C4.4A as a biomarker in pulmonary adenocarcinoma and squamous cell carcinoma

The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uPAR family of membrane proteins, qualifies as such a potential informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression to invasive carcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A in squamous epithelium. In pulmonary adenocarcinomas, a fraction of cases is positive for C4.4A, which is surprising, given the origin of these carcinomas from mucin-producing and not squamous epithelium. Interestingly, this correlates with a highly compromised patient survival and a predominant solid tumor growth pattern. Circumstantial evidence suggests an inverse relationship between C4.4A and the tumor suppressor LKB1. This might provide a link to the prognostic impact of C4.4A in patients with adenocarcinomas of the lung and could potentially be exploited for predicting the efficacy of treatment targeting components of the LKB1 pathway.     

Prognostic and therapeutic significance of the flow cytometric nuclear DNA content in non-small cell lung cancer

To evaluate prognostic and therapeutic significance, tumor DNA content was determined by flow cytometry in 310 paraffin-embedded tissue samples obtained surgically from 130 patients with non-small cell lung cancer. Ninety-six (76.8%) patients had DNA aneuploid patterns that were statistically higher in adenocarcinoma than in squamous cell carcinoma. A better 5-year survival rate was observed in Group A (DNA diploidy, 69.6%) than in Group B (DNA aneuploidy and DNA peridiploidy, 33.2%; P less than 0.001). The survival curves of the patients in Group B continued to decrease during the next 2.5 years. Cox's model analysis showed that both the pathologic stage and the DNA content were the significant prognostic factors for survival. However, the DNA content was an independent prognostic factor in squamous cell carcinoma, but not in adenocarcinoma. These results indicate that DNA content analysis is useful for the evaluation of clinical behavior and prognosis, and that the clinical value of the DNA content must be differentiated between squamous cell carcinoma and adenocarcinoma.     

P2RY6在非小细胞肺癌中的表达和临床意义分析

  目的  探讨P2RY6在非小细胞肺癌（non-small cell lung cancer,NSCLC）患者中的表达及临床意义。  方法  在基因表达集（Gene Expression Omnibus,GEO）和癌症基因组图谱计划（The Cancer Genome Atlas Program,TCGA）数据库中获取多个NSCLC、肺腺癌和肺鳞癌的基因表达以及临床信息数据集。使用非参数检验分析癌组织与邻近正常组织的P2RY6表达水平差异,并且通过免疫组织化学研究肺鳞癌及肺腺癌组织和正常组织的P2RY6蛋白表达情况。使用χ2检验分析P2RY6表达与肺腺癌、肺鳞癌患者临床特征之间的相关性。使用Kaplan-Meier方法和Log-rank检验评估肺腺癌和肺鳞癌P2RY6表达水平与总生存期和无进展生存期之间的关系。使用Cox比例风险回归模型进一步评估P2RY6表达量对肺鳞癌患者总生存期和无进展生存期的预测效能。  结果  P2RY6在NSCLC、肺腺癌和肺鳞癌中均高表达。在肺腺癌患者中,P2RY6表达与生存无关,而与性别有关。在P2RY6高表达的肺鳞癌患者中,总生存期和无进展生存期较短,P2RY6高表达是独立危险因素。  结论  P2RY6与肺鳞癌患者的生存相关,P2RY6高表达预示着肺鳞癌患者总生存期与无进展生存期较短,是预后不良的独立危险因素。      

肺腺癌和鳞癌中VEGF-C和新生淋巴管表达的预后价值

背景与目的血管内皮生长因子-C(vascu larendothelial growth factor-C,VEGF-C)是VEGF家族的成员之一,且已被证明是相对特异的血管内皮生成因子,其与受体VEGFR-3结合后可激活淋巴管的生成,为肿瘤的淋巴结转移创造有利的条件。本研究旨在探讨VEGF-C和新生淋巴管在肺腺癌和鳞癌中的表达特点及其预后意义。方法以跨粘膜样受体蛋白(podoplanin)标记新生淋巴管内皮细胞,采用免疫组化方法检测98例IIIa(N2)期肺腺癌和鳞癌中VEGF-C和新生淋巴管的表达。结果 VEGF-C的表达率与微淋巴管密度(lymphatic microvessel density,LMVD)之间存在正相关(r=0.783,P<0.01)。VEGF-C高表达组的LMVD大于低表达组(P<0.01)。肺腺癌VEGF-C和新生淋巴管表达率明显高于肺鳞癌(P<0.01)。VEGF-C阳性表达患者的生存率明显低于阴性患者(P<0.05),VEGF-C是影响预后的独立因素。结论 IIIa(N2)期肺腺癌新生淋巴管的表达较鳞癌明显。VEGF-C是影响IIIa(N2)期肺腺癌和鳞癌患者预后的独立因素。     

Proteins involved in DNA damage response pathways and survival of stage I non-small-cell lung cancer patients

BackgroundBiological complexity leads to significant variation in the survival of patients with stage I non-small-cell lung cancer (NSCLC). DNA damage response (DDR) pathways play a critical role in maintaining genomic stability and in the progression of NSCLC. Therefore, the development of a prognostic biomarker focusing on DDR pathways is an intriguing issue.Patients and methodsExpression of several proteins (ATM, ATMpS1981, γH2AX, 53BP1, 53BP1pS25, Chk2, Chk2pT68, MDC1, MDC1pS964, BRCA1pS1423, and ERCC1) and overall survival were investigated in 889 pathological stage I NSCLC patients.ResultsLow expression of BRCA1pS1423 or ERCC1 was significantly associated with worse survival in the whole cohort of patients. Analysis performed based on histology revealed that low expression of γH2AX, Chk2pT68, or ERCC1 was a poor prognostic factor in squamous cell carcinoma patients [adjusted hazard ratio (aHR), Cox P: 1.544, 0.012 for γH2AX; 1.624, 0.010 for Chk2pT68; 1.569, 0.011 for ERCC1]. The analysis of the interaction between two proteins showed that this effect was more pronounced in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients.ConclusionsThe proteins involved in DDR pathways exhibited differential expression between squamous cell carcinoma and adenocarcinoma and were important determinants of survival in stage I squamous cell carcinoma patients.     

Tumour cell expression of C4.4A, a structural homologue of the urokinase receptor, correlates with poor prognosis in non-small cell lung cancer

PURPOSE: C4.4A expression has been implicated in human cancer progression. This protein is a structural homologue of the urokinase receptor, uPAR, which constitutes a well-established prognostic marker in various human cancers. Nonetheless, little is known about the prognostic significance of C4.4A expression. In the present study, we therefore explored the possible association between C4.4A expression and prognosis in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Tissue sections from 108 NSCLC patients were subjected to immunohistochemical staining using a polyclonal antibody that specifically recognises human C4.4A. Staining frequency and intensity was scored semiquantitatively and grouped into cancers with high and low expression of C4.4A. Kaplan-Meier survival curves were generated to evaluate the significance of C4.4A expression in prognosis of NSCLC patients. RESULTS: High C4.4A expression was observed in 42% of the NSCLC specimens analysed, and this correlates with overall survival (p = 0.012). A remarkably strong correlation was noted between high expression of C4.4A in pulmonary adenocarcinoma and survival (p < 0.0001). Multivariate Cox regression analysis shows that high C4.4A expression is an independent predictor of poor disease outcome in NSCLC (risk ratio, 1.42; 95% confidence interval, 1.09-1.86; p = 0.009). Although histological type is not a predictor of outcome in NSCLC, high C4.4A expression in adenocarcinoma is nevertheless a very strong predictor of poor disease outcome (risk ratio, 1.62; 95% confidence interval, 1.24-2.09; p = 0.001). CONCLUSIONS: High tumour cell C4.4A expression is associated with shorter survival for NSCLC patients. Patients with pulmonary adenocarcinoma have a particularly poor prognosis if this histological type is combined with high tumour cell C4.4A expression.     

Histological classification of lung cancer

A histological classification should provide guidelines for tumor diagnosis in order to evaluate patient prognosis and therapy. Pre-invasive lesions identified as precursors of invasive lung carcinoma are: squamous dysplasia/carcinoma in situ, atypical adenomatous hyperplasia and idiopatic pulmonary neuroendocrine cell hyperplasia. Squamous carcinoma and adenocarcinoma are the commonest types of lung carcinoma with the latter increasing in many countries mainly for changed smoking habits. Bronchioloalveolar carcinomas include exclusively noninvasive mucinous or non-mucinous tumors. Neuroendocrine tumors range from well differentiated neuroendocrine carcinoma (typical carcinoid) to intermediate grade (atypical carcinoma) to very aggressive poorly differentiated lesions (large cell neuroendocrine carcinoma and small cell carcinoma).     

ANGPT1基因在肺腺癌组织中的表达及其预后价值分析

目的:探索血管生成素1（angiopoietin 1,ANGPT1)在肺腺癌组织中的表达及预后意义。方法:从癌症基因组图谱(TCGA)数据库收集肺腺癌和肺鳞癌数据,并下载ANGPT1基因表达谱资料及临床信息资料。采用t检验明确ANGPT1在肺癌组织和正常组织中的表达差异,χ2检验分析ANGPT1基因表达与肺腺癌患者临床病理特征的相关性,Log-rank检验进行生存分析;利用基因集富集分析（Gene Set Enrichment Analysis,GSEA）方法,预测肺腺癌中可能受ANGPT1调控的相关通路。结果:ANGPT1基因在肺癌组织中低表达;其表达水平与T分期（P=0.013)呈负相关;ANGPT1低表达的肺腺癌患者预后明显差于高表达患者（P=0.006）,是影响肺腺癌预后的独立保护因素(P＜0.05)。GSEA结果显示,ANGPT1可能通过调节G2M检查点、DNA损伤修复、凋亡、mTOR信号、MYC信号、有丝分裂纺锤体等细胞增殖相关通路影响肺腺癌的发生发展。结论:ANGPT1是肺腺癌的独立预后保护因素,可能成为肺腺癌的潜在预后标志物和治疗靶点。     

ECT2 amplification and overexpression as a new prognostic biomarker for early‐stage lung adenocarcinoma

Genetic abnormality in early‐stage lung adenocarcinoma was examined to search for new prognostic biomarkers. Six in situ lung adenocarcinomas and nine small but invasive adenocarcinomas were examined by array‐comparative genomic hybridization, and candidate genes of interest were screened. To examine gene abnormalities, 83 cases of various types of lung carcinoma were examined by quantitative real‐time genomic PCR and immunohistochemistry. The results were then verified using another set of early‐stage adenocarcinomas. Array‐comparative genomic hybridization indicated frequent amplification at chromosome 3q26. Of the seven genes located in this region, we focused on the epithelial cell transforming sequence 2 (ECT2) oncogene, as ECT2 amplification was detected only in invasive adenocarcinoma, and not in in situ carcinoma. Quantitative PCR and immunohistochemistry analyses also detected overexpression of ECT2 in invasive adenocarcinoma, and this was correlated with both the Ki‐67 labeling index and mitotic index. In addition, it was associated with disease‐free survival and overall survival of patients with lung adenocarcinoma. These results were verified using another set of early‐stage adenocarcinomas resected at another hospital. Abnormality of the ECT2 gene occurs at a relatively early stage of lung adenocarcinogenesis and would be applicable as a new biomarker for prognostication of patients with lung adenocarcinoma.     

非小细胞肺癌中乳酸脱氢酶A/B的表达特点及其与肿瘤临床病理参数的关系

目的:探讨非小细胞肺癌中乳酸脱氢酶A/B（lactate dehydrogenase A/B,LDHA/LDHB）表达特征及其与肿瘤临床病理参数的关系。方法:从GEO、TCGA数据库获取非小细胞肺癌、肺腺癌、肺鳞癌基因表达数据及临床信息,通过非参数检验分析LDHA/LDHB在癌组织和正常肺组织的表达差异,通过Kaplan-Meier法和Log-rank test评估癌患者生存状况,采用chi-square test和Spearman's test分析LDHA/LDHB表达与临床特征及肿瘤恶性生物学标志物的关系。结果:LDHA/LDHB在非小细胞肺癌、肺腺癌和肺鳞癌中均高表达。在肺腺癌中,高表达LDHA的病人具有更短的总生存期和无进展生存期,高表达LDHB的病人总生存期更短,LDHA与LDHB均高表达的患者总生存期和无进展生存期皆最短。在肺鳞癌中,LDHA/LDHB表达与生存期无关。在肺腺癌中,LDHA表达与淋巴结转移、肿瘤分期相关,LDHB表达与肿瘤分期相关。在肺鳞癌中,LDHA表达与临床特征关联均不明显,LDHB表达与年龄、淋巴结转移相关。在肺腺癌中,LDHA表达水平与PCNA、Ki67、CDH2正相关,与CDH1无关,而LDHB表达水平与PCNA、Ki67正相关,与CDH2负相关,与CDH1无关。结论:LDHA与LDHB表达和肺腺癌恶性程度相关,高表达LDHA与LDHB可能预示着较差的预后及临床特征。     

Prognostic significance of synaptophysin in stage I of squamous carcinoma and adenocarcinoma of the lung

BACKGROUND: The prognostic significance of the presence of a neuroendocrine marker (synaptophysin, SY) was analyzed in stage I of squamous carcinoma and adenocarcinoma of the lung. METHODS: A multicentric retrospective study was conducted with immunohistochemical staining in a single center of 318 patients resected for squamous carcinoma or adenocarcinoma in pathologic stage I. RESULTS: In all, 162 cases of squamous carcinoma and 156 cases of adenocarcinoma were identified, which included 105 patients in stage IA (50 patients with squamous carcinoma and 55 patients with adenocarcinoma) and 213 in stage IB (112 with squamous carcinoma and 101 with adenocarcinoma). Eighty-six tumors showed a presence of SY+ (27%). Univariate analysis showed lower survival rates at 5 years for those patients older than 70 years of age compared with those patients younger than 70 years of age (60.35% vs 70.57%; P = .007) and for those patients with SY+ compared with those with SY- (52.48% vs 72.68%; P = .0017). Patients with SY+ tumors showed a higher rate of recurrence than patients with SY- tumors (50% vs 33.6%; P = .008). Multivariate analysis showed that those patients greater that 70 years of age (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.14-2.65) and the presence of SY (HR, 2.15; 95% CI, 1.40-3.30) were significant independent prognostic factors associated with a poor outcome. CONCLUSIONS: Stage I of squamous carcinoma and adenocarcinoma of the lung with SY+ has a poor prognosis, with a higher frequency of recurrence and lower survival rates.     

Immunologic parameters as significant prognostic factors in lung cancer

Immunologic prognostic factors in lung cancer have not been fully clarified. We report the results of a prospective study undertaken to clarify the correlation between various cellular immunologic parameters and the survival of lung cancer patients. A total of 287 lung cancer patients were enrolled in this study. Representative in vitro cellular immune activities including lymphoblastogenesis and natural killer cell activities, in addition to the percentage of main lymphocyte subsets (CD3, CD4, CD8, HLA-DR, and Fc gamma R III on T cells) in the peripheral blood were evaluated before the initiation of therapy. The immune factors that influence the prognosis were analyzed by the log rank test and a multivariate analysis using the Cox proportional hazards model. Univariate analysis of the survival curves revealed a significant difference with regard to disease stage (P<0.0001), age (P=0.007), gender (P=0.0037), and HLA-DR (%) (P=0.048), when all the non-small cell lung cancer (NSCLC) patients (n=257) were analyzed together. This analysis, based on the histologic type, revealed that HLA-DR (%) was a significant predictor of survival in squamous cell carcinoma (P=0.0013) and small cell carcinoma (P=0.0025). A decreased CD4/CD8 ratio in small cell carcinoma (P=0.0062) and male gender in adenocarcinoma (P=0.0086) were factors associated with a worse prognosis. Multivariate analysis identified a significant correlation between survival and disease stage (P<0.0001) and gender (P=0.0243) in adenocarcinoma, disease stage (P<0.0001), age (P=0.0436) and HLA-DR (%) (P=0.0142) in squamous cell carcinoma, and HLA-DR (%) (P=0.0212) and CD4/CD8 (P=0.0112) in small cell carcinoma, suggesting independent prognostic significance. A variety of immunologic indices have prognostic significance for the different types of lung cancer. Among these, the HLA-DR (%) in the peripheral blood is the most reliable factor for squamous cell carcinoma and small cell carcinoma.     

Clinicopathologic characteristics of adenosquamous carcinoma of the lung

Fifty-six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically, and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of adenosquamous carcinoma was 2.6% of 2160 primary lung cancers resected in the National Cancer Center Hospital (Tokyo, Japan). The survival curves of patients with adenosquamous carcinomas, adenocarcinomas, and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas, particularly in Stages I and II. The amount of adenocarcinoma component did not affect the survival rate, although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors. The histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants.     

Is adenocarcinoma/large cell carcinoma the most radiocurable type of cancer of the lung?

Radiation therapy is widely considered the primary treatment for inoperable "non-small" cell carcinoma of the lung. In clinical investigations, distinction has been infrequent among the histopathologic subtypes of non-small cell carcinoma. Studies have shown significant differences between squamous cell carcinoma and adenocarcinoma/large cell carcinoma; adenocarcinoma/large cell carcinoma has a greater propensity for extrathoracic dissemination, especially to the brain, and it is less curable by resection when regional lymph node metastases are present. No differences have been documented between adenocarcinoma and large cell carcinoma. A retrospective study was undertaken to determine the results of definitive radiation therapy by histopathologic subtype of non-small cell carcinoma of the lung. Between July 1977 and April 1983, 134 patients with non-small cell carcinoma of the lung underwent definitive radiation therapy with curative intent. All patients had performance status scores of 80 to 100 (Karnofsky), and received minimum total doses within the tumor of 60 Gy in 6 to 7 weeks, five fractions per week. The median period of observation was 63 months. Ninety patients had squamous cell carcinoma; 44 had adenocarcinoma/large cell carcinoma. The two groups of patients were comparable in respect to age and Stage; there were significantly more women with adenocarcinoma/large cell carcinoma (27%) than with squamous cell carcinoma (13%). The median survival for patients with squamous cell carcinoma was 11.5 months; the 2 and 4 year survival rates were 21 and 7%, respectively. The median survival for patients with adenocarcinoma/large cell carcinoma was 18 months; 2 and 4 year survival rates were 38 and 23%, respectively. Comparison of the overall survival experience did not show a significant difference between the two cell types (p = .12 using Gehan's generalized Wilcoxon test). However, comparison of the proportion of patients with adenocarcinoma/large cell carcinoma surviving 18 months (50%) was significantly higher (p = .02) than that with squamous cell carcinoma (30%). A small body of data from the literature also suggests a better long-term prognosis for adenocarcinoma/large cell carcinoma. This observation requires confirmation from large trials with histopathologic review. If it is confirmed, there are important implications for therapeutic strategies in future clinical investigations of inoperable carcinoma of the lung.     

Fast-neutron radiotherapy of nonsmall cell-carcinoma of the lung

To determine the efficacy of fast neutron (FN) for the treatment of non-small cell lung cancer, 112 patients with histologically proven adenocarcinoma or squamous cell carcinoma at a limited stage were studied to evaluate local control and survival, after treatment with either FNs or photons alone. The local control rate of adenocarcinoma in FN-treated patients attained 50%, which was significantly higher than that (<10%) of squamous cell carcinoma in FN-treated patients or that of both histological types of carcinoma in patients treated with photons alone. In accordance with this, the 5-year survival rate for the FN-treated patients with adenocarcinoma was significantly higher than that for FN-treated patients with squamous cell carcinoma or that for photon-treated patients with both histological types of disease. The present study clearly suggests the usefulness of FN in the treatment of adenocarcinoma of the lung, though it was a non-randomized trial.     

肺鳞癌与腺癌非手术治疗预后差异的原因分析

目的分析非手术治疗的肺鳞癌与腺癌预后差异的原因。方法１９９０年１２月～１９９４年１２月间以根治性放疗为主的非手术治疗１７７例肺癌（鳞癌１２５例，腺癌５２例），采用Ｋａｐｌａｎ－Ｍｅｔｅｒ计算方法和Ｃｏｘ多因素分析方法分析鳞癌和腺癌的生存率、肿瘤局部控制率、无远处转移率，并进行比较。结果１年和２年生存率，肺鳞癌为８０．３％和４４％，显著高于腺癌的５５．４％和１７．２％（Ｐ＜０．００１）；１年和２年局部控制率，肺鳞癌为７９．５％和４３．４％，肺腺癌为５４．３％和２７．６％（Ｐ＝０．００７）；１年和２年无远处转移率，肺鳞癌为８６％和７３．９％，腺癌为６２．８％和２２．９％（Ｐ＜０．００１）。Ｃｏｘ多因素分析结果表明组织学类型在生存率、局部控制率、无远处转移率三项指标中均有显著差异（产均＜０．０１）。结论在非手术治疗中，肺鳞癌较腺癌患者预后好；预后差异的原因在于鳞癌局部控制率高而远处转移率低。     

Lung cancer prognostic factors from the Aichi Cancer Registry

Lung cancer prognostic factors have been evaluated on the basis of three-year survival rates for 2,830 lung cancer patients diagnosed between 1983 and 1986 and reported to the Aichi Cancer Registry. In the univariate analyses, the former in each pair of following factors showed a significantly better prognosis than the latter: early vs. late stage of disease, surgically-treated vs. non-surgically-treated cases, adenocarcinoma and squamous cell carcinoma vs. large cell and small cell carcinoma, cases detected by screening vs. others, young vs. old patients, females vs. males, non-smokers vs. smokers. The association of prognosis with these factors, other than smoking and histological type, remained statistically significant throughout multivariate analysis. When analyzed according to histological type, disease stage was the most important prognostic factor, across all histological types, and surgery was the second most important prognostic factor, except in cases of small cell carcinoma. Sex and method of detection were significantly associated with survival rates in adenocarcinoma and small cell carcinoma, and the association with smoking was of borderline significance for adenocarcinoma.     

The association between atypical adenomatous hyperplasia and primary lung cancer

Atypical adenomatous hyperplasia (AAH) has been suggested as the adenoma in an adenoma-carcinoma sequence in the lung periphery. From 1989-1998, we undertook a systematic, prospective search for AAH in lungs resected for cancer. AAH was found in 67 of 554 patients (12. 1%) with primary lung carcinoma (9.2% in male patients and 19.0% in females). AAH was found in lungs bearing adenocarcinoma (23.2%) more frequently than with large cell undifferentiated carcinoma (12.5%) or squamous carcinoma (3.3%). A greater percentage of females with adenocarcinoma had AAH (30.2%) than did males with adenocarcinoma (18.8%). Numbers of AAH ranged from 1-42 per patient and more patients had small numbers of AAH, although 12 patients had 6 or more AAH foci. Larger numbers of AAH tended to be found in adenocarcinoma-bearing lungs. Ten of the 67 patients with AAH and primary lung carcinoma (15%) had multiple primary cancers (range 2-6), all of which were adenocarcinoma. Synchronous cancers were rare in lung tumour-bearing resections without AAH. Patients with AAH show no difference in post-operative survival to those without, for all stages of carcinoma and for Stage I disease alone. This study provides evidence for a strong association between atypical adenomatous hyperplasia and primary lung adenocarcinoma and lends weight to the AAH/adenoma-carcinoma hypothesis.     

135例食管鳞癌肺转移预后因素分析

目的:探讨食管鳞癌肺转移患者预后的影响因素。方法:回顾性分析2008—2018年间浙江省肿瘤医院135例食管鳞癌治疗后肺转移患者的临床特点。运用 Kaplan- Meier法计算生存率, log- rank法单因素预后分析, Cox模型多因素预后分析。 ...