the actin cytoskeleton and membrane protrusion. However, molecular mechanisms pertinent to ESCC are unclear. We therefore designed PLCE1-special small interfering RNA and transfected to esophageal squamous cell (EC) 9706 cells to investigat the effects of PLCE1 gene silencing on the cell cycle and apoptosis of ESCC and indicate its important role in the development of ESCC. Esophageal cancer tissue specimens and normal esophageal mucosa were obtained and assayed by immunohistochemical staining to confirm overexpression of PLCE1 in neoplasias. Fluorescence microscopy was used to examine transfection efficiency, while the result of PLCE1 silencing was examined by reverse transcription (RT-PCR). Flow cytometry and annexin V apoptosis assays were used to assess the cell cycle and apoptosis, respectively. Expression of cyclin D1 and caspase-3 was detected by Western-blotting. The level of PLCE1 protein in esophageal cancer tissue was significantly higher than that in normal tissue. After transfection, the expression of PLCE1 mRNA in EC 9706 was significantly reduced, compared with the control group. Furthermore, flow cytometry results suggested that the PLCE1 gene silencing arrested the cell cycle in the G0/G1 phase; apoptosis was significantly higher than in the negative control group and mock group. PLCE1 gene silencing by RNAi resulted in decreased expression of cyclin D1 and increased expression of caspase-3. Our study suggests that PLCE1 may be an oncogene and play an important role in esophageal carcinogenesis through regulating proteins which control cell cycling and apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.691-694
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• 2014

Background: Tumor length in patients with esophageal cancer (EC) has recently received great attention. However, its prognostic role for EC is controversial. The purpose of our study was to characterize the prognostic value of tumor length in EC patients and offer the optimum cut-off point of tumor length by reliable statistical methods. Materials and Methods: A retrospective analysis was conducted on 71 consecutive patients with EC who underwent surgery. ROC curve analysis was used to determine the optimal cut-off point for tumor length, measured with a handheld ruler after formalin fixation. Correlations between tumor length and other factors were surveyed, and overall survival (OS) rates were compared between the two groups. Potential prognostic factors were evaluated by univariate Kaplan-Meier survival analysis. A P value less than 0.05 was considered significant. Results: There were a total of 71 patients, with a male/female divide of 43/28 and a median age of 59. Characteristics were as follows: squamous/adenocarcinoma, 65/6; median tumor length, 4 (0.9-10); cut-off point for tumor length, 4cm. Univariate analysis prognostic factors were tumor length and modality of therapy. One, three and five year OS rates were 84, 43 and 43% for tumors with ${\leq}4cm$ length, whereas the rates were 75, 9 and 0% for tumors >4 cm. There was a significant association between tumor length and age, sex, weight loss, tumor site, histology, T and N scores, differentiation, stage, modality of therapy and longitudinal margin involvement. Conclusions: Future studies for modification of the EC staging system might consider tumor length too as it is an important prognostic factor. Further assessment with larger prospective datasets and practical methods (such as endoscopy) is needed to establish an optimal cut-off point for tumor length.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3183-3186
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• 2013

Purpose: The 7th edition of the American Joint Committee on Cancer Staging Manual for esophageal cancer (EC) categorizes N stage according to the number of metastatic lymph nodes (LNs), irrespective of the site. The aim of this study was to determine the prognostic value of subcarinal LN metastasis in patients undergoing esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: A retrospective analysis of 507 consecutive patients with ESCC was conducted. Potential clinicopathological factors that could influence subcarinal LN metastasis were statistically analyzed. Univariate and multivariate analyses were also performed to evaluate the prognostic parameters for survival. Results: The frequency of subcarinal LN metastasis was 22.9% (116/507). Logistic regression analysis showed that tumor length (>3cm vs ${\leq}3cm$; P=0.027), tumor location (lower vs upper/middle; P=0.009), vessel involvement (Yes vs No; P=0.001) and depth of invasion (T3-4a vs T1-2; P=0.012) were associated with 2.085-, 1.810-, 2.535- and 2.201- fold increases, respectively, for risk of subcarinal LN metastasis. Multivariate analyses showed that differentiation (poor vs well/moderate; P=0.001), subcarinal LN metastasis (yes vs no; P=0.033), depth of invasion (T3-4a vs T1-2; P=0.014) and N staging (N1-3 vs N0; P=0.001) were independent prognostic factors. In addition, patients with subcarinal LN metastasis had a significantly lower 5-year cumulative survival rate than those without (26.7% vs 60.9%; P<0.001). Conclusions: Subcarinal LN metastasis is a predictive factor for long-term survival in patients with ESCC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8413-8422
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• 2014

Background: To investigate the relationship of five TP53 polymorphisms (p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a) with the esophageal cancer (EC) risk in North Indians. Materials and Methods: Genotyping of p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a polymorphisms of TP53 in 136 sporadic EC patients and 136 controls using polymerase chain reaction and PCR-RFLP. Results: The frequencies of genotype RR, RP and PP of p.R72P polymorphism were 16.91 vs 26.47%, 58.82 vs 49.27% and 24.27 vs 24.27% among patients and controls respectively. We observed significantly increased frequency of RP genotype in cases as compared to controls (OR=1.87, 95% CI, 1.01-3.46, p=0.05). The frequencies of genotype A1A1, A1A2 and A2A2 of PIN3 ins16bp polymorphism were 69.12 vs 70.59%, 27.20 vs 25% and 3.68 vs 4.41% among patients and controls. There was no significant difference among genotype and allele distribution between patients and controls. The frequencies of genotype GG, GA and AA of r.13494g>a polymorphism were 62.50 vs 64.70%, 34.56 vs 30.15% and 2.94 vs 5.15% among patients and controls respectively. No significant difference between genotype and allele frequency was observed in the patients and controls. For p.P47S and p.R213R polymorphisms, all the cases and controls had homozygous wild type genotype. The RP-A1A1-GG genotype combination shows significant risk for EC (OR=2.01, 95%CI: 1.01-3.99, p=0.05). Conclusions: Among the five TP53 polymorphisms investigated, only p.R72P polymorphism may contributes to EC susceptibility.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3613-3618
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• 2014

Stathmin, also called oncoprotein 18, is a founding member of the family of microtubule-destabilizing proteins that play a critical role in the regulation of mitosis. At the same time stathmin has been recognized as one of responsible factors in cancer cells. The aim of this study was to assess stathmin status, its correlations with clinicopathological parameters and its role as a progosnostic marker in EC patients. The protein and mRNA levels of stathmin were examined byimmunohistochemistry (IHC) and in situ hybridization in 100EC tissues and adjacent noncancerous tissues. mRNA and protein expression of stathmin in three EC cell lines(EC9706, ECa109, EC1 commonly used in research) were also analyzed using immunocytochemistry, western blot and in situ hybridization. The prognostic value of Stathmin expression within the tumor tissues were assessed by Cox regression and Kaplan-Meier analysis. We showed that stathmin expression was significantly higher in EC tissues than in adjacent noncancerous tissues. High stathmin immunostaining score in the EC was positively correlated with tumor differentiation, Tumor invasion, Lymph node metastases, and TNM stage. In addition, we demonstrated that three EC cell lines examined, were constitutively expressing a high level of stathmin. Of those, EC-1 showed the strongest mRNA and protein expression for the stathmin analyzed. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in EC patients with high Stathmin expression, compared to those with low expression of Stathmin expression. Furthermore, multivariate Cox proportional hazard analyses revealed that Stathmin was an independent factors affecting the overall survival probability. In conclusion, our data provide a basis for the concept that stathmin might be associated with EC development and progression. High levels of Stathmin expression in the tumor tissues may be a good prognostic marker for patients with EC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7375-7379
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• 2013

The main aim of this study was to investigate the roles of GST-${\pi}$ and $pol{\beta}$ genes in the chemoresistance of esophageal carcinoma cells. Eukaryotic expression vectors containing each gene were constructed and transfected into EC9706 cells, and the biological effects of the two genes assessed based on a resistance index. We additionally investigated the in vitro and in vivo anti-resistance effects of GST-${\pi}$ and $pol{\beta}$ genes using recombinant lentiviruses carrying siRNAs against the two genes. Our results showed that upregulation of GST-${\pi}$ and $pol{\beta}$ genes suppresses chemosensitivity of esophageal carcinoma cells to cisplatin, while downregulation of these two genes with RNAi technology reverses this chemoresistance. Multi-site injection of recombinant lentivirus targeting the GST-${\pi}$ gene into transplanted cDDP tumors effectively reversed their chemoresistant phenotype. However, the same treatment against the $pol{\beta}$ gene did not lead to significant efficacy against chemoresistance.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.1943-1948
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• 2014

Purpose: The prevalence of weight loss in esophageal carcinoma patients is high and associated with impairment of physical function, increased psychological distress and low quality of life. It is not known which factors may contribute to weight loss in patients with esophageal carcinoma during radiotherapy in China. The objective of this study was to identify the associated demographic and clinical factors influencing weight loss. Methods: We evaluated 159 esophageal carcinoma patients between August 2010 and August 2013 in a crosssectional, descriptive study. Patient characteristics, tumor and treatment details, psychological status, adverse effects, and dietary intake were evaluated at baseline and during radiotherapy. A multivariate logistic regression analyss was performed to identify the potential factors leading to weight loss. Results: 64 (40.3%) patients had weight loss ${\geq}5%$ during radiotherapy. According to logistic regression analysis, depression, esophagitis, and loss of appetite were adverse factors linked to weight loss. Dietary counseling, early stage disease and total energy intake ${\geq}1441.3$ (kcal/d) were protective factors. Conclusions It was found that dietary counseling, TNM stage, total energy intake, depression, esophagitis, and loss of appetite were the most important factors for weight loss. The results underline the importance of maintaining energy intake and providing dietary advice in EC patients during RT. At the same time, by identifying associated factors, medical staff can provide appropriate medical care to reduce weight loss. Further studies should determine the effect of these factors on weight loss and propose a predictive model.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.61-73
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• 2023

Esophageal squamous cell carcinoma (ESCC) is a kind of malignant tumor with high incidence and mortality in the digestive system. The aim of this study is to explore the function of lnc-ABCA12-3 in the development of ESCC and its unique mechanisms. RT-PCR was applied to detect gene transcription levels in tissues or cell lines like TE-1, EC9706, and HEEC cells. Western blot was conducted to identify protein expression levels of mitochondrial apoptosis and toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway. CCK-8 and EdU assays were carried out to measure cell proliferation, and cell apoptosis was examined by flow cytometry. ELISA was used for checking the changes in glycolysis-related indicators. Lnc-ABCA12-3 was highly expressed in ESCC tissues and cells, which preferred it to be a candidate target. The TE-1 and EC9706 cells proliferation and glycolysis were obviously inhibited with the downregulation of lnc-ABCA12-3, while apoptosis was promoted. TLR4 activator could largely reverse the apoptosis acceleration and relieved the proliferation and glycolysis suppression caused by lnc-ABCA12-3 downregulation. Moreover, the effect of lnc-ABCA12-3 on ESCC cells was actualized by activating the TLR4/NF-κB signaling pathway under the mediation of exosome. Taken together, the lnc-ABCA12-3 could promote the proliferation and glycolysis of ESCC, while repressing its apoptosis probably by regulating the TLR4/NF-κB signaling pathway under the mediation of exosome.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10267-10272
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• 2015

To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.