Abstract Colorectal cancer (CRC) is one of the most common malignant tumors and places an enormous burden on society. The US FDA approved the application of Epi proColon on 12 April 2016, and permitted the application of the Septin9 gene methylation assay as a CRC screening test for average-risk population over 50 years old. The effectiveness of methylated Septin9 for CRC detection has been reviewed in the newly published recommendation statement by US Preventive Services Task Force (USPSTF). The Septin9 gene methylation assay is more cost efficient with higher compliance than the stool DNA test, and has been proven to be an accurate, reliable, fast, and convenient molecular test. However, the currently FDA approved Epi proColon assay needs to perform triplicated PCR reactions for each sample which leads to high cost. In order to improve the sensitivity and specificity, simplify the operational procesure, and reduce cost, we have developed an new Septin9 gene methylation assay in which the specific sequences of both methylated DNA strands and control gene could be amplificated and detected in one reaction. We evaluated sensitivity, specificity, and clinical performance using plasma samples from colonoscopy negative individuals and CRC patients. The preliminary data showed that the sensitivity and specificity for CRC detection was 77.4%(41/53) ,97.8%(90/92) respectively. A large scale clinical study with more than 1000 subjects is currently in progress. In conclusion, we have developed a new Septin9 gene methylation assay detecting double DNA strands, which demonstrated improved performance for early detection of CRC in clinical setting. Citation Format: Qiuju Liang, Zhengbin Huang, Qingwen Xu, Feipeng Xu, Wenwei Huang, Wenfang Xie, Lei Zeng, Jiasu Liu, De-Hua Yu. A newly developed Septin9 gene methylation assay dectecting double DNA strands for screening of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3329.
Objective
To investigate the expression and its clinical significance of M2-pyruvate kinase (PKM2) and phosphatase and tensin homologue deleted on chromosome ten (PTEN) in gastric carcinoma.
Methods
The expression levels of PKM2 and PTEN in 88 cases of gastric carcinoma tissues and adjacent gastric tissues were detected by immunohistochemistry.
Results
The expression rate of PKM2 was 71.59% (63/88) in gastric carcinoma tissues, and 30.68% (27/88) in non-cancerous adjacent gastric tissues (t=29.470, P=0.000). The expression of PKM2 was correlated to TNM stage and lymph node metastasis of gastric carcinoma (respectively, t=4.130, P=0.040; t=5.840, P=0.020). The expression rate of PTEN was 39.77% (35/88) in gastric carcinoma tissues, and 92.05% (81/88) in non-cancerous adjacent gastric tissues (t=53.510, P=0.000). The expression of PTEN was correlated to TNM stage, histology grade and lymph node metastasis of gastric carcinoma (t=5.550, P=0.020; t=4.330, P=0.040; t=5.840, P=0.020, respectively).
Conclusion
The expression of PKM2 and PTEN may be correlated to the carcinogenesis and progression of gastric carcinoma.
Key words:
Gastric carcinoma; M2-pyruvate kinase; Phosphatase and tensin homologue deleted on chromosome ten; Immunohistochemical method
Objective
To explore the expression of Kruppel-like factor 4 (KLF4) and kinesin family member 20A(KIF20A) in gastric carcinoma and their clinical value.
Methods
Gastric carcinoma tissues and adjacent gastric tissues of 69 patients confirmed pathologically at Affiliated Hospital of Guangdong Medical University From May 2014 to February 2019 were collected. The expression of KLF4 and KIF20A proteins in gastric carcinoma tissues and adjacent gastric tissues was detected by immunohistochemistry.
Results
The positive expression rate of KLF4 in gastric carcinoma tissues was significantly lower than that of adjacent gastric tissues (43.48% vs. 78.26%, t=17.524, P<0.01). The positive expression of KLF4 was significantly related with the histology grade, TNM stage and lymph node metastasis of gastric carcinoma (respectively, t=4.261, 4.653, 6.104, P<0.05). The positive expression rate of KIF20A in gastric carcinoma tissues was significantly higher than that of non-cancerous adjacent gastric tissues (66.67% vs. 20.29%, t=30.195, P<0.01), and the positive expression of KIF20A was related with gastric carcinoma to TNM stage and lymph node metastasis (respectively, t=6.048, 4.246, P<0.05).
Conclusion
There was low expression of KLF4 and high expression of KIF20A in gastric carcinoma tissues. Both KLF4 and KIF20A may play important role in the occurrence and development of gastric carcinoma.
Key words:
Kruppel-like factor 4; Kinesin family member 20A; Immunohistochemical method; Gastric carcinoma
Objective
To investigate the expression of Silentmating information regulater 2 (SIRT2), ribosomal protein S15a (RPS15a) in gastric carcinoma and adjacent gastric tissues, and to explore their relationship with clinicopathological features of gastric carcinoma.
Methods
Gastric carcinoma tissues and adjacent gastric tissues of 75 patients pathologically confirmed From January 2015 to May 2019 were collected, The expression of SIRT2 and RPS15a proteins in gastric carcinoma tissues and adjacent gastric tissues were detected by using immunohistochemical method.
Results
The expression rate of SIRT2 was 70.67% (53/75) in gastric carcinoma tissues, and 18.67% (14/75) in non-cancerous adjacent gastric tissues (χ2=41.027, P<0.01), the positive expressions of SIRT2 were related with gastric carcinoma to tumor size, TNM stage and lymph node metastasis (Respectively, χ2=7.474, 8.495, 4.647, P<0.05); the expression rate of RPS15a was 80.00%(60/75) in gastric carcinoma tissues, and 42.67%(32/75) in non-cancerous adjacent gastric tissues (χ2=22.039, P<0.01), the positive expressions of RPS15a were related with gastric carcinoma to TNM stage and lymph node metastasis (Respectively, χ2=5.357, 4.688, P<0.05).
Conclusion
This study has successfully showed that high expression of SIRT2 and RPS15a in gastric carcinoma tissues, the overexpression of SIRT2 and RPS15a could participate in the biological behavior of gastric carcinoma.
Key words:
Immunohistochemical method; Gastric carcinoma; Silentmating information regulater 2; Ribosomal protein S15a
Objective
To investigate the expression of membrane-organizing extension spike protein (Moesin), thymidine kinase 1 (TK1) and the clinicopathological parameters of colorectal carcinoma.
Methods
The expression levels of Moesin and TK1 in 75 cases of colorectal carcinoma tissues and adjacent colorectal tissues were detected by immunohistochemistry.
Results
The expression rate of Moesin in colorectal carcinoma tissues was higher than that in non-cancerous adjacent colorectal tissues (68.00% vs. 21.33%, t=33.043, P=0.000). The expression levels of Moesin were correlated to histology grade, TNM stage and lymph node metastasis of colorectal carcinoma (respectively, t=4.733, P= 0.030; t=5.171, P= 0.023; t=8.549, P= 0.004). The expression rate of TK1 in colorectal carcinoma tissues was higher than that in non-cancerous adjacent colorectal tissues (80.00% vs. 13.33%, t=66.964, P=0.000). The expression levels of TK1 were correlated to serosa invasion, TNM stage and lymph node metastasis of colorectal carcinoma (respectively, t=1.781, P= 0.182; t=4.383, P= 0.036; t=7.748, P= 0.005).
Conclusion
Moesin and TK1 are associated with occurrence and development of colorectal carcinoma.
Key words:
Colorectal carcinoma; Immunohistochemical method; Membrane-organizing extension spike protein; Thymidine kinase 1
Research has demonstrated that apolipoprotein L1 (APOL1) has a role in the emergence and progression of a number of malignant cancers. It is unclear, however, how APOL1 functions in colorectal cancer (CRC). In this study, we examined the possible molecular processes underlying APOL1's biological role in CRC.
To analyse the effectiveness of age on HbA1c as a criterion for the diagnosis of diabetes in Chinese different age subjects.This retrospective study enrolled a total of 1147 outpatients with untreated newly diagnosed diabetes (aged 18-80 years, 42·55% women) from the Fujian Province, China, and 427 age and gender-matched (control) subjects without diabetes. Receiver operating characteristic curve (ROC) was plotted to determine the performance of HbA1c against results of oral glucose tolerance test (OGTT) performed at the same time according to specific age groups. The ORs and 95%CIs between diabetes and other metabolic disorders were analysed.(i) HbA1c provided an age-specific diagnosis for diabetes: there was a high diagnostic titter of HbA1c in the 18- to 39-year age group; conversely, there was a low diagnostic titter of HbA1c in the ≥70-year-old age groups. (ii) After adjusted for age, individuals with diabetes by OGTT criteria but not by WHO HbA1c criteria had an increased chance of having abnormal weight, hypertriglyceridaemia, HDL hypocholesterolaemia and insulin resistance. (iii) The diagnostic cut-off points of HbA1c for diabetes in different age groups (18-39, 40-49, 50-59, 60-69 and ≥70 years) were 6·1, 6·3, 6·4, 6·5 and 6·4, respectively. The age-specific HbA1c criteria exhibited the higher positive rate, sensitivity and lower false-negative rate when compared with WHO HbA1c criteria.This provided evidence indicating that there may be drawbacks in the use of HbA1c in the diagnosis of diabetes. Thus, we proposed that the impact of introducing HbA1c for diabetes diagnosis should be considered in terms of age. Cohort studies are needed to further confirm the suitability of age-specific HbA1c criteria for the diagnosis of diabetes.
Annexin A2 has been involved in cancer cell adhesion, invasion and metastasis. However, the exact function and mechanism of Annexin A2 in tumor progression of NSCLCs have not been elucidated. In this study, we showed that Annexin A2 was evidently overexpressed in human NSCLCs cell lines and NSCLCs tissues. Clinicopathologic analysis showed that Annexin A2 expression was significantly correlated with clinical stage, and lymph node metastasis. Kaplan-Meier analysis revealed that patients with high Annexin A2 expression had poorer overall survival rates than those with low Annexin A2 expression. Moreover, we found that knockdown of Annexin A2 significantly suppressed cell proliferation and invasion of NSCLCs cells. Mechanistically, our studies showed that knockdown of Annexin A2 increased the expression of p53, which in turn, induced cell cycle G2 arrest and inhibited epithelial-to-mesenchymal transition (EMT). Taken together, these data suggest that Annexin A2 plays an important role in NSCLCs progression, which could serve as a potential prognosis marker and a novel therapeutic target for NSCLCs.
To evaluate the association of early diarrhea and fecal volume with anastomotic leakage after low anterior resection (LAR) of rectal cancer.Clinical data of 541 patients with rectal cancer undergoing LAR at The Affiliated Hospital of Guangdong Medical College between January 2007 and January 2017 were analyzed retrospectively. Early postoperative diarrhea was defined as at least one occurrence of more than 50 ml watery stool or at least four times defecation per day within 7 days after surgery. The volume of fecal discharge from the transanal drain was measured at daily intervals for 3 days after surgery. Association of early diarrhea and anastomotic leakage was analyzed using logistic regression model. The accuracy of fecal volume in predicting anastomotic leakage was evaluated using receiver operating characteristics (ROC) curve.There were 319 males and 222 females with mean age of 59.3 years. Early postoperative diarrhea occurred in 99(18.3%) patients, and 41(7.6%) patients developed anastomotic leakage. The incidence of anastomodc leakage in patients with early diarrhea was significantly higher as compared to those without early diarrhea (15.2% vs. 5.9%, P=0.000). Multivariate analysis revealed that early diarrhea (OR=33.940, 95%CI: 8.423 to 89.240) and the distance between the tumor and the anal verge less than 7 cm (OR=13.085, 95%CI: 2.117 to 44.556) were independent risk factors for anastomotic leakage, while the presence of a transanal tube was an independent protective factor (OR=0.474, 95%CI: 0.122 to 0.881). The total fecal volume for 3 days after surgery was calculated in 162 patients with a transanal tube. The median fecal volume was 210 (100 to 4360) ml and 60 (0 to 480) ml in patients with and without anastomotic leakage respectively(P=0.000). ROC curve showed that the cut-off value of fecal volume for anastomotic leakage was 110 ml and the area under the curve was 0.824 with a high sensitivity of 85.7% and specificity of 81.3%.Early postoperative diarrhea after LAR procedure of rectal cancer may be an early predictor of anastomotic leakage, and fecal volume for 3 days after surgery ≥110 ml can accurately predict anastomotic leakage. Active prevention and management of early postoperative diarrhea may reduce the risk of anastomotic leakage.
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