Significance of urinaryN 1,N 8-diacetylspermidine andN 1,N 12-diacetylspermine as indicators of neoplastic diseases

N ¹,N ⁸-Diacetylspermidine (Ac₂Spd) andN ¹,N ¹² diacetylspermine (Ac₂Spm), the occurrence of which in healthy human urine was demonstrated recently, increased much more frequently and markedly than total polyamines, acetylputrescine,N ¹-acetylspermidine andN ⁸-acetylspermidine in patients with urogenital malignancies. Ac₂Spd was hardly elevated in cases of benign disease, while Ac₂Spm only infrequently stayed within normal limits in patients with malignant disorders. Urine samples from more than 90% of healthy persons, but fewer than 10% of patients with malignancies, gave values within normal limits for both Ac₂Spd and Ac₂Spm. Simultaneous reference to these diacetylpolyamines is therefore useful in distinguishing patients with malignancies from healthy persons.     

Diagnostic role and prognostic value of tumor markers in high-grade gastro-enteropancreatic neuroendocrine neoplasms

ObjectivesHigh-grade gastro-enteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of rare tumors of two different types: well differentiated neuroendocrine tumors grade 3 (NETs G3) and poorly differentiated neuroendocrine carcinomas (NECs). This study aimed to explore the value of eight common preoperative markers in differentiating NETs G3 from NECs and the prognosis prediction of high-grade GEP-NENs.MethodsSeventy-two patients diagnosed with high-grade GEP-NENs who underwent surgery at our institution were recruited for this study. Demographic and clinicopathological characteristics, preoperative serum tumor markers, and survival data were collected and analyzed. Kaplan–Meier methods were used to analyze survival rates, and a Cox regression model was used to perform multivariate analyses.ResultsSerum carcinoembryonic antigen (CEA) was dramatically higher in NECs than in NETs G3 (P = 0.025). After follow-up, 57 of the 72 patients remained for survival analysis. Elevated serum carbohydrate antigen 19-9 (CA19-9), CEA, cancer antigen 125 and sialic acid (SA) levels indicated poorer survival of high-grade GEP-NEN patients. Only CA19-9 (HR: 6.901, 95% CI: 1.843 to 25.837, P = 0.004) was regarded as an independent risk factor for overall survival. Serum CA19-9 (HR: 4.689, 95% CI: 1.127 to 19.506, P = 0.034) was also regarded as an independent factor for overall survival in NECs.ConclusionsSerum CEA levels can be used to distinguish NETs G3 from NECs. Preoperative CA19-9, CEA, cancer antigen 125 and SA levels have predictive value in the prognosis of high-grade GEP-NENs. Preoperative CA19-9, neuron-specific enolase, and SA levels can predict the prognosis of NECs.     

Increase of N 1 ,N 12-diacetylspermine in tissues from colorectal cancer and its liver metastasis

Purpose

N ¹ ,N ¹²-Diacetylspermine (DiAcSpm) is a tumor marker featured by increase in the urine of patients with cancers, including early colorectal cancer, but where and how DiAcSpm is made remains unclear. We aimed to clarify whether colorectal cancer tissues produce increased amounts of DiAcSpm, and if they do, to examine whether tissue DiAcSpm level may serve as a criterion of tissue malignancy.

Methods

Tissue samples were obtained from 140 patients (13 low-grade intraepithelial neoplasia, 98 high-grade intraepithelial neoplasia and 29 colorectal cancer) treated for colorectal cancer and intraepithelial neoplasia at Tokyo Metropolitan Komagome Hospital between November 2007 and April 2011. The DiAcSpm level in cancer and adjacent normal tissue extracts was compared, and its relationship with clinical stages of the diseases was analyzed.

Results

DiAcSpm levels were higher in colorectal cancer tissue (p < 0.01, n = 12) and its liver metastasis (p < 0.05, n = 5) than in adjacent normal tissues. The tumor/normal ratio of tissue DiAcSpm content was examined for endoscopically obtained tumor and adjacent normal tissues from patients with intraepithelial neoplasia. The ratio was greater than 1.5 in 38 % (5/13) and 78 % (84/108) of low-grade intraepithelial neoplasia and high-grade intraepithelial neoplasia, respectively.

Conclusions

Tissue DiAcSpm levels increase in the tissue of colorectal cancer and also in precancerous lesion, such as high-grade intraepithelial neoplasia. The increase is considered a sign that a tissue is acquiring malignant characteristics. It is likely that the DiAcSpm produced by cancer cells is responsible for the frequent increase in urinary DiAcSpm in early cancer patients.     

Diagnostic accuracy of urine filtration and dipstick tests for Schistosoma haematobium infection in a lightly infected population of Ghanaian schoolchildren

Two screening methods, reagent dipsticks for hematuria and urine filtration for Schistosoma haematobium eggs, were evaluated for their sensitivity and specificity in diagnosing infection with S. haematobium in lightly infected Ghanaian children. Schoolchildren aged 8–18 years (n = 255) provided urine samples on three occasions. Overall, 36.4% of girls and 50.7% of boys presented with eggs at least once; 3.3% of girls and 7.5% of boys presented with both eggs and hematuria three times. Many children presented with eggs but without hematuria, or with hematuria but without eggs. When each child was screened three times, the sensitivity of each test method improved by at least 22.9% as compared with single screening, but previously unidentified infections were detected at the third screening, indicating that even three screenings is insufficient. Nearly half of lightly infected children (<50 eggs/10 ml urine, by maximum egg count) were egg-positive during only one of three screenings. Thus, data presented here indicate that when individuals are screened repeatedly, infection status can be assessed more accurately, control programs can be properly evaluated, and population estimates of S. haematobium infection may be made with increased confidence, as compared with single screening.     

肿瘤标记物在细胞学阴性的恶性腹水中的诊断价值

目的 探讨肿瘤标志物CEA 、CA199、CA125在细胞学阴性的恶性腹水中的诊断价值.方法 检测189例腹水患者的血清和腹水肿瘤标记物,评估肿瘤标记物在细胞学阴性的恶性腹水中的诊断价值.结果 在预设的临界值,细胞学阴性的恶性腹水患者血清和腹水CEA 、CA19-9阳性率明显高于良性腹水组（P ＜0.05）;CA12-5两组比较,差异无统计学意义（P＞0.05）.血清CEA 、CA19-9诊断敏感性较低;腹水CEA 、CA19-9诊断敏感性明显提高,特异性相当.腹水CEA、CA19-9的ROC曲线下面积分别为0.94、0.88.结论 肿瘤标记物CEA、CA19-9有助于细胞学阴性恶性腹水的鉴别诊断,CA12-5无诊断价值;其中腹水CEA诊断价值较高.     

Adjusting CA19-9 values to predict malignancy in obstructive jaundice: influence of bilirubin and C-reactive protein

AIM: To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice (BJ) and malignant jaundice (MJ).METHODS: All patients admitted for obstructive jaundice, in the period 2005-2009, were prospectively enrolled in the study, obtaining a total of 102 patients. On admission, all patients underwent complete standard blood test examinations including C-reactive protein (CRP), bilirubin, CA19-9. Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels (total bilirubin > 2.0 mg/dL). The standard cut-off level for CA19-9 was 32 U/mL, whereas for CRP this was 1.5 mg/L. The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value. The patients were divided into 2 groups, MJ and BJ, and after the adjustment a comparison between the 2 groups of patients was performed. Sensitivity, specificity and positive predictive values were calculated before and after the adjustment.RESULTS: Of the 102 patients, 51 were affected by BJ and 51 by MJ. Pathologic CA19-9 levels were found in 71.7% of the patients. In the group of 51 BJ patients there were 29 (56.9%) males and 22 (43.1%) females with a median age of 66 years (range 24-96 years), whereas in the MJ group there were 24 (47%) males and 27 (53%) females, with a mean age of 70 years (range 30-92 years). Pathologic CA19-9 serum level was found in 82.3% of MJ. CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ. Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ (P = 0.000 and P = 0.02), while the CRP level was significantly higher in BJ (P = 0.000). Considering a CA19-9 cut-off level of 32 U/mL, 82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9 (P = 0.002). A CA19-9 cut-off of 100 U/mL increases the difference between the two groups: 35.3% in BJ and 68.6% in MJ (P = 0.0007). Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value (P = 0.003), while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value (P = 0.000004). Sensitivity, specificity, positive predictive values of CA19-9 > 32 U/mL were 82.3%, 45% and 59.1%; when the cut-off was CA19-9 > 100 U/mL they were, respectively, 68.6%, 64.7% and 66%. When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values, these became 49%, 78.4%, 69.4% and 76.5%, 68.6%, 70.9%, respectively.CONCLUSION: The present study proposes CRP as a new and useful correction factor to improve the diagnostic value of the CA19-9 tumor marker in patients with cholestatic jaundice.     

Serum chemokine levels as prognostic markers in patients with early systemic sclerosis: a multicenter, prospective, observational study

Objective

To assess the utility of serum chemokine levels as a prognostic indicator of disease progression in systemic sclerosis (SSc) patients with early onset disease.

Methods

Seventy Japanese patients with early onset SSc presenting with diffuse skin sclerosis and/or interstitial lung disease were registered in a multicenter, observational study. Concentrations of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in serum samples from all patients were measured using cytometric beads array. In 33 patients, chemokine levels were measured each year for 4 years. The ability of baseline chemokine levels to predict changes in clinical features were evaluated statistically by multiple regression analysis.

Results

At their first visit, serum levels of CCL2, CCL5, CXCL8, CXCL9, and CXCL10 were significantly elevated in patients with SSc compared with healthy controls. There were significant associations between CCL2 and CXCL8 levels and between CXCL9 and CXCL10 levels in patients. The initial serum CXCL8 levels were significantly associated with the HAQ-DI at the fourth year while the %VC of baseline tended to be negatively associated with HAQ-DI at the fourth year. Initial chemokine levels were not associated with other clinical features including skin thickness score and the respiratory function.

Conclusion

Serum CXCL8 level may serve as a prognostic indicator of the physical dysfunction in SSc. Further longitudinal studies of larger populations are needed to confirm these findings.     

A novel role of serum cytochrome c as a tumor marker in patients with operable cancer

Purpose  This study aimed to evaluate serum cytochrome c (cyto-c) levels as a novel role of tumor marker in patients with operable malignant tumors. Methods  Serum cyto-c levels and lactate dehydrogenase (LD) activity were measured in a total of 257 cases (232 malignant and 25 benign). To identify the relationship between serum cyto-c and current tumor markers, six variables, such as gender, age, invasion, lymph node metastasis, distant metastasis, and LD, were analyzed by uni- and multivariate regression analysis methods. The test performance of serum cyto-c for the prediction of malignant behavior was evaluated by receiver operating characteristic (ROC) curves. Results  The serum cyto-c level was significantly higher in patients with malignant tumors than patients with benign tumors (20.6 vs. 15.5 ng/mL; P = 0.017, Mann–Whitney U test). No difference in the levels among subtypes of cancer was found, indicating that the change in serum cyto-c levels reflect cancer individually and not specific subtypes of cancer. The survival in patients with serum cyto-c levels over 40 ng/mL was poor (Kaplan–Meier test, P < 0.0001, Hazard ratio 16.76, 95% confidential interval 4.45–63.04). Multiple linear regression analyses disclosed the close association of serum cyto-c levels with invasion (P = 0.0004), metastasis (P = 0.0262) except for regional lymph node metastasis, and activity of serum LD (P < 0.0001), all of which are well known to represent malignant behavior. Conversely, the measurement of serum cyto-c was verified to have excellent diagnostic accuracy of 0.802 and 0.781 for the detection of invasion and metastasis (the area under curves of the constructed ROCs). Conclusion  Serum cyto-c is a potent tumor marker as a predictor for malignant potential in cancers.     

Cell surface expression of lysosome-associated membrane protein-2 (lamp2) and CD63 as markers of in vivo platelet activation in malignancy

Abstract: Platelets may become activated in vivo in a number of prethrombotic conditions including cancer. In the present study, cell surface expression of lysosome-associated membrane protein-2 (lamp2) and CD63 (lamp3) were examined by flow cytometry in 15 healthy volunteers and 5 patients with metastatic cancer to determine their utility as markers of in vivo platelet activation. Unstimulated platelets from controls had low levels of lamp2 expression, in contrast to cancer patients, who had significantly elevated levels (3.79 ± 1.48% vs 33.9 ± 5.6%). Upon stimulation with collagen, a greater than two-fold increase in the number of platelets expressing detectable levels of lamp2 was seen only among controls and not in cancer patients. Stimulation with collagen also resulted in a nearly two-fold increase in the proportion of platelets expressing CD63 in the control group, and a less than 1.5-fold increase in CD63 was seen in the patient group. The results suggest that cell surface lamp2 and CD63, like cell surface expression of GMP-140, may be good indicators of in vivo platelet activation and may be potentially useful in identifying patients with prethrombotic disorders.     

Diagnostic and prognostic value of urine NT-proBNP levels in heart failure patients

BACKGROUND: Plasma NT-proBNP levels are sensitive markers of ventricular dysfunction. However, studies of natriuretic peptides in urine are limited. AIMS: To compare urine and plasma NT-proBNP levels and to investigate the diagnostic and prognostic value of urine levels in heart failure (HF). METHODS: Urinary and plasma NT-proBNP levels were measured in 96 HF patients and 20 control subjects. The patients were functionally classified according to the NYHA criteria. RESULTS: Urine NT-proBNP was higher in HF patients than in control subjects (94+/-31 pg/ml vs. 67+/-6 pg/ml, p<0.0001), correlating with plasma NT-proBNP levels (r=0.78, p<0.0001). Urinary levels were elevated in the more severe functional classes and diminished in obese patients. Urine NT-proBNP was a good tool for diagnosis of HF, the area under the curve (AUC) being 0.96+/-0.02 (p<0.0001), and for predicting 12-month cardiac events (p=0.011). To determine the prognostic power of urinary NT-proBNP in detecting 12-month cardiac mortality, we obtained an AUC of 0.75+/-0.10 (p=0.015). CONCLUSION: Urinary NT-proBNP, a relatively simple non-invasive test, is a new candidate marker for the diagnosis and evaluation of prognosis in HF and for the characterization of functional status in these patients.     

Evaluation of Apaf-1 and procaspases-2, -3, -7, -8, and -9 as potential prognostic markers in acute leukemia

Recent studies have suggested that variations in levels of caspases, a family of intracellular cysteine proteases, can profoundly affect the ability of cells to undergo apoptosis. In this study, immunoblotting was used to examine levels of apoptotic protease activating factor-1 (Apaf-1) and procaspases-2, -3, -7, -8, and -9 in bone marrow samples (at least 80% leukemia) harvested before chemotherapy from adults with newly diagnosed acute myelogenous leukemia (AML, 42 patients) and acute lymphocytic leukemia (ALL, 18 patients). Levels of each of these polypeptides varied over a more than 10-fold range between specimens. In AML samples, expression of procaspase-2 correlated with levels of Apaf-1 (R(s) = 0.52, P <.02), procaspase-3 (R(s) = 0.56, P <.006) and procaspase-8 (R(s) = 0.64, P <.002). In ALL samples, expression of procaspases-7 and -9 was highly correlated (R(s) = 0.90, P <.003). Levels of these polypeptides did not correlate with prognostic factors or response to induction chemotherapy. In further studies, 16 paired samples (13 AML, 3 ALL), the first harvested before induction therapy and the second harvested at the time of leukemia regrowth, were also examined. There were no systematic alterations in levels of Apaf-1 or procaspases at relapse compared with diagnosis. These results indicate that levels of initiator caspases vary widely among different leukemia specimens but cast doubt on the hypothesis that this variation is a major determinant of drug sensitivity for acute leukemia in the clinical setting. (Blood. 2000;96:3922-3931)     

血清CEA、NSE、CYFRA21-1水平与肺癌近期疗效的相关性研究

目的 评价癌胚抗原（CEA）、细胞角蛋白19片段（CYFRA21-1）、神经元特异性烯醇化酶（NSE）三项肿瘤标志物在肺癌化疗前后的表达意义.方法 97例确诊肺癌患者化疗前后,常规检查血清CEA、NSE和CYFRA21-1水平,评估变化.结果 三种病理类型肺癌化疗后,疗效评价有效者,腺癌患者CEA显著下降（P〈0.05）,小细胞癌患者NSE显著下降（P〈0.05）,而疗效评价稳定或恶化者,化疗前后其值无明显变化或升高.结论 三项肿瘤标志物水平对肺癌化疗疗效有一定判断价值.     

Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors

Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.     

The value of combined use of survivin, cytokeratin 20 and mucin 7 mRNA for bladder cancer detection in voided urine

Objectives To evaluate the value of combined use of survivin, cytokeratin (CK) 20 and mucin (MUC) 7 mRNA in comparison with voided urine cytology in the detection of bladder cancer patients. Methods One hundred and fifty three patients and 20 healthy volunteers were evaluated by RT-PCR for detecting survivin, CK-20 and MUC7 mRNA in voided urine before cystoscopy. The three markers and cytology were evaluated independently or in combinations. Results The overall sensitivity and specificity were 90.4 and 94.7% for survivin, 82.6 and 97.4% for CK-20, 62.6 and 94.7% for MUC7 and 46.0 and 100% for voided urine cytology. Combined sensitivity of voided urine cytology with the three biomarkers together was higher than either combined sensitivity of voided urine cytology with one of the biomarkers or than that of the biomarker alone. Conclusions Combined use of the three markers can improve the sensitivity for detecting bladder cancer.     

Expression of MMP-9 and TIMP-1 as prognostic markers in gastric carcinoma

BACKGROUND/AIMS: The aim of the present work is to clarify the role of metalloproteinase-9 and its inhibitor in the evolution of gastric cancer after surgical resection. METHODOLOGY: We have studied 44 gastric cancer patients submitted to surgery. There were 13 proximal tumors, 16 located in the middle third and 15 in the distal one. Overall survival was 26% at 6 years. Metalloproteinase-9 and tissue inhibitor of metalloproteinase concentrations were investigated by means of ELISA in frozen samples of tumoral and normal gastric mucosa. RESULTS: Mean concentration of metalloproteinase-9 in tumoral tissue was 42 ng/mg of total protein, and this value was 6.9 times greater than the mean concentration in non-tumoral tissue. Cancer tissue also expressed higher levels of TIMP-1, 7.25 versus 4.39 ng/mg of protein. Higher levels of metalloproteinase expression in tumoral tissue, greater [metalloproteinase in tumor]/[metalloproteinase in non-tumor] ratio and greater [metalloproteinase]/[inhibitor] ratio in tumor cells, were all of them statistically related to a worse prognosis when T1 and T2 tumors were considered. CONCLUSIONS: The expression of metalloproteinase-9 or its inhibitor is related to a more aggressive phenotype of gastric cancer.     

Diagnostic and therapeutic approach to persistent or recurrent fevers of unknown origin in adult stem cell transplantation and haematological malignancy

Persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients on broad-spectrum antibiotics have traditionally been treated with empirical antifungal therapy (EAFT). The lack of survival benefit seen with the use of amphotericin B deoxycholate (AmB-D) as EAFT has been attributed to its toxicities. More recently, newer, less toxic and more expensive antifungal agents such as the lipid formulations of AmB, the newer azoles (fluconazole, itraconazole and voriconazole) and caspofungin have been analysed in a number of EAFT trials. Compared with AmB-D the newer agents have superior safety but are of equivalent efficacy. This lack of survival advantage is related to the fact that the trigger for commencement of EAFT is late and non-specific. Thus, alternative approaches are required. New sensitive serological and molecular tests for the detection of Aspergillus antigens and genomic DNA have been developed and evaluated in accuracy studies. These tests have been incorporated into management strategies (i.e. pre-emptive strategies) to direct antifungal therapy. The pre-emptive approach has been shown to be safe and feasible but its impact on clinically important patient outcomes such as survival is less clear. Other advances include the introduction of effective, non-toxic mould-active antifungal prophylaxis and patient risk-group stratification. In this paper we provide new evidence-based algorithms for the diagnosis and treatment of PFUO in adult patients undergoing stem cell transplantation and chemotherapy for haematological malignancy which incorporate these newer diagnostic tests and are directed by the risk category of the patient and type of antifungal prophylaxis the patient is receiving.     

Diagnostic and prognostic value of some biochemical markers in early knee osteoarthritis

BackgroundOsteoarthritis (OA); the most common joint disease, is not only characterized by cartilage destruction; but also by alteration of bone and synovial tissue metabolism, though their relative importance in the initiation and progression of OA is still debated. To identify patients with a high risk for destructive OA, more sensitive techniques than plain X-rays are needed.Aim of the workTo study the diagnostic and prognostic value of some biochemical markers serum hyaluronic acid (HA) and serum cartilage oligomeric matrix protein (COMP), high sensitive C-reactive protein (hs-CRP) in the included patients had early OA knees and their relation to disease progression.Patients and methodsSixty patients had early knee OA and 20 control subjects were included. WOMAC index, laboratory investigations (COMP, HA, hs-CRP) and radiological evaluation (Kellgren and Lawrence grading scale and Thomas compartmental score) were performed for each patient at baseline and after one year.ResultsHA was significantly higher in patients than controls (p > 0.001) with the highest specificity and positive predictive value. It was significantly correlated with COMP at baseline and after one year (p = 0.01). The levels of HA at baseline correlated with its levels after one year (p > 0.001). It also correlated with K–L grading score (p = 0.02). COMP was significantly higher in patients than controls (p > 0.001). It was significantly correlated with Thomas score after one year (p = 0.007). Baseline levels of COMP correlated significantly with its levels after one year (p = 0.005). The differences of the serum levels of hs-CRP at the baseline evaluation and after one year between patients and controls were not statistically significant (p = 0.4, 0.5, respectively).ConclusionsThe measurements of HA and COMP may be of diagnostic and prognostic value in differentiating patients with early joint destruction and in determining disease progression. A single biochemical marker has definitive diagnostic value and the combination with other biochemical markers as well as with clinical and radiographic data would most likely help to improve the clinical assessment of patients. Serum hs-CRP is not a good predictor of individual patient progression and has a poor sensitivity and specificity.     

肺癌患者血清肿瘤标志物水平变化与化疗疗效及生存时间的相关性

目的探讨晚期肺癌患者化疗前后血清癌胚抗原（CEA）、细胞角质蛋白（CYFRA21-1）、鳞状细胞癌抗原（SCC）和神经烯醇化酶（NSE）水平变化与化疗疗效及生存时间的相关性。方法分别采集2006年1月至2012年6月确诊肺癌（Ⅲb-Ⅳ期）116例患者的化疗前及四疗程化疗后的血清标本,检测每份标本CEA、CYFRA21-1、SCC和NSE四种肿瘤标记物水平,探讨它们之间的差值差异及与化疗效果和生存时间的关系。结果四疗程化疗有效及进展的患者中位生存时间为16个月及9个月;结合生存曲线显示化疗有效的晚期肺癌患者较进展者生存时间更长。化疗前后肿瘤标志物水平变化与化疗疗效密切相关。化疗有效者相应肿瘤标志物下降;进展者标志物上升。其中不同疗效组的鳞癌患者CYFRA21-1及SCC水平,腺癌患者CEA水平,小细胞癌患者CEA及NSE差值差异明显（P〈0．05）。通过比较不同生存时间组的患者化疗前后肿瘤标志物的差值差异发现患者生存时间越长,化疗后相应的肿瘤标志物下降幅度越大;生存时间越短标志物上升越明显。其中鳞癌患者CYFRA21—1及SCC,腺癌患者CEA和小细胞癌患者CEA及NSE指标变化有统计学意义。结论CEA、CYFRA21—1,SCC和NSE这四种肿瘤标志物化疗前后差值可作为反映化疗疗效及评估一年生存时间的重要指标,且具有病理类型的特异性。