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.

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.

Single tumor marker(TM)for cancer diagnosis with both satisfactory sensitivity and specificity has not been found.Therefore, it is necessary to identify the biomarkers to make the TM panel and establish the corresponding multiparameter predictive model through fuzzy mathematics methods.Recent studies using the big data technology showed that the integration of the biomarkers panel and prediction score model could provide the effective and accurate diagnosis for the cancer patients and be in favor of making the scheme for personalized therapy,treatment-monitoring and prognosis prediction.A reliable and efficient TM score prediction model will provide the novel perspectives and procedures for the diagnosis and treatment of cancer patients.

Objective:To establish a risk assessment model for recurrence and metastasis in patients with advanced nasopharyngeal carcinoma.Methods:A survival follow-up study was conducted using a COX regression model to analyze 242 patients with advanced nasopharyngeal carcinoma who were treated for the first time in the Fudan University Shanghai Cancer Center from March 1, 2012 to August 31, 2020. The mean age was (48.33±11.13) years, with 178 males and 64 females. The mean survival was (3.39±1.42) years. According to the random number table method, the enrolled subjects were divided into two groups, including 192 cases in the modeling group and 50 cases in the validation group. Venous blood was collected from patients before treatment, after the first treatment and during the follow-up period after treatment. The blood cell classification and blood biochemical indicators were analyzed. T test and Chi-square test were used to analyze the difference in indicators in prognosis of patients with recurrence and metastasis as the outcome of the study. Multivariate COX regression analysis was used to screen out the independent prognostic factors affecting the recurrence and metastasis of nasopharyngeal carcinoma patients, and the Nomogram models of recurrence and metastasis risk of patients in 2 years, 4 years and 6 years were constructed. The model C-Index of the modeling group and the validation group were calculated to evaluate the performance of the predictive model.Results:White blood cells ( P=0.028), lymphocyte counts ( P<0.001), neutrophils ( P=0.001), platelets ( P=0.046), albumin ( P<0.001), neutrophil/lymphocyte ratio ( P<0.001), platelet/lymphocyte ratio ( P<0.001), lymphocyte/monocyte ratio ( P<0.001), systemic immune inflammatory response index ( P<0.001), systemic inflammatory response index ( P<0.001), and prognostic nutritional index ( P=0.004) had statistically significant differences in the efficacy monitoring of patients; through multivariate COX regression analysis, it was found that the platelet/lymphocyte ratio ( HR 2.537, 95% CI 1.439-4.473) and the prognostic nutritional index ( HR 0.462, 95% CI 0.236-0.903) are important factors to predict the risk of recurrence and metastasis of patients. Combining the above indicators, the Nomogram risk assessment model was established. The C index of the modeling group was 0.698, and the C index of the validation group was 0.739. The calibration curves of the two groups showed good consistency. Conclusion:The Nomogram evaluation model can accurately predict the risk of recurrence and metastasis in patients with nasopharyngeal carcinoma, and provide a theoretical basis for evaluating the prognosis of clinical treatment.