Carcinogenesis is a multistep process that a couple of genes involve in the initiation of this disease.As a pivotal hallmark of cancer, the genomic instability ensues in which genetic alterations when this process was initialized and developed. With the increasing number of studies on genomic instability, the scientists pay more attentions on its biological function at post-genomic era. Genomic instability in various carcinomas is associated with broken telomere, gene modification, and contributes to the dysfunction of DNA damage and repair pathways.This review focus on the factors involved in genomic instability, as well the current detection methods of genomic instability and their clinical application.

Objective To evaluate application value of plasma tumor type M2 pyruvate kinase (TU M2-PK) in the treatment effect monitoring in breast cancer. Methods TU M2-PK was determined by ELISA in breast cancer patients (n = 63 ), benign breast disease patients (n = 22 ) and health controls (n = 40).The receiver operation characteristic (ROC) analysis was performed as compared with CA15-3 and CEA. Results ROC analysis showed the cut-off was set at 14. 1 U/ml for TU M2-PK ( sensitivity 46. 0% ;specificity 86. 0% ), and the diagnosis efficacy of TU M2-PK was higher than CA15-3 and CEA. The level of TU M2-PK was significantly higher in breast cancer patients (13. 3 U/ml) than that in health controls (7. 2 U/ml, U = 408. 5, P < 0. 05 ) and in benign breast disease patients ( 11.1 U/ml, U = 509.0,P < 0. 05 ). With the progression of breast carcinoma, the level of TU M2-PK as well as the positivity was increased. TU M2-PK concentration was higher in patients with lymph node metastasis (23. 3 U/ml ) than those without metastasis ( 10. 9 U/ml, U = 237. 0, P < 0. 01 ). The level of TU M2-PK correlated with therapy response. An elevated level of TU M2-PK was found preclinically in recurrent disease patients, and the levels decreased in the patients, which showed sensitive to chemotherapy. The TU M2-PK level was kept at baseline in patients with stable disease. Conclusion TU M2-PK is helpful in the diagnosis of breast cancer, and it is a valuable tumor marker for disease monitoring, therapy control and prognosis evaluation in breast cancer.

Liquid biopsy can non-invasively reveal the status of tumors and its prognosis in vivo, which is hotspots and difficulties of research in current era. Among them, an emerging marker called circulating tumor RNA (ctRNA) reflects the genetic information of tumor origin and provides a powerful basis for early diagnosis, targeted drug monitoring and prognosis prediction. At this stage, several ctRNA kits have been approved for clinical use. For example, microRNA (miRNA) can be used for aided diagnosis of liver cancer. And many transformation applications of promising ctRNA have been vigorously carried out. Despite the facts that there are still many clinical challenges of ctRNA detection technology to be solved effectively, ctRNA, as a new member of the liquid biopsy technology, has shown remarkable clinical value. Along with the mechanism becoming gradually clear, ctRNA will be a reliable diagnostic tool with the increasing clinical requirements for facilitating the tumor management.

Background and purpose: Human epidermal growth factor receptor 2 (HER-2) is the member of tyrosine kinase receptor family. Its differential expression plays the key role in choosing targeted drug for breast cancer. This study focused on screening the breast cancer cell clones of different HER-2 expression levels, and studying the bi-ological characteristics of these cells. Methods: Breast cancer SK-BR-3 cells were clonally purified, and the expression level of soluble HER-2 (sHER-2) from the culture supernatant was detected by the ECLIA on ADVIA Centaur CP System. Cell clones with high expression (>50.0 ng/mL), medium expression (15.8-50.0 ng/mL) and low expression (<15.8 ng/mL) of sHER-2 were identified, respectively. This study observed the morphological changes of cell strains with differential expression levels of sHER-2 by cell culture. Besides, biological characteristics were compared by a series of experiments in vitro, such as clone formation, scratch assay, and transwell detection. Results: Compared with normal breast cells, sHER-2 was overexpressed significantly in SK-BR-3 breast cancer cells. Furthermore, the abilities of clone formation, mobility and invasion of sHER-2 high expression cell strain [(51.3±3.4)%, (50.0±0.6)% and (53.5±4.2)%] were signifi-cantly higher than those of sHER-2 medium expression [(42.0±3.7)%, (19.5±3.4)% and (33.2±3.9)%] or sHER-2 low expression [(26.7±2.9)%, (13.6±1.0)% and (28.9±5.4)%], and the differences were all statistically significant (P<0.05). Conclusion: Breast cancer cell strain with high expression level of sHER-2 can enhance cell proliferation, promote cell motility and other biological effects, which may lay the foundation for clinical screening of targeted drug therapies for breast cancer.

Liquid biopsy can non-invasively reveal the status of tumors in vivo, and provides a powerful basis for early diagnosis, personalized treatment monitoring and prognosis prediction. According to the type of tumor-associated material, liquid biopsy covers circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs) and circulating tumor RNA (ctRNA) etc. At present, several liquid biopsy products havebeen approved for clinical use, while many transformation studies have been vigorously carried out. However, there are still many clinical challenges to be solved effectively. Despite the standardization of detection and quality management system of liquid biopsy are lagged with the rapid development of technology, liquid biopsy, as a highly promising detection technology, will become a reliable diagnostic tool with the increasing clinical requirements for facilitating the tumor management.

Objective:To investigate the clinical value of glypican-3 (GPC3) detection in the diagnosis and therapy-monitoring of primary hepatocellular carcinoma (HCC).Methods:From March 2018 to May 2019, the patients with HCC were enrolled as the experimental group( n=166)from Fudan University Shanghai Cancer Centre, while the specimens from health control group( n=94) and benign control group ( n=50) were analyzed. The serum of GPC3 and alpha fetoprotein (AFP)levels were respectively detected by ELISA and chemiluminescence. GPC3 detections combined with AFP etc. in accuracy of HCC diagnosis were explored by using Logistic regression analysis. Results:The serum GPC3 level in patients with HCC ［0.210 (0.048, 0.801)mg/L］ ［Median (quartile Q1, Q3)］ was significantly higher than those in healthy controls ［0.029(0.019, 0.052)mg/L］ and benign controls ［0.033(0.021, 0.043) mg/L］ ( Z=-7.69, P<0.001).The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AFP were significantly different among the three groups ( Z=-7.02, -6.85, -8.36 respectively, P<0.001). Among the serological indicators, it was related to ALT and AST ( Z=-3.77, -4.09 respectively, P<0.001).The Cut-off level of GPC3 was determined as 0.077 mg/L by ROC curve. The sensitivity of the combined detection of serum GPC3 with AFP for HCC was up to 87.82%, the specificity was 77.86%, the negative predictive value was 84.29%, and the positive predictive value was 82.53%.The HCC-GPC3 model was constructed by using Logistic regression analysis. The area under the ROC curve was 0.882, the total sensitivity was 91.10%, and the total specificity was 72.73%. Further analysis showed that the serum GPC3 of patients with HCC was significantly lower ［0.454(0.019, 0.286) mg/L］ than that before surgery［0.608(0.039, 0.554）mg/L］( Z=-7.32, P<0.001). Conclusion:The detection of serum GPC3 can be applied to aid diagnosis and therapy-monitoring of HCC.The combination of GPC3 and AFP can improve the diagnostic efficiency of HCC.

Objective:To discuss the diagnostic value of calcitonin(CT), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), pro-gastrin releasing peptide (Pro-GRP) and chromogranin A (CgA) in the identification of medullary thyroid carcinoma (MTC).Methods:The CT levels in 105 cases of MTC, 50 cases of papillary thyroid carcinoma, 10 cases of thyroid follicular carcinoma, 5 cases of undifferentiated thyroid carcinoma, 50 cases of benign thyroid diseases, 30 cases of non-thyroid malignant tumors and 50 cases of healthy controls were measured from February 2017 to August 2019 at the Department of Clinical Laboratory, Cancer Hospital affliated to Fudan University. Additionally, 79 cases of MTC, 30 cases of non-MTC thyroid malignant tumors and 30 healthy controls were selected for the measurement of CEA, NSE, Pro-GRP and CgA levels. The receiver operating curve was utilized to clarify the area under the curve (AUC), sensitivity, and specificity of each indicator to distinguish between different groups.Results:The medians of CT concentrations in the group of MTC patients was 607.2 (152.5,2 777.5)pg/ml, which was statistically significantly higher than that of the subjects in the group of papillary thyroid carcinoma 1.48 (0.5,2.91)pg/ml, follicular thyroid carcinoma 1.90 (0.82,2.99)pg/ml, undifferentiated thyroid carcinoma 0.50 (0.50,4.93)pg/ml, benign thyroid disease 1.30 (0.50,2.79)pg/ml, non-thyroid malignancies 1.36 (0.50,2.89)pg/ml and healthy controls 2.05 (0.89,3.18)pg/ml. The sensitivity, specificity and AUC of CT to distinguish MTC vs. non-MTC patients was 96.2%, 99.3% and 0.99, respectively. The maximum diameter (>1 cm, P=0.001, OR=15.74) and number (>1, P=0.04, OR=3.4) of nodules were two independent risk factors for elevated CT. CEA (AUC=0.94), NSE (AUC=0.65), Pro-GRP (AUC=0.94) and CgA (AUC=0.83) could all distinguish MTC vs. non-MTC thyroid malignancies. The AUC, sensitivity and specificity by combining CT, CEA, NSE, Pro-GRP and CgA to differentiate MTC vs. non-MTC thyroid malignancies was 1, 100% and 100%, respectively. Conclusions:CT, CEA, NSE, Pro-GRP and CgA may be helpful for the auxiliary diagnosis of MTC. The combination of these indicators in the diagnosis of MTC has high sensitivity and specificity.

Objective:To investigate the clinical value of glypican-3 (GPC3) detection in the diagnosis and therapy-monitoring of primary hepatocellular carcinoma (HCC).Methods:From March 2018 to May 2019, the patients with HCC were enrolled as the experimental group( n=166)from Fudan University Shanghai Cancer Centre, while the specimens from health control group( n=94) and benign control group ( n=50) were analyzed. The serum of GPC3 and alpha fetoprotein (AFP)levels were respectively detected by ELISA and chemiluminescence. GPC3 detections combined with AFP etc. in accuracy of HCC diagnosis were explored by using Logistic regression analysis. Results:The serum GPC3 level in patients with HCC ［0.210 (0.048, 0.801)mg/L］ ［Median (quartile Q1, Q3)］ was significantly higher than those in healthy controls ［0.029(0.019, 0.052)mg/L］ and benign controls ［0.033(0.021, 0.043) mg/L］ ( Z=-7.69, P<0.001).The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AFP were significantly different among the three groups ( Z=-7.02, -6.85, -8.36 respectively, P<0.001). Among the serological indicators, it was related to ALT and AST ( Z=-3.77, -4.09 respectively, P<0.001).The Cut-off level of GPC3 was determined as 0.077 mg/L by ROC curve. The sensitivity of the combined detection of serum GPC3 with AFP for HCC was up to 87.82%, the specificity was 77.86%, the negative predictive value was 84.29%, and the positive predictive value was 82.53%.The HCC-GPC3 model was constructed by using Logistic regression analysis. The area under the ROC curve was 0.882, the total sensitivity was 91.10%, and the total specificity was 72.73%. Further analysis showed that the serum GPC3 of patients with HCC was significantly lower ［0.454(0.019, 0.286) mg/L］ than that before surgery［0.608(0.039, 0.554）mg/L］( Z=-7.32, P<0.001). Conclusion:The detection of serum GPC3 can be applied to aid diagnosis and therapy-monitoring of HCC.The combination of GPC3 and AFP can improve the diagnostic efficiency of HCC.

Objective:To discuss the diagnostic value of calcitonin(CT), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), pro-gastrin releasing peptide (Pro-GRP) and chromogranin A (CgA) in the identification of medullary thyroid carcinoma (MTC).Methods:The CT levels in 105 cases of MTC, 50 cases of papillary thyroid carcinoma, 10 cases of thyroid follicular carcinoma, 5 cases of undifferentiated thyroid carcinoma, 50 cases of benign thyroid diseases, 30 cases of non-thyroid malignant tumors and 50 cases of healthy controls were measured from February 2017 to August 2019 at the Department of Clinical Laboratory, Cancer Hospital affliated to Fudan University. Additionally, 79 cases of MTC, 30 cases of non-MTC thyroid malignant tumors and 30 healthy controls were selected for the measurement of CEA, NSE, Pro-GRP and CgA levels. The receiver operating curve was utilized to clarify the area under the curve (AUC), sensitivity, and specificity of each indicator to distinguish between different groups.Results:The medians of CT concentrations in the group of MTC patients was 607.2 (152.5,2 777.5)pg/ml, which was statistically significantly higher than that of the subjects in the group of papillary thyroid carcinoma 1.48 (0.5,2.91)pg/ml, follicular thyroid carcinoma 1.90 (0.82,2.99)pg/ml, undifferentiated thyroid carcinoma 0.50 (0.50,4.93)pg/ml, benign thyroid disease 1.30 (0.50,2.79)pg/ml, non-thyroid malignancies 1.36 (0.50,2.89)pg/ml and healthy controls 2.05 (0.89,3.18)pg/ml. The sensitivity, specificity and AUC of CT to distinguish MTC vs. non-MTC patients was 96.2%, 99.3% and 0.99, respectively. The maximum diameter (>1 cm, P=0.001, OR=15.74) and number (>1, P=0.04, OR=3.4) of nodules were two independent risk factors for elevated CT. CEA (AUC=0.94), NSE (AUC=0.65), Pro-GRP (AUC=0.94) and CgA (AUC=0.83) could all distinguish MTC vs. non-MTC thyroid malignancies. The AUC, sensitivity and specificity by combining CT, CEA, NSE, Pro-GRP and CgA to differentiate MTC vs. non-MTC thyroid malignancies was 1, 100% and 100%, respectively. Conclusions:CT, CEA, NSE, Pro-GRP and CgA may be helpful for the auxiliary diagnosis of MTC. The combination of these indicators in the diagnosis of MTC has high sensitivity and specificity.

Background and purpose:The plasma used for routine coagulation test(CCT)can only reflect a single component at a certain coagulation time point/segment,while thromboelastography(TEG)can depict the overall dynamic process curve of coagulation and fibrinolysis,which can more independently and completely reflect the true state of the blood and can serve as a supplement to coagulation function testing.This study aimed to evaluate the application value of combined coagulation function indexes in monitoring the hypercoagulable state of patients with colorectal cancer after chemotherapy,and to explore the risk factors of thrombosis in patients with colorectal cancer after chemotherapy,so as to provide reference for clinical monitoring of hypercoagulable state.Methods:A total of 160 patients with colorectal cancer from Fudan University Shanghai Cancer Center from June 2021 to June 2023 were selected as the experimental group,and 80 healthy subjects were selected as the control group.Then the experimental group was divided into a group without thrombosis(82 cases)and a group with thrombosis(78 cases)according to whether they had thrombosis or not.The determinations of thromboelastography(TEG)[coagulation reaction time(R),coagulation formation time(K),blood clot formation rate(α-Angle),maximum amplitude(MA)and coagulation index(CI)],conventional coagulation tests(CCT)[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(Fib),D-dimer(DD),fibrinogen degradation products(FDP)]and platelet count(PLT)were studied among three groups.With or without thrombosis as the criterion of hypercoagulable state,statistically significant indicators were selected to be included in the binary logistic regression analysis,and the receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of single and combined detection of the coagulation function indicators for hypercoagulable state in patients with colorectal cancer after chemotherapy.Basic information,tumor stage and Autar score of deep vein thrombosis were collected in 160 patients with colorectal cancer.Logistic regression analysis was performed to explore the risk factors of thrombosis.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(number:050432-4-2108*).Results:Compared with the control group,the R,TT and PLT of the group with thrombosis were decreased(P＜0.05),while APTT,PT,DD and FDP were increased(P＜0.05).The differences in various indicators between the group with thrombosis and the control group were statistically significant(P＜0.05).Compared with the group without thrombosis,the K in the group with thrombosis decreased(P＜0.05),while Angle,MA,CI,FIB,DD and FDP all increased(P＜0.05).ROC curve analysis showed that in the assessment of hypercoagulable state in patients with colorectal cancer after chemotherapy,the area under curve(AUC)of TEG was 0.756,sensitivity was 67.5%,and specificity was 73.8%.The AUC of CCT was 0.691,sensitivity was 78.8%,and specificity was 56.2%.The combined detection AUC was 0.840,sensitivity was 80.0%,and specificity was 77.5%.In the analysis of risk factors,tumor stage,distant metastasis and Autar score were correlated with thrombus formation in patients with colorectal cancer after chemotherapy(P＜0.05),and the differences of the three risk factors in K,Angle,MA,CI,Fib,DD and FDP were statistically significant(P＜0.05).Conclusion:K,Angle,MA,CI,Fib,DD and FDP are the main indicators to reflect the hypercoagulable state,and the combined detection of TEG and CCT can better reflect the coagulation state of patients with colorectal cancer after chemotherapy.Tumor stage Ⅲ to Ⅳ,distant metastasis and high Autar score are risk factors for thrombosis.The incidence of thrombosis can be reduced by monitoring the relevant coagulation indicators in the high-risk population.