Prognostic and clinicopathological significance of SR-B1 in solid tumors: A meta-analysis

BackgroundThe expression of cell surface receptors is abnormal in malignant tumors. The scavenger receptor class B type I (SR-B1) is an integral membrane glycoprotein receptor that facilitates the selective uptake of cholesterol by malignant cells. Accumulated studies investigated the prognostic role of SR-B1 in many solid tumors, such as breast cancer, lung cancer and so on. However, the conclusions remain undefined. Therefore, we conducted this meta-analysis to obtain more accurate evaluation of prognostic significance of SR-B1 in solid tumors.Materials and methodsWe searched PubMed, Embase, Web of science and Cochrane library for eligible studies published before November 2018. The included studies investigated the association between the SR-B1 level and clinicopathological features including survival outcomes in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were adopted to assess the survival outcomes and odds ratio (ORs) with 95% confidence intervals (CIs) were pooled to evaluated the clinicopathological features.ResultsA total of 10 studies involving 2585 patients were included in this meta-analysis. The results showed that low SR-B1 level was significantly correlated with earlier tumor grade (pooled OR = 2.09, 95%CI = 1.28–3.43, P = 0.001), less nodal involvement (pooled OR = 2.07, 95%CI = 1.43–3.0, P < 0.001), less distant metastasis (OR = 19.8, 95%CI = 2.58–151.65, P = 0.004), smaller tumor size (OR = 2.34, 95%CI = 1.53–3.57, P < 0.001), earlier TNM stage (OR = 3.77, 95%CI = 1.67–8.48, P = 0.001), lower recurrence (HR = 1.98, 95%CI = 1.57–2.49, P = 0.000), and better OS (HR = 1.99, 95%CI = 1.70–2.31, P = 0.000).ConclusionThe low expression of SR-B1 was significantly associated with better clinicopathological status and longer survival in patients with solid tumors. SR-B1 might act as a promising prognostic biomarker for solid tumors.     

Prognostic and clinicopathological significance of CapG in various cancers: Evidence from a meta-analysis

BackgroundThe gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in various types of cancer. However, the role of CapG in malignant tumors is still controversial. Therefore, we conducted a meta-analysis to assess the prognostic value and clinicopathological significance of CapG in malignant tumors.MethodWe searched for eligible studies in the PubMed, Web of Science, Embase, and Cochrane databases. Stata SE12.0 software was used for quantitative meta-analysis. The hazard ratios (HRs) and odds ratios (ORs) with 95% CI were pooled to assess the relationship between CapG expression and overall survival (OS), as well as clinicopathological parameters.ResultsSixteen studies with a total of 1987 cancer patients were included in this meta-analysis. The results showed that higher CapG expression was statistically correlated with shorter OS (HR 1.70, 95% CI 1.43–1.97, P < 0.001), positive lymph node metastasis (OR 1.91, 95% CI 1.19–3.09, P = 0.008), advanced TNM stage (OR 1.87, 95% CI 1.17–3.00, P = 0.009), advanced T-primary stage (OR 2.54, 95% CI 1.08–6.00, P = 0.033) and male sex (OR 1.77, 95% CI 1.23–2.56, P = 0.002). However, no significant correlation was observed between increased CapG expression and advanced age, larger tumor size, differentiation, or advanced histopathologic grading (P > 0.05).ConclusionsHigh CapG expression is associated with a poor prognosis and worse clinicopathological parameters in various cancers. CapG is a potential prognostic biomarker and a possible clinicopathological predictive factor for various cancers.     

Association between GPX3 promoter methylation and malignant tumors: A meta-analysis

Glutathione peroxidase 3 (GPX3) has an important function of scavenging hydrogen peroxide and preventing cancer. The purpose of this meta-analysis was to analyze the relationship between GPX3 gene methylation and cancer and to further evaluate its diagnostic value for cancer. We screened eligible literatures from the PubMed, Embase, CNKI and Wanfang databases. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to measure the association of GPX3 methylation with cancer. Summary receiver operating characteristics (SROC) analysis was used to assess the diagnostic value of GPX3 methylation for cancer. A total of 17 eligible articles were included in the meta-analysis involving a total of 960 tumor samples and 445 non-tumor samples. The results showed that GPX3 hypermethylation was significantly associated with cancer (OR = 17.32, 95% CI = 8.22–36.51, P < 0.00001). Compared with cancer patients without lymph node metastasis, cancer patients with lymph node metastasis were more associated with GPX3 hypermethylation (OR = 2.97, 95% CI = 1.53–5.76, P = 0.001). SROC analysis showed for GPX3 methylation was a promising biomarker for cancer risk (AUC = 0.89, pooled sensitivity = 0.93, pooled specificity = 0.54, NLR = 0.15, PLR = 2.05, DOR = 17.32). TCGA database bioinformatics analysis of 696 pairs of tumor and non-tumor tissues further validate the association of GPX3 methylation with the risk of cancer [cg21504918: 0.10 (0.08, 0.15) vs. 0.09 (0.08, 0.11), P = 5.8E-28; cg26638444: 0.05 (0.04, 011) vs. 0.04 (0.03, 0.06), P = 8.7E-29]. In summary, our study indicates that GPX3 methylation is associated with cancer and has the potential to become a broad-spectrum tumor screening marker and has a value in predicting tumor lymph node metastasis.     

Prognostic value of long non-coding RNA FOXD2-AS1 expression in patients with solid tumors

BackgroundAlthough increasing evidence has revealed that FOXD2-AS1 overexpression exists in various solid tumors, the value of FOXD2-AS1 as a prognostic marker in such cancers remains uncertain. Accordingly, the present research aimed to assess the association of FOXD2-AS1 with cancer prognosis and predict the biological function of FOXD2-AS1.MethodsWe systematically retrieved PubMed, PMC, Web of Science, EMBASE and Wiley Online Library databases for eligible articles published up to December 2018. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to evaluate the correlation of FOXD2-AS1 expression with overall survival (OS), disease free survival (DFS) and clinicopathological characteristics. We also used five Gene Expression Omnibus (GEO) datasets from breast cancer patients to explore the relationship between FOXD2-AS1 expression and prognosis. Finally, we validated FOXD2-AS1 expression in various carcinomas and predicted its biological function based on the public databases.ResultsA total of 13 studies with 2502 tumor patients were included. The pooled HRs demonstrated that FOXD2-AS1 overexpression was significantly associated with unfavorable OS (HR = 1.39, 95%CI: 1.23–1.57, p < 0.001) and DFS (HR = 2.24, 95%CI: 1.55–3.23, p < 0.001) in tumor patients. The pooled ORs indicated that FOXD2-AS1 upregulation was related to large tumor size (OR = 1.53, 95%CI: 1.26–1.85, p < 0.001), deep invasion depth (OR = 1.99, 95%CI: 1.53–2.58, p < 0.001), distant metastasis (OR = 2.03, 95%CI: 1.69–2.43, p < 0.001) and advanced TNM stage (OR = 1.35, 95%CI: 1.06–1.72, p = 0.0150), but not to lymph node metastasis nor differentiation. Moreover, a similar pooled result for the OS of breast cancer patients was obtained (HR = 1.55, 95%CI: 1.14–2.11, p = 0.0052) by analyzing GEO data. Finally, elevated FOXD2-AS1 expression in various solid tumor tissues was verified based on The Cancer Genome Atlas (TCGA) data. Further functional prediction demonstrated that FOXD2-AS1 may participate in some cancer-related pathways.ConclusionElevated FOXD2-AS1 expression was associated with poor survival in patients with solid tumors and may serve as a potential prognostic biomarker for a variety of cancers.     

Elastin turnover in malignant solid tumors

Abstract

Desmosine, a crosslinking amino acid unique to elastin, was investigated as a possible biomarker for cancer. Twenty-eight normal controls, median age 67 years, had a median value for urine desmosine of 43.5 picomoles desmosine/mg creatinine. The median for 19 untreated cancer subjects of similar age was significantly higher (175 picomoles desmosine/mg creatinine, p?<?0.001). Urine desmosine levels in 55 subjects currently receiving chemotherapy, as well as 67 individuals who had survived cancer and were currently clinically disease free, were not significantly different from controls. Our findings indicate that elastin is being turned over in malignant solid tumors, releasing significantly elevated levels of desmosine in the urine.     

Prognostic value of microRNA-451 in various cancers: A meta-analysis

BackgroundIncreasing evidence shows microRNA-451 plays a crucial role in various tumors, but there is inconsistency. The aim of this study was to explore the prognostic role of miR-451 in various tumors.MethodsOnline PubMed, EMBASE, Web of Science, and the Cochrane library database were searched through February 2019. Hazard ratios (HRs) were extracted and used to describe the association between expression of microRNA-451 and survival outcome, and the correlation between microRNA-451 and clinicopathologic features were described by pooled odds ratios (ORs).ResultsSixteen retrospective studies containing 2122 patients were incorporated in this meta-analysis. High expression of miR-451 was considered statistically associated with prolonged overall survival (OS) (HR = 0.62, 95% CI 0.49-0.80, p < 0.001) as well as RFS/DFS (HR = 0.55, 95% CI 0.42-0.71, p < 0.001) compared with low expression of miR-451. Besides, the pooled ORs revealed significant association between high expression of miR-451 with lymph node invasion (yes vs. no) (OR = 0.64, 95% CI 0.46-0.90, P = 0.01), tumor diameter (big vs. small) (OR = 0.77, 95% CI 0.60-0.97, P = 0.028) and tumor stage (III + IV vs. I + II) (OR = 0.62, 95% CI 0.42-0.93, P = 0.019).ConclusionMicroRNA-451 may serve as a promising clinical prognostic biomarker in various carcinomas.     

Prognostic value of osteopontin expression in esophageal squamous cell carcinoma: A meta-analysis

ObjectiveTo explore the prognostic role of osteopontin (OPN) overexpression in esophageal squamous cell carcinoma (ESCC).MethodsThe PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chinese Biomedical Data (CBM) and VIP databases were searched from the establishment dates of the databases to March 31, 2019, for potentially related studies. Stata 12.0 software was used for statistical analyses, and the hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the correlation of OPN overexpression with the overall survival (OS) and progression-free survival (PFS) of ESCC patients.ResultsA total of 8 studies involving 811 patients from China or Japan were included. OPN overexpression was demonstrated to be significantly associated with poor OS (HR = 1.86, 95% CI: 1.22–2.83, P = 0.004), with high heterogeneity (I² = 61.2%, P = 0.012), and poor PFS (HR=1.63, 95% CI: 1.08–2.47, P = 0.020), without heterogeneity (I² = 0.0%, P = 0.839). Subgroup analysis results were similar to the pooled results.ConclusionOPN overexpression might serve as a promising independent prognostic risk factor in Chinese and Japanese ESCC patients. However, more well-designed studies enrolling more patients are still needed to verify our findings.     

Long noncoding RNAs in bladder cancer prognosis: A meta-analysis

BackgroundNumerous studies have demonstrated the involvement of long non-coding RNAs (lncRNAs) in the tumorigenesis of bladder cancer (BC). The aim of this study was to investigate the possible correlations between the specific lncRNAs and the clinical outcomes in bladder cancer patients.MethodsWe systematically searched the PubMed, EMBASE and the Cochrane Library databases for studies published up to October 15, 2018, and retrieved the suitable articles. Pooled odds ratios (ORs), hazard ratios (HRs) and 95% confidence intervals (95% CIs) were obtained by using fixed-effect or random-effect model.ResultsUp-regulation of lncRNAs predicted unfavorable overall survival (OS) (HR: 2.01, 95%CI: 1.66–2.44, P < 0.001) and recurrence-free survival (RFS) (HR: 2.05, 95%CI: 1.43–2.94, P < 0.001) in BC patients, and the high expression of lncRNAs was significantly associated with distant metastasis (DM) (OR: 8.16, 95%CI: 4.45–14.99, P < 0.001).ConclusionAbnormal expression of relevant lncRNAs are potential novel markers for predicting the clinical outcomes of BC.     

The diagnostic and prognostic significance of long noncoding RNAs expression in thyroid cancer: A systematic review and meta-analysis

Objective

Thyroid cancer (TC) is the most common malignant endocrine-related cancer with an increasing trend worldwide. Therefore, it’s in urgent need to find new markers for prognosis and diagnosis. Many long noncoding RNAs (lncRNAs) have been reported to be aberrantly expressed in TC, and may serve as biomarkers. Therefore, we performed this meta-analysis to systematically summarize the relationship between lncRNA expressions and TC.

The clinicopathological significance of SIRT1 expression in colon cancer: An immunohistochemical study and meta-analysis

Objective

The aim of this study was to determine the clinicopathological significance and potential prognostic role of SIRT1 expression in colorectal cancer (CRC) using immunohistochemistry and meta-analysis.

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.     

Effect of fibroblast interferon on colony tumor growth of miscellaneous solid human tumors

Summary The antiproliferative effect of fibroblast interferon (IF-) on the colony tumor growth of 42 miscellaneous carcinomas (15 gastric, 11 breast, eight colon, five ovarian, three bronchial) and two malignant melanomas were assayed in a semisolid, double-layered agar culture system. Of the 44 evaluable experiments only four tumor specimens (three breast-, one gastric carcinoma) showed at least a 30% inhibition of colony formation due to application of interferon at concentration of 1,000 IU/ml or less. In these cases, a dose response relationship of the interferon effect was obvious. Yet, in the majority of carcinomas investigated, interferon had no antiproliferative influence on colony tumor growth and was markedly inferior to a simultaneously tested cytostatic agent (adriamycin). Our in vitro results contradict a general direct cytotoxic action of interferon on human solid carcinomas.     

Golgi phosphoprotein3 overexpression is associated with poor survival in patients with solid tumors: a meta-analysis

Golgi phosphoprotein3 (GOLPH3) is known as an oncoprotein and may be a prognostic biomarker in various tumors. Here we performed a meta-analysis on the association of GOLPH3 expression and survival in solid tumors. All eligible studies were identified in Embase, PubMed and Web of Science Databases up to November 2014. Data about overall survival (OS), and disease-free survival (DFS) were extracted and pooled hazard ratios (HRs) of GOLPH3 for survival were calculated by using a random-effect model. Heterogeneity and publication bias were also assessed. A total of 15 eligible studies which comprised of 2529 cases were included in this global analysis: 14 were dealing with overall survival (OS) and 6 were with disease-free survival (DFS). We found that GOLPH3 overexpression was associated with shorter OS (HR 2.487, 95% CI 1.897-3.258, P < 0.001) and DFS (HR 1.911, 95% CI 1.245-2.932, P = 0.003) in general carcinomas. Importantly, subgroup analysis suggested that overexpression of GOLPH3 correlated with shorter OS in urogenital system cancers (HR 4.258, 95% CI 1.81-4.91, P < 0.001). Moreover, publication bias was not significant (P > 0.05). In conclusion, the present meta-analysis showed that overexpression of GOLPH3 predicts poor prognosis in solid tumors.     

N-cadherin expression in adrenal tumors: upregulation in malignant pheochromocytoma and downregulation in adrenocortical carcinoma

Cell adhesion molecules (CAMs) are important regulators of tumor growth. The aim of the present study was to evaluate the expression pattern of CAMs in adrenal tumors regarding origin (cortex vs medulla) and biologic behavior (benign vs malignant). Eighty-seven adrenal tumors were investigated by immunocytochemistry (ICC) using monoclonal antibodies against N-cadherin (NCAD), E-cadherin (ECAD), neural cell adhesion molecule (NCAM), and CD44. Western blotting was performed on 30 tumors using the same antibodies. Markers for proliferation (Ki-67) and catecholamine synthesis (tyrosine hydroxylase) were also analyzed in tumors by ICC. NCAD was expressed in 12/27 benign pheochromocytomas (BPCs) (12 familial cases), 8/8 malignant pheochromocytomas (MPCs), 28/30 adrenocortical adenomas, and 9/22 adrenocortical carcinomas. ECAD was expressed in 0/27 BPCs, 0/8 MPCs, 0/30 adrenocortical adenomas, and 2/22 adrenocortical carcinomas. NCAM was expressed in 26/27 BPCs, 7/8 MPCs, 21/30 adrenocrotical adenomas, and 17/22 adrenocortical carcinomas. CD44 was expressed in 23/27 BPCs, 6/8 MPCs, 7/30 adrenocortical adenomas, and 4/22 adrenocortical carcinomas. Both cortical and medullary adrenal tumors expressed NCAD, NCAM, and CD44 but were devoid of ECAD. The expression of CD44 and NCAM did not correlate with the malignant potential of tumors. NCAD was upregulated in MPCs, but downregulated in adrenocortical carcinoma. Thus, NCAD appears to be involved in the development of both cortical and medullary adrenal tumors.     

Prognostic indicators in pituitary tumors

Recent advances in molecular pathology have shed light not only on the cellular composition and derivation of various tumors, but also on their growth potential, likelihood of recurrence, and prognosis. The development of reliable and prognostically informative methods of assessing tumor behavior is particularly important in pituitary tumors, where no precise correlation exists between morphology and clinical aggressiveness. Among the numerous morphologic techniques that have been introduced in the last three decades, some have gained popularity due to their reliability and ease of performance, whereas others have fallen from favor due to their inconsistency and insensitivity in distinguishing indolent from aggressive pituitary tumors. Yet others, due to cost and complexity, never came into general use. We predict that the immunohistochemical methods now in use for assessment of tumor behavior will be complemented and partly replaced by molecular genetic procedures in the future.     

Prognostic value of long non-coding RNA ATB in digestive system cancers: A meta-analysis

BackgroundThe present meta-analysis has evaluated the association between lncRNA ATB, prognosis and clinicopathological parameters in patients with digestive cancers.MethodsEligible studies were gathered from Web of Science, PubMed, Embase, Cochrane Library, WanFang databases and China National Knowledge Infrastructure (up to October 15, 2019). Hazard ratios (HRs) and 95 % confidence intervals (CIs) were calculated to estimate the prognosis and clinicopathological parameters of lncRNA ATB in patients with digestive cancers.ResultWe divided this study into two groups, pancreatic cancer (PC, downregulation) and non-pancreatic cancer (non-PC, upregulation). In the non-PC group, high expression levels of lncRNA ATB were significantly related to poor OS (pooled HR = 2.19, 95 % CI 1.68–2.85, P＜0.00001). In contrast, increased levels of lncRNA ATB in pancreatic cancer tissue were favorable factors in OS (HR = 0.47, 95 % CI 0.32−0.69, P = 0.0001). The pooled data suggested that high expression levels of lncRNA ATB predicted a poor DFS in CRC and a poor RFS in HCC. Increased expression of lncRNA ATB was correlated with negative lymph node metastasis and TNM stage in the non-PC group. In contrast, lncRNA ATB were favorable factors for LNM and TNM stages in pancreatic cancer.ConclusionLncRNA ATBs, whether cancer promoters or suppressors, were potential biomarkers and therapeutic targets for digestive system cancers.     

Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis

Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent.We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated.An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106−1.397; P_{heterogeneity}=0.001) from multivariate studies and 1.867 (95%CI: 1.487−2.344; P_{heterogeneity}=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061−1.399; P_{heterogeneity}=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156−2.077; P_{heterogeneity}=0.625) in multivariate studies.The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer.     

Soluble intercellular cell adhesion molecule-1 in lung cancer: A meta-analysis

BackgroundMany recent studies have investigated the prognostic, diagnostic, and progressive features of soluble intercellular cell adhesion molecule-1 (sICAM-1) in lung cancer patients, but the results remained inconsistent. This study aimed to explore the value of serum sICAM-1 in patients with lung cancer.MethodsA comprehensive systematic literature search in the Wanfang databases, china national knowledge infrastructure, Pubmed, and Embase was carried out update to June 15, 2019. The standard mean difference (SMD), hazard ratio (HR), and 95% confidence interval (95% CI) were applied to investigate the effect sizes.Results23 observational studies were included. According to our results, the serum sICAM-1 concentrations in patients with lung cancer were significantly higher than that in controls (healthy controls: SMD: 4.08, 95% CI: 3.14–5.02, P < 0.001; benign lung diseases controls : SMD: 1.48, 95% CI: 0.23–2.73,P = 0.02). Fortunately, a subgroup analysis was performed by language, treatment status, and lung cancer types, and the statistical results were similar. Serum sICAM-1 levels were markedly higher in stage III/IV than stage I/II (SMD: 1.96, 95% CI: 1.08−2.84, P < 0.001), Additionally, lung cancer patients with lymph node metastasis had a higher concentrations of serum sICAM-1(SMD: 1.83, 95% CI: 0.95−2.72, P < 0.001), as well as with distant metastasis (SMD: 0.86, 95% CI: 0.47−1.25, P < 0.001). Additionally, patients with higher sICAM-1 levels were related to a significantly poorer prognosis (progression free survival: HR: 1.16, 95% CI: 1.07–1.26, P < 0.001; overall survival: HR: 1.45, 95% CI: 1.17–1.79, P = 0.001).ConclusionsOur study suggested that serum sICAM-1 levels may act as a potential marker for diagnosing lung cancer and predicting its staging, and were negatively correlated with prognosis of lung cancer.     

Prognostic implications of ploidy and proliferative activity in human solid tumors

Ploidy and cell cycle compartment distribution were measured by DNA flow cytometry in 261 patients with a variety of different tumors. Eighty-one percent of all tumors were aneuploid, and 72% were hyperdiploid. Ploidy levels spanned a wide range from hypodiploid (maximum 30% < diploid controls) to hyperoctaploid (440% in excess of diploid controls) with mean and median values coinciding at a near-triploid DNA content. The proportion of cells with G₁ DNA content decreased with increasing hyperdiploid abnormality. While unrelated to biopsy site and to a number of host factors such as age, sex and race, both ploidy and cytokinetic parameters were markedly affected by histopathologic diagnosis. Patients with metastatic lung, breast, and GI cancer had higher ploidy levels than individuals with the corresponding primary tumors. Ploidy (except for one patient) remained constant, and G_1/0 proportions showed only minor variation by disease site and over a median observation time of 6 months. Prognostic factor analysis was performed in the subgroup of patients studied within 6 months from diagnosis. The adverse impact of low tumor G_1/0 proportion on survival was lost as the proportional hazard analysis was extended to include diagnostic subgroups. Accounting for histopathologic diagnosis, stage of disease, ploidy, and the proportion of tumor G_1/0 cells, the following sequence of adverse prognostic factors in order of their relative ranks was established: (1) absence of breast cancer (p = 0.001), (2) hypertriploid DNA index (p = 0.049), and (3) presence of metastatic disease (p = 0.079). Our study demonstrates that DNA content-derived information on instrinsic tumor cell features pertaining to cytogenetics and cytokinetics may provide an objective means of biologically relevant cancer classification.