Clinicopathological Significances of Tumor-Stroma Ratio (TSR) in Colorectal Cancers: Prognostic Implication of TSR Compared to Hypoxia-Inducible Factor-1α Expression and Microvessel Density.
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ABSTRACT:
SUBMITTER: Kang G
PROVIDER: S-EPMC8025820 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCurrent reports on the prognostic and predictive value of hypoxia-inducible factor-1α (HIF-1α) in endometrial carcinoma are inconsistent. Therefore, we conducted this meta-analysis to precisely evaluate the association of HIF-1α expression with susceptibility, clinical features, and prognosis of endometrial cancer.MethodsEligible studies that assessed the role of HIF-1α protein expression, immunohistochemistry detection, disease susceptibility, clinical features, and prognosis of endometrial cancer were searched from the Embase, Pubmed, and Web of Science databases. Stata 14.0 software was used to merge and compute pooled hazard ratios (HR) and odds ratios (OR). Information including HIF-1α protein expression and clinical progression of endometrial cancer was extracted. The pooled HR and OR with corresponding 95% confidence intervals (CI) were used to estimate the strength of these associations.ResultsA total of 25 studies were included in the analysis. HIF-1α protein expression in endometrial cancer tissue was significantly higher than that in normal tissues (OR = 15.79, 95% CI = 8.44-29.52, P < 0.05). Endometrial cancer patients with higher HIF-1α protein expression had poorer prognosis compared to patients with low HIF-1α protein expression (HR = 2.29, 95% CI = 1.68-2.90, P < 0.05). In addition, high HIF-1α protein expression was significantly associated with endometrial cancer grade, lymph node metastasis, and myometrial invasion (grade in Caucasians: OR = 3.09, 95% CI = 1.63-5.85, P < 0.05; lymph node metastasis: OR = 3.09, 95% CI = 1.63-5.85, P < 0.05; myometrial invasion: OR = 2.26, 95% CI = 2.15-5.08, P < 0.05).ConclusionsHIF-1α overexpression was significantly associated with increased risk, advanced clinical progression, and poor prognosis in endometrial cancer patients.
| S-EPMC7693720 | biostudies-literature
Project description:BackgroundGynecological cancer is characterized by tumor hypoxia. However, the role of hypoxia-inducible factor 1α (HIF-1α) in gynecological cancer remains unclear.MethodElectronic databases including Cochrane Library, PUBMED, Web of Knowledge and clinical trial registries were searched from inception through October 2014 for published, case-control studies assessing the association between HIF-1α and the clinicopathological characteristics of gynecological cancer. We pooled results from 59 studies using fixed or random-effects models and present results as odds ratios (ORs) following the PRISMA guidelines.ResultsOur meta-analysis, which included 6,612 women, demonstrated that the expression of HIF-1α was associated with the clinicopathological characteristics of gynecological cancer. The expression of HIF-1α in cancer or borderline tissue was significantly higher than that in normal tissue (cancer vs. normal: odds ratio (OR) =9.59, 95% confidence interval (CI): 5.97, 15.39, p<0.00001; borderline vs. normal: OR=4.13, 95% (CI): 2.43, 7.02, p<0.00001; cancer vs. borderline: OR=2.70, 95% (CI): 1.69, 4.31, p<0.0001). The expression of HIF-1α in III-IV stage or lymph node metastasis was significantly higher than that in I-II stage or that without lymph node metastasis, respectively (OR=2.66, 95% (CI): 1.87,3.79, p<0.00001; OR= 3.98, 95% (CI): 2.10,12.89, p<0.0001). HIF-1α was associated with histological grade of cancer (Grade 3 vs. Grade 1: OR=3.77, 95% (CI): 2.76,5.16, p<0.00001; Grade 3 vs. Grade 2: OR=1.62, 95% (CI): 1.20,2.19, p=0.002; Grade 2 vs. Grade 1: OR=2.34, 95% (CI): 1.82,3.00, p<0.00001),5-years disease free survival (DFS) rates (OR=2.93, 95% (CI):1.43,6.01, p=0.001) and 5-years overall survival (OS) rates (OR=5.53, 95% (CI): 2.48,12.31, p<0.0001).ConclusionHIF-1α is associated with the malignant degree, FIGO stage, histological grade, lymph node metastasis, 5-years survival rate and recurrence rate of gynecological cancer. It may play an important role in clinical treatment and prognostic evaluation.
| S-EPMC4438056 | biostudies-literature
Project description:BackgroundHepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients.MethodsWe systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the I 2 statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger's test.ResultsHIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor-node-metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration.ConclusionsHIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers.
| S-EPMC7874357 | biostudies-literature
Project description:BACKGROUND:Recently, many studies have shown the role of hypoxia-inducible factor-1α (HIF-1α) expression in the outcome of bone tumor. However, the results remain inconclusive. It is necessary to carry out a meta-analysis of all the current available data to clarify the relationship between HIF-1α and survival or clinicopathological features of bone tumor. METHODS:PubMed, Cochrane Library, Web of Science, China National Knowledge Internet, and Wanfang databases were used to search the relationship between HIF-1α and bone tumor. Articles investigating clinicopathological and prognostic value of HIF-1α in bone tumor patients were enrolled in this meta-analysis. Overlapping articles, duplicate data, reviews, case reports, and letters without original data were excluded. The pooled risk ratios (RRs) and hazard ratios (HRs) were used to evaluate the clinicopathological and prognostic value of HIF-1α on bone tumor patients, respectively. RESULTS:A total of 28 studies including 1443 patients were included in this meta-analysis, which were involved in three different types of bone tumor including 3 chondrosarcomas, 2 giant cell tumors of bone, and 23 osteosarcomas. Our results showed that high expression levels of HIF-1α were associated with poorer OS (overall survival) (HR = 2.61, 95% CI 2.11-3.23, P < 0.001) and shorter DFS (disease-free survival) (HR = 2.02, 95% CI 1.41-2.89, P < 0.001) in bone tumor. In addition, this study also analyzed the role of HIF-1α expression in clinicopathological features, which were closely related with the severity of bone tumor, including differentiation, clinical stage, metastasis, and microvessel density. Our results indicated that HIF-1α overexpression was significantly associated with differentiation (RR = 1.56, 95% CI 1.00-2.43, P = 0.049), clinical stage (RR = 1.75, 95% CI 1.25-2.45, P = 0.001), metastasis (RR = 1.78, 95% CI 1.58-2.00, P < 0.001), and microvessel density (SMD = 2.34, 95% CI 1.35-3.34, P < 0.001) of bone tumor. CONCLUSIONS:HIF-1α overexpression indicated an unfavorable factor for OS and DFS in bone tumor, suggesting that HIF-1α may serve as a potential prognostic marker for bone tumor.
| S-EPMC6381668 | biostudies-other
Project description:Purpose: We previously reported that polyploid giant cancer cells (PGCCs) induced by cobalt chloride (CoCl2) exhibit cancer stem cell properties. Daughter cells generated by PGCCs possess epithelial mesenchymal transition (EMT) phenotype changes and EMT plays an important role in cancer development and progression. This study investigated the characteristics of PGCCs from LoVo and HCT116 induced by CoCl2 and the clinicopathological significances of PGCCs in colorectal cancer (CRC). Materials and Methods: Western blotting and immunocytochemical staining were used to compare the expression levels of EMT-related proteins between PGCCs with budding daughter cells and the control cells. In addition, tissue samples were collected from 159 patients with CRC for analysis of PGCCs, vasculogenic mimicry (VM), and single stromal PGCCs with budding, as well as immunohistochemical staining for cathepsin B, vimentin, and hemoglobin A. Results: Single PGCCs induced by CoCl2 formed spheroids in vitro. Poorly differentiated CRCs showed the highest numbers of PGCCs and VM, and expression of cathepsin B. There was greater expression of EMT-related proteins in PGCCs with budding daughter cells than in control cells. The expression of vimentin located in PGCC nuclei. Single stomal PGCCs with budding were detected in 27.45% of well differentiated, 50% of moderately differentiated, and 90.20% of poorly differentiated CRC samples. PGCCs can generate erythroid cells that express delta-hemoglobin to form VM. Erythroid cells generated by PGCCs were positive for hemoglobin A immunocytochemical staining. Conclusion: PGCCs from LoVo and HCT116 treated by CoCl2 exhibited cancer stem cell properties. The number of PGCCs and VM were associated with CRC differentiation and daughter cells budded from PGCCs may promote the lymph node metastasis via expression of EMT-related proteins. PGCCs and their newly generated erythroid cells form VM structures.
| S-EPMC5332899 | biostudies-literature
Project description:Tumor-to-stroma ratio (TSR) is a prognostic factor that expresses the relative amounts of tumor and intratumoral stroma. In this study, its clinical and molecular relevance was evaluated in prostate cancer (PCa). The feasibility of automated quantification was tested in digital scans of tissue microarrays containing 128 primary tumors from 72 PCa patients stained immunohistochemically for epithelial cell adhesion molecule (EpCAM), followed by validation in a cohort of 310 primary tumors from 209 PCa patients. In order to investigate the gene expression differences between tumors with low and high TSR, we applied multigene expression analysis (nCounter® PanCancer Progression Panel, NanoString) of 42 tissue samples. TSR scores were categorized into low (<1 TSR) and high (≥1 TSR). In the pilot cohort, 31 patients (43.1%) were categorized as low and 41 (56.9%) as high TSR score, whereas 48 (23.0%) patients from the validation cohort were classified as low TSR and 161 (77.0%) as high. In both cohorts, high TSR appeared to indicate the shorter time to biochemical recurrence in PCa patients (Log-rank test, p = 0.04 and p = 0.01 for the pilot and validation cohort, respectively). Additionally, in the multivariate analysis of the validation cohort, TSR predicted BR independent of other factors, i.e., pT, pN, and age (p = 0.04, HR 2.75, 95%CI 1.07-7.03). Our data revealed that tumors categorized into low and high TSR score show differential expression of various genes; the genes upregulated in tumors with low TSR score were mostly associated with extracellular matrix and cell adhesion regulation. Taken together, this study shows that high stroma content can play a protective role in PCa. Automatic EpCAM-based quantification of TSR might improve prognostication in personalized medicine for PCa.
| S-EPMC8622253 | biostudies-literature
Project description:BackgroundTumour microenvironment, including tumour-stroma ratio (TSR), might help identifying high-risk cancer patients. However, the significance of TSR in gastric cancer is unclear, especially in the intestinal and diffuse subtypes. The aim of this study was to investigate the tumour-stroma ratio in gastric adenocarcinoma, and its intestinal and diffuse histological subtypes, in relation to prognosis.MethodsFive hundred and eighty-three gastric adenocarcinoma patients who underwent surgery in Oulu University hospital during years 1983-2016 were included in this retrospective cohort study. TSR was analysed from the slides that were originally used for diagnostic purposes. Patients were divided into stroma-poor (≤50% stroma) and stroma-rich (>50% stroma) groups and TSR was analysed in relation to 5-year mortality and overall mortality.ResultsPatients with stroma-rich tumours had worse 5-year prognosis (HR 1.80, 95% CI 1.41-2.28) compared to stroma-poor tumours. Stratified analysis showed that stroma-rich tumours had worse 5-year prognosis in both intestinal (HR 1.68, 95% CI 1.24-2.27) and diffuse histological types (HR 2.09, 95% CI 1.35-3.23) compared to stroma-poor tumours, respectively.ConclusionsHigh proportion of stroma is an independent prognostic factor in both intestinal and diffuse histological subtypes of gastric adenocarcinoma.
| S-EPMC6133938 | biostudies-literature
Project description:OBJECTIVE:To correlate the tumor-stromal ratio (TSR) of invasive breast cancer and MRI findings. METHODS:This study was approved by our institutional review board. 126 consecutive patients with surgically proven invasive breast cancer were included. All patients underwent MRI exams including short-tau inversion-recovery (STIR) T 2 weighted imaging, diffusion-weighted imaging (DWI) and post-contrast dynamic imaging. The mean signal intensity (SI) and apparent diffusion coefficient (ADC) value of each lesion were measured. To objectively evaluate the STIR images, the ratio of the SI of the lesion to the muscle (L/M ratio) was also measured. Percentages of MRI kinetic parameters obtained from dynamic images were also measured. The TSR was defined as the percentage of the stromal component, and categorized into high-stroma (> 50%) and low-stroma (< 50%) groups. Intergroup differences in the SI, L/M ratio, ADC value and percentages of kinetic parameters were examined. RESULTS:The SI and L/M ratio of the high-stroma group were significantly lower than those of the low-stromal group (208.64 vs 331.86 for SI, 5.69 vs 9.31 for L/M ratio) (p < 0.001). The high-stroma group had significantly lower percentages of a washout pattern (25% vs 34.7 %) (p = 0.012) and significantly higher percentages of a persistent pattern (36.92% vs 28.26 %) (p = 0.044). There were no significant correlations between the TSR and ADC value. CONCLUSION:STIR and dynamic sequence of breast MRI reflects the stromal component of invasive breast cancer. ADVANCES IN KNOWLEDGE:This is the first study to correlate TSR and MRI findings. STIR and post-contrast dynamic study correlated with the stromal component of breast cancer.
| S-EPMC6580921 | biostudies-literature
Project description:It has been hypothesized that the net expression of a gene is determined by the combined effects of various transcriptional system regulators (TSRs). However, characterizing the complexity of regulation of the transcriptome is a major challenge. Principal component analysis on 17,550 heterogeneous human microarray experiments revealed that 50 orthogonal factors (hereafter called TSRs) are able to capture 64% of the variability in expression in a wide range of experimental conditions and tissues. We identified gene clusters controlled in the same direction and show that gene expression can be conceptualized as a process influenced by a fairly limited set of TSRs. Furthermore, TSRs can be linked to biological functions, as we demonstrate a strong relation between TSR-related gene clusters and biological functionality as well as cellular localization, i.e. gene products of similarly regulated genes by a specific TSR are located in identical parts of a cell. Using 3,934 diverse mouse microarray experiments we found striking similarities in transcriptional system regulation between human and mouse. Our results give biological insights into regulation of the cellular transcriptome and provide a tool to characterize expression profiles with highly reliable TSRs instead of thousands of individual genes, leading to a >500-fold reduction of complexity with just 50 TSRs. This might open new avenues for those performing gene expression profiling studies.
| S-EPMC2250855 | biostudies-literature
Project description:BackgroundSMAD family member 4 (SMAD4) has gained attention as a promising prognostic factor of colorectal cancer (CRC) as well as a key molecule to understand the tumorigenesis and progression of CRC.MethodsWe retrospectively analyzed 1,281 CRC cases immunohistochemically for their expression status of SMAD4, and correlated this status with clinicopathologic and molecular features of CRCs.ResultsA loss of nuclear SMAD4 was significantly associated with frequent lymphovascular and perineural invasion, tumor budding, fewer tumor-infiltrating lymphocytes, higher pT and pN category, and frequent distant metastasis. In contrast, tumors overexpressing SMAD4 showed a significant association with sporadic microsatellite instability. After adjustment for TNM stage, tumor differentiation, adjuvant chemotherapy, and lymphovascular invasion, the loss of SMAD4 was found to be an independent prognostic factor for worse 5-year progression-free survival (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.01 to 1.60; p=.042) and 7-year cancerspecific survival (HR, 1.45; 95% CI, 1.06 to 1.99; p=.022).ConclusionsWe confirmed the value of determining the loss of SMAD4 immunohistochemically as an independent prognostic factor for CRC in general. In addition, we identified some histologic and molecular features that might be clues to elucidate the role of SMAD4 in colorectal tumorigenesis and progression.
| S-EPMC6755646 | biostudies-literature