1.CDK5-triggered G6PD phosphorylation at threonine 91 facilitating redox homeostasis reveals a vulnerability in breast cancer.
Yuncheng BEI ; Sijie WANG ; Rui WANG ; Owais AHMAD ; Meng JIA ; Pengju YAO ; Jianguo JI ; Pingping SHEN
Acta Pharmaceutica Sinica B 2025;15(3):1608-1625
Glucose-6-phosphate dehydrogenase (G6PD), the first rate-limiting enzyme of the pentose phosphate pathway (PPP), is aberrantly activated in multiple types of human cancers, governing the progression of tumor cells as well as the efficacy of anticancer therapy. Here, we discovered that cyclin-dependent kinase 5 (CDK5) rewired glucose metabolism from glycolysis to PPP in breast cancer (BC) cells by activating G6PD to keep intracellular redox homeostasis under oxidative stress. Mechanistically, CDK5-phosphorylated G6PD at Thr-91 facilitated the assembly of inactive monomers of G6PD into active dimers. More importantly, CDK5-induced pho-G6PD was explicitly observed specifically in tumor tissues in human BC specimens. Pharmacological inhibition of CDK5 remarkably abrogated G6PD phosphorylation, attenuated tumor growth and metastasis, and synergistically sensitized BC cells to poly-ADP-ribose polymerase (PARP) inhibitor Olaparib, in xenograft mouse models. Collectively, our results establish the crucial role of CDK5-mediated phosphorylation of G6PD in BC growth and metastasis and provide a therapeutic regimen for BC treatment.
2.Clinical efficacy of radical resection for lung metastasis from colorectal cancer and prognostic factors analysis
Pengju CHEN ; Tingting SUN ; Yunfeng YAO ; Yifan PENG ; Jun ZHAO ; Aiwen WU
Chinese Journal of Digestive Surgery 2021;20(3):301-305
Objective:To explore the clinical efficacy of radical resection for lung metastasis from colorectal cancer and the prognostic factors.Methods:The retrospective cohort study was conducted. The clinicopathological data of 63 colorectal cancer patients with lung metastasis who were admitted to Peking University Cancer Hospital from January 2004 to December 2015 were collected. There were 35 males and 28 females, aged (57±12)years. Patients underwent radical resection for primary lesion and lung metastasis from colorectal cancer. Observation indicators: (1) diagnosis and treatment; (2) follow-up and survival; (3) prognostic factors analysis. Follow-up was conducte by outpatient examination and telephone interview to detect the survival of patients after operation up to December 2018. Measurement data with normal distribution were represented as Mean±SD, and measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. Log-rank test was used for univariate analysis and COX proportional hazard model was used for multivariate analysis. Results:(1) Diagnosis and treatment: of 63 patients with lung metastasis from colorectal cancer, 6 had synchronous lung metastasis and 57 had metachronous lung metastasis. Eighteen cases of suspected lung metastasis were initially detected by chest X-ray, and further confirmed by computed tomography (CT). Forty-five cases of suspected lung metastasis were initially detected by chest CT. All the 63 patients underwent radical resection for primary and metastatic lesions. Two of 22 cases undergoing mediastinal lymph nodes dissection were detected one positive lymph node, respectively. All patients recovered well after operation, without severe complications. There were 57 of 63 patients receiving more than 6 months of postoperative adjuvant chemotherapy and targeted therapy based on fluorouracils. (2) Follow-up and survival: 63 patients were followed up for 8-143 months, with a median follow-up time of 58 months. During the follow-up, 19 of 63 patients died, 24 patients had secondary recurrence with a 5-year recurrence rate of 38.1%(24/63) and a recurrence interval of 18 months(range, 3-58 months). Of 24 patients with secondary recurrence, 19 had lung metastasis, 3 had brain metastasis, 2 had bone metastasis, 2 had liver metastasis; some patients had multiple metastases. Of 24 patients with secondary recurrence, 5 underwent reoperation and 19 underwent chemotherapy and radiochemotherapy. The 5-year overall survival rate of 63 patients was 62.7%. (3) Prognostic factors analysis: results of univariate analysis showed that location of primary lesion, the number of lung metastases and carcinoembryonic antigen (CEA) level before resection of lung metastasis were related factors for prognosis of patients with lung metastasis from colorectal cancer ( χ2=4.162, 7.175, 6.725, P<0.05). Results of multivariate analysis showed that the number of lung metastases and CEA level before resection of lung metastasis were independent influencing factors for prognosis of patients with lung metastasis from colorectal cancer ( hazard ratio=2.725, 2.778, 95% confidence interval as 1.051-7.064, 1.072-7.021, P<0.05). Conclusions:Radical resection for lung metastasis from colorectal cancer is safe and feasible. The number of lung metastases and CEA level before resection for lung metastasis are independent influencing factors for prognosis of patients with lung metastasis from colorectal cancer.
3.Application of micellar electrokinetic capillary chromatography for identification, quantitative detection and unfolding analysis of interleukin-12.
Pengju BAO ; Yao SUN ; Haihua WANG ; Xiaoju JIN ; Genbao ZHANG
Journal of Southern Medical University 2020;40(9):1301-1306
OBJECTIVE:
To establish a micellar electrokinetic capillary chromatography-based method for identification and quantitative detection of interleukin-12 (IL-12) and analysis of its unfolding process.
METHODS:
An uncoated fused-silica capillary (inner diameter 50 μm) with a total length of 48.5 cm (40 cm to the detector) was used for the experiment. The factors influencing the separation efficiency of IL-12 were analyzed, and a standard curve of IL-12 concentration was established. The mixture of IL-12 and anti-IL-12 antibody was incubated in a water bath at 38 ℃ for 40 min, and capillary electrophoresis was then performed under the same conditions. The results were compared with those of IL-12 and anti-IL-12 antibody to identify IL-12. IL-12 and dithiothreitol (DTT) were incubated at 60 ℃ in water bath for different lengths of times, and the unfolding process of IL-12 was analyzed based on electrophoresis results of IL-12 in different states.
RESULTS:
A micellar capillary electrophoresis on-line sweep method was established with 80 mmol/L borate (pH=9.3) containing 30 mmol/L sodium dodecyl sulfate (SDS) as the buffer solution. This system showed a good linear relationship between the peak area and the mass concentration of IL-12 with a linear correlation coefficient of 0.9991 within the linear range of 2 to 120 ng/L. As the incubation time of IL-12 and DTT prolonged, the disulfide bond of IL-12 gradually opened and resulted in distinct changes in the protein peak.
CONCLUSIONS
This capillary electrophoresis-based method is simple and sensitive for IL-2 analysis and allows rapid detection of changes in IL-12 content in the setting of tumors and analysis of the possible causes.
4. "Watch and wait" strategy after neoadjuvant therapy for rectal cancer: status survey of perceptions, attitudes and treatment selection in Chinese surgeons
Tingting SUN ; Lin WANG ; Yunfeng YAO ; Yifan PENG ; Jun ZHAO ; Tiancheng ZHAN ; Jiahua LENG ; Hongyi WANG ; Nan CHEN ; Pengju CHEN ; Yingjie LI ; Xiao ZHANG ; Xinzhi LIU ; Yue ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2019;22(6):550-559
Objective:
To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT).
Methods:
A cross
5."Watch and wait" strategy after neoadjuvant therapy for rectal cancer: status survey of perceptions, attitudes and treatment selection in Chinese surgeons
Tingting SUN ; Lin WANG ; Yunfeng YAO ; Yifan PENG ; Jun ZHAO ; Tiancheng ZHAN ; Jiahua LENG ; Hongyi WANG ; Nan CHEN ; Pengju CHEN ; Yingjie LI ; Xiao ZHANG ; Xinzhi LIU ; Yue ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2019;22(6):550-559
Objective To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods A cross?sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture?level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing"watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of"watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher′ s exact test for categorical variables. Results Forty?eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3?year disease?free survival of patients with ypCR in their own hospitals. Fifty?five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over?treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%, 70/77) and DWI?MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well?differentiated adenocarcinoma (68.8%, 53/77). Sixty?six surgeons (85.7%) believed that long?term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine+oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty?one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty?four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non?metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty?two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus?preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty?nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty?six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow?up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty?one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty?six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions Chinese surgeons seem to have inadequate knowledge of non?operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non?operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.
6."Watch and wait" strategy after neoadjuvant therapy for rectal cancer: status survey of perceptions, attitudes and treatment selection in Chinese surgeons
Tingting SUN ; Lin WANG ; Yunfeng YAO ; Yifan PENG ; Jun ZHAO ; Tiancheng ZHAN ; Jiahua LENG ; Hongyi WANG ; Nan CHEN ; Pengju CHEN ; Yingjie LI ; Xiao ZHANG ; Xinzhi LIU ; Yue ZHANG ; Aiwen WU
Chinese Journal of Gastrointestinal Surgery 2019;22(6):550-559
Objective To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods A cross?sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture?level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing"watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of"watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher′ s exact test for categorical variables. Results Forty?eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3?year disease?free survival of patients with ypCR in their own hospitals. Fifty?five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over?treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%, 70/77) and DWI?MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well?differentiated adenocarcinoma (68.8%, 53/77). Sixty?six surgeons (85.7%) believed that long?term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine+oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty?one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty?four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non?metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty?two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus?preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty?nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty?six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow?up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty?one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty?six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions Chinese surgeons seem to have inadequate knowledge of non?operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non?operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.
7.Effect of adjuvant chemotherapy on the prognosis of stage II( colon cancer patients with high risk factors.
Aiwen WU ; Pengju CHEN ; Tingting SUN ; Xinyu WANG ; Xinzhi LIU ; Yunfeng YAO
Chinese Journal of Gastrointestinal Surgery 2017;20(12):1381-1386
OBJECTIVETo investigate the effect of adjuvant chemotherapy on the prognosis of stage II( colon cancer patients with high risk factors.
METHODSClinicopathological and follow-up data of stage II( colon cancer patients undergoing radical surgery from January 2001 to March 2012 at Gastrointestinal Cancer Center of Peking University Cancer Hospital were retrospectively analyzed. The effect of adjuvant chemotherapy (within postoperative 2 month, fluorine uracil as main drugs) on the prognosis of high-risk patients was analyzed. High risk factors were defined as having at least one of the following factors: (1) tumor stage T4; (2) poor differentiation; (3) with vascular cancer embolus; (4) number of harvested lymph node less than 12; (5) complicated with obstruction or perforation.
RESULTSA total of 497 patients with stage II( colon cancer were included in this study, of whom 258 cases(51.9%) had high risk factors, including stage T4 tumor in 80 cases(16.1%), poor differentiation in 80 cases (16.1%), cancer embolus in 37 cases (7.4%), lymph node harvested number less than 12 in 88 cases (17.7%), and obstruction or perforation in 85 cases (17.1%). Among 497 patients, number of cases with 1 to 4 high risk factors was 170 (34.2%), 68 (13.7%), 16 (3.2%) and 4 (0.8%), respectively. The last follow-up time was December 2016. The 5-year overall survival rate of all the 497 patients was 81.7%. The 5-year overall survival rate of 239 patients without high risk factors was 87.0%. The 5-year survival rate in patients with 1 to 4 risk factors was 81.9%, 73.7%, 66.7% and 25.0%, respectively (P=0.001). There was no significant difference in 5-year survival rate between 103 patients with adjuvant chemotherapy and 394 patients without adjuvant chemotherapy (79.6% vs. 82.8%, P=0.814). In patients with high risk factors, 80(31.0%) received adjuvant chemotherapy. There was no significant difference of 5-year survival rate between 80 patients with adjuvant chemotherapy and 178 patients without adjuvant chemotherapy (81.4% vs. 74.7%, P=0.147). Multivariate analysis showed that preoperative CEA level, T4 stage, lymph node harvested number, and tumor differentiation were the independent prognostic factors of patients with stage II( colon cancer (all P<0.05).
CONCLUSIONSThe proportion of patients with at least one risk factor is quite high in stage II( colon cancer cases. Adjuvant chemotherapy can not prolong the overall survival time of high risk patients.
8.Retrospective analysis of 856 cases with stage 0 to III rectal cancer underwent curative surgery combined modality therapy.
Pengju CHEN ; Yunfeng YAO ; Jun ZHAO ; Ming LI ; Yifan PENG ; Tiancheng ZHAN ; Changzheng DU ; Lin WANG ; Nan CHEN ; Jin GU ; Email: ZLGUJIN@126.COM.
Chinese Journal of Surgery 2015;53(7):496-501
OBJECTIVETo investigate the survival and prognostic factors of stage 0 to III rectal cancer in 10 years.
METHODSClinical data and follow-up of 856 rectal cancer patients with stage 0-III underwent curative surgery from January 2000 to December 2010 were retrospective analyzed. There were 470 male and 386 female patients, with a mean age of (58 ± 12) years. Kaplan-Meier method was used to analyze the overall survival and disease free survival. Log-rank test was used to compare the survival between groups. Cox regression was used to analyze the independent prognostic factors of rectal cancer.
RESULTSThe patients in each stage were stage 0 with 18 cases, stage I with 209 cases, stage II with 235 cases, and stage III with 394 cases. All patients received curative surgery. There were 296 patients evaluated as cT3, cT4 and any T with N+ received preoperative radiotherapy. 5.4% patients got pathological complete response (16/296), and the recurrence rate was 4.7% (14/296). After a median time of 41.7 months (range 4.1 to 144.0 months) follow-up, the 5-year overall survival rate in stage 0 to I of was 91.0%, stage II 86.2%, and stage III 60.0%, with a significant difference (P=0.000). The cumulative local recurrence rate was 4.8% (41/856), of which 70.7% (29/41) occurred within 3 years postoperatively, 97.6% (40/41) in 5 years. The cumulative distant metastasis rate was 16.4% (140/856), of which 82.9% (129/140) occurred within 3 years postoperatively, 96.4% (135/140) in 5 years. The incidence of abnormal imaging findings was significantly higher in pulmonary than liver and other sites metastases (75.0% vs. 21.7%, χ² =25.691, P=0.000). The incidence of CEA elevation was significantly higher in liver than lung and other sites metastases (56.8% vs. 37.8%, χ² =25.691, P=0.000). Multivariable analysis showed that age (P=0.015, HR=1.385, 95% CI: 1.066 to 1.801), surgical approach (P=0.029, HR=1.337, 95% CI: 1.030 to 1.733), differentiation (P=0.000, HR=1.535, 95% CI: 1.222 to 1.928), TNM stage (P=0.000, HR=1.349, 95% CI: 1.260 to 1.444) and lymphovascular invasion (P=0.001, HR=1.715, 95% CI: 1.258 to 2.342) are the independent prognostic factors for rectal cancer.
CONCLUSIONSAge, surgical approach, differentiation, TNM stage and lymphovascular invasion are independent prognostic factors for rectal cancer. Preoperative evaluation and combined modality therapy can significant reduce the local recurrence and improve overall survival for rectal cancer patients.
Aged ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Rectal Neoplasms ; diagnosis ; surgery ; therapy ; Retrospective Studies ; Survival Rate
9.Clinical characteristics and prognosis of colon cancer patient with extremely elevated carcinoembryonic antigen level.
Pengju CHEN ; Yunfeng YAO ; Dakui ZHANG ; Jin GU
Chinese Journal of Gastrointestinal Surgery 2015;18(10):1026-1031
OBJECTIVETo explore the clinicopathological characteristics and prognosis of colon cancer patients with extremely elevated serum carcinoembryonic antigen(CEA) level before operation(>50 μg/L).
METHODSClinicopathological and follow-up data of 1250 patients with colonic adenocarcinoma undergoing primary tumor resection between January 2001 and December 2011 were retrospectively analyzed. All the patients were divided into three groups according to the preoperative serum CEA levels as normal group (0-5 μg/L, 721 cases), elevated group(5-50 μg/L, 408 cases) and extremely elevated(>50 μg/L, 121 cases). Kaplan-Meier method was used to analyze the overall survival and disease-free survival. Log-rank test was used to compare the survival between groups. Cox regression was used to screen the independent prognostic factors of colon cancer.
RESULTSCompared with normal and elevated groups, patients with extremely elevated CEA had more advanced T,N,M stages (P<0.01), more palliative surgery (P<0.01) and more lymphovascular invasion(P<0.01). During the follow-up, patients with extremely elevated CEA demonstrated significantly higher ratio of distant metastases and liver metastases (both P=0.001). After radical surgery, 5-year overall survival rate of patients with normal, elevated and extremely elevated CEA levels was 70.1%, 54.4% and 42%, respectively, with statistically significant difference among three groups (P<0.001). Multivariate analysis showed that tumor differentiation, TNM staging, preoperative CEA levels, lymphovascular invasion and adjuvant chemotherapy were independent prognostic factors for colon cancer (all P<0.01).
CONCLUSIONSColon cancer patients with extremely elevated preoperative CEA levels are associated with more unfavorable pathological factors, advanced TNM stage and more distant metastases (especially the liver metastases) during the follow-up. The elevated degree of preoperative CEA level is an independent poor prognostic factor of patients with colon cancer.
10.Clinical characteristics and prognosis of colon cancer patient with extremely elevated carcinoembryonic antigen level
Pengju CHEN ; Yunfeng YAO ; Dakui ZHANG ; Jin GU
Chinese Journal of Gastrointestinal Surgery 2015;(10):1026-1031
Objective To explore the clinicopathological characteristics and prognosis of colon cancer patients with extremely elevated serum carcinoembryonic antigen ﹙CEA) level before operation﹙>50 μg/L). Methods Clinicopathological and follow-up data of 1250 patients with colonic adenocarcinoma undergoing primary tumor resection between January 2001 and December 2011 were retrospectively analyzed. All the patients were divided into three groups according to the preoperative serum CEA levels as normal group ﹙0-5 μg/L, 721 cases), elevated group ﹙5-50 μg/L, 408 cases) and extremely elevated ﹙>50 μg/L, 121 cases). Kaplan-Meier method was used to analyze the overall survival and disease-free survival. Log-rank test was used to compare the survival between groups. Cox regression was used to screen the independent prognostic factors of colon cancer. Results Compared with normal and elevated groups, patients with extremely elevated CEA had more advanced T,N,M stages ﹙P<0.01), more palliative surgery ﹙P<0.01) and more lymphovascular invasion﹙P<0.01). During the follow-up, patients with extremely elevated CEA demonstrated significantly higher ratio of distant metastases and liver metastases ﹙both P=0.001). After radical surgery, 5-year overall survival rate of patients with normal, elevated and extremely elevated CEA levels was 70.1%, 54.4% and 42%, respectively, with statistically significant difference among three groups ﹙P<0.001). Multivariate analysis showed that tumor differentiation, TNM staging, preoperative CEA levels, lymphovascular invasion and adjuvant chemotherapy were independent prognostic factors for colon cancer ﹙all P<0.01). Conclusions Colon cancer patients with extremely elevated preoperative CEA levels are associated with more unfavorable pathological factors, advanced TNM stage and more distant metastases﹙especially the liver metastases) during the follow-up. The elevated degree of preoperative CEA level is an independent poor prognostic factor of patients with colon cancer.

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