Etiological Analysis,Psychological Assessment And Novel Tumor Biomarker Investigation In Patients With Colorectal Cancer

BackgroundColorectal cancer(CRC)is the most common gastrointestinal malignancies in humans,with the third highest mortality worldwide.Due to the robust development of economy and the change of diet style,the population of CRC patients grow rapidly with increasing mortality rate in China.The occurrence of CRC is affected by environmental factors.Potential environmental exposure factors include dietary factors,lifestyle,mental and psychological factors,etc.Unfortunately,the evaluation systems adopted by the investigators from different countries,regions and populations are quite inconsistent among the current studies.No wide-accepted consensus of CRC risk/protective factors has been reached nowadays.The therapeutic approaches of CRC include resection operations at first and then followed by chemotherapy and radiotherapy,if possible.The maligancies as well as the suffering procedure of diagnosis and treatment not only cause physical damage to the patients,but also lead to traumatic psychology or even post-traumatic stress disorders.Anxiety and depression are the most common psychological forms of stresses for the CRC patient.Of note,depression is the independent risk factors of CRC patient mortality.Therefore,it's reasonable to add psychological therapy into the comprehensive treatment of CRC.However,the psychological problems of cancer patients are often neglected nowadays.There are few studies focusing on the perioperative anxiety and depression of the CRC patients in China.Early diagnosis and treatment of CRC is vital and basic to improve the prognosis,quality of life and psychological condition of CRC patients.However,the current clinical diagnostic arsenal of CRC is quite limited.MicroRNAs(miRNAs)modulate the occurrence and development of tumors,which have become a focus in transitional research.The circulating miRNAs derived from tumor cells are characterized by high specificity and sensitivity in tumor detection.Morevoer,they are stable in the peripheral blood(serum or plasma).Our previous study revealed that miR-210 was highly expressed in local CRC tissues and played an important role in promoting cancer.However,the expression pattern and clinical application of circulating miR-210 as a circulating tumor biomarker in CRC patients have not been reported yet.The ultimate goal of the treatment of CRC patients should be not only to eliminate the malignancy and prolonging life,but also improve the life quality and mental health status,in order to realize early prevention,early intervention and early treatment.This study mainly focused on the epidemic factors of CRC tumorogenesis,the perioperative psychological assessment of the patients and their influencing factors,and find new biomarker which can assist early diagnosis of CRC.Part ?.The etiological factors of colorectal cancer patients PurposeThe risk factors and protective factors of CRC were studied to provide theoretical basis for the prevention and treatment of CRC in ShandongMethods317 cases of CRC patients from Qilu Hospital of Shandong University and 317 controlled healthy individuals were investigated.A pre-verification was conducted to clarify the accuracy of this investigation.The correlations of factors including dietary habits,life styles,psychological and environment variables to the tumor was retrospectively anazlyzed between the two populations.Using univariate Logistic regression analysis,the related factors affecting the incidence of colorectal cancer were screened out.The factors with statistical significance were incorporated into the further multivariate conditional Logistic regression analysis.Considered that the potential risk factors of colon cancer might be different from those of rectal cancer,stratified analysis was used to evaluate predictors of colon and rectal cancer respectively.Results1.The univariate Logistic regression analysis revealed that high body mass index(BMI),high frequency of pork,animal oil,fried food,high-temperature barbecue meat,the smoked foods,cured fish and pork consumption,smoking,alcohol abuse,psychosis,living near a factory,depression and poor sleep quality were risk factors of CRC(all P<0.05),with OR values of 2.909,1,865,1.270,3.310,2.863,1.517,1.287,1.906,1.464,2.299,3.828,1.671,8.631 and 1.461,respectively.The high intake frequency of fresh vegetables(fiber),fresh fruit,garlic consumption and physical exercise were the protective factors of CRC(all P<0.05),and their OR values were 0.350,0.788,0.497 and 0.681,respectively.2.Multivariate regression analysis showed that high BMI,high frequency of pork,fried food,barbecue meat consumption,alcohol,psychosis,living near a factory and depression were independent risk factors for CRC(P<0.05),with OR values of 2.038,1.587,3.630,2.621,2.390,3.165,5.302 and 13.954.The intake frequency of fresh vegetable(fiber),garlic,and physical exercise were independent protective factors for CRC(P<0.05),with OR values of 0.247,0.499 and 0.232?3.Stratified Analysis revealed that frequency of fresh vegetable consumption(fiber),living near a factory,depression and physical exercise are the influential factors of CRC(P<0.05).BMI(P=0.033),frequency of fried food consumption(P<0.001),frequency of barbecue meat consumption(P<0.001)and frequency of garlic consumption(P<0.001)were the influential factors of colon cancer.Alcohol(P=0.009)and psychosis(P=0.019)were the influential factors of rectal cancer.ConclusionThe incidence of CRC in Shandong is closely related to non-healthy diet habits,bad life styles,environmental pollution and mental factors.Clarifying the risk and protective factors of CRC and targeted education and intervention are important to reduce the incidence of CRC in Shandong.Part ?.Perioperative psychological assessment and analysis of CRC patientsPurposePsychological assessments were made to the peri-opertative anxiety and depression of the CRC patients.By analyzing the influencing factors,the necessity of psychological therapy is confirmed.MethodsHospital Anxiety and Depression Scale(HADS),the Life Orientation Test-Revised(LOT-R),Multidimensional Scale of Perceived Social Support(MSPSS),Quality of Life Questionnaire-Core30 of the European Organization for Research and Treatament(EORTC QLQ-C3 0)in addition to the general population questionnaire were used to collect the data of the peri-operative anxiety and depression of the CRC patients.The relationship between the optimism,social support and quality of life with anxiety and depression was assessed by the Pearson correlation analysis.The influential factors of anxiety and depression in CRC patients before the resection were analyzed by the multivariate Logistic regression model.The influential factors of the degree of anxiety and depression in CRC patients after the resection were analyzed by the multivariate linear regression model.Results1.In 127 patients with CRC,the pre-operative anxiety score of the HADS scale was 8.78(SD 3.95)and the pre-operative depression score of the HADS scale was 8.07(SD 4.45).58.3%of the patients had anxiety symptoms and 50.4%had depressive symptoms before surgery.In contrast,90.6%of 53 patients who received the surgery had anxiety symptoms and 88.7%had depressive symptoms.2.Correlation analysis showed that among 127 patients with CRC before surgery,depression was highly positive correlated with anxiety(P<0.001).Optimism,social function,role function,emotional function,friend support,other important support and social support were significantly negative correlated with anxiety(P<0.001).Optimism,role function,social function,friend support,other support and social support were significantly negative correlated with depression(P<0.001).Univariate analysis of differences exhibited the statistical significance(P<0.05)among anxiety scores of patients with different genders,age,occupations and pathological types.Meanwhile,statistical significance among depression scores of patients with different genders,age and TNM stages was established(P<0.05).In the multivariate Logistic regression analysis,the anxiety influential factors of female,unemployed and optimism were included into the Logistic regression model.The regression equation of anxiety in patients with CRC is as followed:P=Exp(3.858+1.587*femal+1.479*unemployed-0.404*optimism score)/(1+Exp(3.858+1.587*female+1.479*unemployed-0.404*optimism score))The depression influential factors of role function and optimism were included into the Logistic regression model.The regression equation of depression in patients with CRC is as followed:P=Exp(12.652-0.038*the score of role function-0.529*optimism score)/(1+Exp(12.652-0.038*the score of role function-0.529*optimism score))3.Correlation analysis revealed that depression was highly positive correlated with anxiety in 53 CRC patients who had received surgery(P<0.001).Optimism,somatic function,role function,emotional function and cognitive function were significantly negative correlated with anxiety(P<0.001).Optimism,cognitive function,role function and physical function were significantly negative correlated with depression(P<0.001).Univariate analysis of difference revealed the statistical significance(P<0.05)among anxiety scores of patients with different genders and level of education(P<0.05).In the multivariate linear regression analysis,the anxiety influential factors of female,optimism,role function and emotional function were included into the multivariate linear regression model.The depression influential factors of optimism and cognitive function were included into the multivariate linear regression model.ConclusionPeri-operative anxiety and depression are common complications for the CRC patients.The severity was affected by protective factors and risk factors.Thus,physicians should pay more attention to the mental status of their patients and intervene early if necessary.Part ?.Clinical significance of circulating miR-210 in colorectal cancerPurposeWe aimed to investigate the clinical significance of circulating miR-210 as a non-invasive diagnostic biomarker in the serum of the CRC patients.MethodsSerum samples from 268 CRC patients and 102 healthy donors were collected.The serum levels of miR-210 from both groups were then detected by RT-qPCR.The correlations between miR-210 expression and involved clinicopathological parameters were analyzed.The receiver operating characteristic(ROC)curve analysis in comparison with the conventional biomarker CEA were applied to test the diagnostic efficacy of circulating miR-210 levels for CRC.Kaplan-Meier survival curve and Cox proportional hazards regression model were used to analyze the prognostic value of circulating miR-210 in CRC.Results1.The expression of serum miR-210 in CRC patients was significantly higher than that of healthy donors(P<0.001).In addition,the serum miR-210 level in TNM stage I patients was significantly lower than that in TNM stage ?-? patients(P<0.05).2.The area under the ROC curve of serum miR-210 in CRC patients was 0.821(95%CI:0.778-0.859),with a sensitivity of 74.6%(95%CI:69.0%-79.7%)and a specificity of 73.5%(95%CI:63.9%-79.7%).In contrast,the area under the ROC curve of CEA was 0.701(95%CI:0.651-0.747,P<0.05).The area under the ROC curve of serum miR-210 was significantly higher than that of serum CEA.3.Kaplan-Meier survival analysis showed that patients with high levels of circulating miR-210 had significantly worse overall survival(OS)and disease free survival(DFS)rates,compared with patients with low levels of circulating miR-210(all P<0.05).Using Cox proportional hazard model analysis,we found that the expression level of miR-210(HR=2.767;95%CI,1.307-5.857;P=0.008)was an independent prognostic factor for overall survival in CRC patients;the expression level of miR-210(HR=2.608;95%CI,1.280-5.314;P=0.008)was an independent prognostic factor for disease-free survival in patients with CRC.ConclusionMiR-210 was highly expressed in serum of patients with CRC.Its expression level gradually increased with the progress of clinical stage.The diagnostic value of circulating mir-210 was superior to traditional CRC biomarker CEA.As an independent prognostic factor,its expression was negatively correlated with the prognosis of patients.Our results suggested that circulating miR-210 as a new biomarker of CRC was of promising transtional value,which could be helpful for early detection and prognostic evaluation of CRC.