An absolute human stemness index associated with oncogenic dedifferentiation

Author(s):  
Hailong Zheng ◽  
Kai Song ◽  
Yelin Fu ◽  
Tianyi You ◽  
Jing Yang ◽  
...  

Abstract The progression of cancer is accompanied by the acquisition of stemness features. Many stemness evaluation methods based on transcriptional profiles have been presented to reveal the relationship between stemness and cancer. However, instead of absolute stemness index values—the values with certain range—these methods gave the values without range, which makes them unable to intuitively evaluate the stemness. Besides, these indices were based on the absolute expression values of genes, which were found to be seriously influenced by batch effects and the composition of samples in the dataset. Recently, we have showed that the signatures based on the relative expression orderings (REOs) of gene pairs within a sample were highly robust against these factors, which makes that the REO-based signatures have been stably applied in the evaluations of the continuous scores with certain range. Here, we provided an absolute REO-based stemness index to evaluate the stemness. We found that this stemness index had higher correlation with the culture time of the differentiated stem cells than the previous stemness index. When applied to the cancer and normal tissue samples, the stemness index showed its significant difference between cancers and normal tissues and its ability to reveal the intratumor heterogeneity at stemness level. Importantly, higher stemness index was associated with poorer prognosis and greater oncogenic dedifferentiation reflected by histological grade. All results showed the capability of the REO-based stemness index to assist the assignment of tumor grade and its potential therapeutic and diagnostic implications.

2020 ◽  
Vol 56 (1) ◽  
pp. 36-44
Author(s):  
Barbara Sabrine Franjić ◽  
Iva Milić Vranješ ◽  
Jakov Milić ◽  
Milanka Mrčela

Objectives: To determine the compatibility rate between histological grades of endometrial carcinoma in curettage and hysterectomy and to determine how quantity of material, given by the method of fractional hysterectomy, affects the compatibility between histological grades in the two methods. Material and methods: The study included 102 patients with endometrioid endometrial cancer who underwent methods of fractional curettage and hysterectomy. Data regardingthepathohistological status of uterine tissue was obtained from the available medical records. Information on age andclinical diagnoses were obtained from referrals for pathohistologicaltissue examination. The age of the subjects was determined at the time when the tissue samples were taken for analysis. Data on the amount of material was obtained from the description of macroscopic evaluation of the given material. Results: Most subjects had grade II endometrioid endometrial cancer (47.1 % and 50 %). Most of the respondents had a medium deficient material obtained by fractional curettage (40.2 %). There was no statistically significant difference between the histological grade determined after the fractional curettage and hysterectomy. There were no statistically significant differences in histological grade in the sample obtained by fractional curettage and hysterectomy depending on the amount of material in fractional curettage. Conclusions: There was no statistically significant differences in the grade of endometrial cancer in samples obtained by the fractional curettage and hysterectomy. The correspondence is higher in higher tumor grade (III), and lower in lower tumor grades (I, II). The amount of material did not affect the grade deviation in the sample obtained by fractional curettage and hysterectomy.


2019 ◽  
Author(s):  
Qian Liu ◽  
Xiaohong Li ◽  
Song Qin

Abstract Background This study aimed to investigate the biological characteristics of PHAP1 and SUMO2 in CSCC and the relationship between the expression of the 2 genes and HPV16 infection. Method To detect the function of PHAP1 and SUMO2 in the occurrence and development of CSCC, we first compared their expression patterns in CSCC tissue samples, CIN and matched normal tissues through IHC, and RT-PCR. In addition, we carried on WB assay to test the expression of PHAP1 and SUMO2 in the SiHa, C33A and Ect1 cell lines. We analyzed the relationship between the expression of PHAP1 and SUMO2 and HPV16 infection. Result The results demonstrated that PHAP1 and SUMO2 expression at both the protein and mRNA levels was elevated in CSCC tissues compared with CIN and normal tissues. The expression of SUMO2 was significantly associated with lymph node metastasis (P=0.02), AJCC stage(p=0.024), but not other clinicopathological factors. The expression of PHAP1 and SUMO2 protein in SiHa, C33A cells was obviously higher than that in Ect1 cells. The expression of PHAP1 and SUMO2 was associated with a susceptibility to HPV16 infections. Conclusion Our results imply that PHAP1 and SUMO2 may be potential tumor promoter genes and may provide the biological basis for diagnosis, prognosis and treatment for CSCC.


2019 ◽  
Vol 19 (11) ◽  
pp. 1359-1367 ◽  
Author(s):  
Xinyu Shao ◽  
Zhengwu Cheng ◽  
Menglin Xu ◽  
Jiading Mao ◽  
Junfeng Wang ◽  
...  

Background:Gastric Cancer (GC) is a frequently common malignancy. Recent studies have reported Rab1A as an activator of mTORC1, and the mTOR1 pathway is involved in regulating Gli1 expression in several cancers. Only a few studies have been performed to explore the relationship between Rab1A and p-S6K/Gli1in GC.Methods:Immunohistochemistry (IHC) was performed to explore the association of Rab1A/p-S6K/Gli1 expression and prognosis in 117 GC tissue samples and adjacent normal tissues.Results:Our results indicated that Rab1A/p-S6K/Gli1 was significantly overexpressed in GC tissues. High expression of Rab1A was closely related to the tumor size and the depth of tumor invasion. In addition, Rab1A expression was closely related with p-S6K/Gli1 expression in GC, and high level of Rab1A/p-S6K/Gli1 caused worse prognosis of GC patients. The univariate and multivariate analysis indicated that the expression of Rab1A was an independent prognostic factor. Moreover, both high Rab1A and p-S6K expression led to a worse prognosis when compared to a single positive expression as well as both high Rab1A/Gli1 expression also led to a worse prognosis than the single positive expression of Rab1A/Gli1. Strikingly, the overexpression of p-S6K also led to a worse prognosis in Rab1A positive patients, as did Gli1.Conclusion:Our results indicate that Rab1A/mTOR/S6K/Gli1 axis played a crucial role in GC, which may provide a novel field on targeted therapy of GC, especially for mTORC1-targeted therapy-resistant cancers.


2006 ◽  
Vol 53 (2) ◽  
pp. 57-60
Author(s):  
Eva Langner ◽  
Karolina Przybyzowska ◽  
Galbfach Przemyszaw ◽  
Janusz Kunierz ◽  
Beata Smolarz ◽  
...  

The DNA mismatch repair (MMR) system guards against genomic instability, therefore the mutations in the human MMR genes cause the majority of the hereditary nonpolyposis colorectal cancer (HNPCC) and a small percentage of the sporadic colon cancer. hMSH2 is one of MMR genes involved in the correction of mispairing during replication and its mutations are associated with both - microsatellite instability and the hereditary and sporadic colon tumor genesis. The aim of this study was to analyze the T/G mutation (codon 458) in exon 8 of hMSH2 gene in the sporadic colon cancer cells. We also examined the relationship between the T/G mutation of hMSH2 gene, and the selected prognostic factors such as Dukes? stage, histological grade and lymph node metastasis. We analyzed samples of tumor from 75 patients with sporadic colorectal cancers. The mutation in the hMSH2 gene ware determined by the RFLP-PCR. We found T/G mutation in exon 8 of hMSH2 gene in 5 patients (6,7%). There was no statistically significant difference between this mutation and selected clinical parameters. The results of our studies revealed that mutations of hMSH2 gene may lead to development of colorectal cancer. No dependence between the mutation of hMSH2 gene and clinical parameters, suggests that the mutation of hMSH2 gene may have a critical significance for the first steps of carcinogenesis in colon epithelial.


2021 ◽  
Vol 19 (8) ◽  
pp. 20-26
Author(s):  
Zeena Ayad Khalid ◽  
Sazan Abdulwahab Mirza ◽  
Azza Nazar Dhannoon

Background: meningioma is considered a common benign tumor and more frequent happen, they are slow growing primary tumors that originate from meningothelial cells of the arachnoid and spinal cord. The histological grade of the WHO and the extension of the initial surgical resection are determining prognostic factors in these tumors. Aim of the study: To investigate the expression of EGFR and ErbB2 / HER2 in human meningiomas, to correlate this expression with various clinic pathological parameters (age, gender, tumor type, tumor grade), and to study the correlation between these two markers. Methods: this is a retrospective study including 30 cases of human meningiomas. Clinical data collected from patient's files. Immunohistochemical study of EGFR and ErbB2/HER2 performed along with scoring. Results: this study included 30 cases of meningioma. There was a significant statistical correlation between tumor grade and tumor histological type, as 100% of grade II were atypical meningiomas, and 77.8% of grade I were meningiothelial meningiomas, with a P value 0.0001. 25/30 cases showed positive immunohistochemical expression of EGFR, 24/25 (96%) cases were grade I, 1/25 (4%), 16/25(72%) cases were meningiothelial, 1/25 (4%) case angiomatous, 1/25 (4%) case atypical, 5/25 (20%) cases were fibroblastic. only 4/30 cases showed expression of HER 2/ neu, 3/4(75%) cases were female, all cases were above 30 years of age, all cases were grade I, 2/4 (50%) cases were fibroblastic and the other two cases were meningiothelial type. Conclusions: EGFR is frequently over expressed in meningiomas, there was a significant difference between mean of EGFR and HER 2, EGFR have more positive results than HER 2.


2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Feng CD ◽  
◽  
Zhang Y ◽  
Xu ZP ◽  
Gao BY ◽  
...  

Background: Intrinsic molecular subtype and histological grade are closely related to clinical prognosis in breast cancer. However, their relationship with Programmed Cell Death-Ligand 1 (PD-L1) expression is not very clear, particularly for Hainan Aboriginal patients. Herein, this research aims to reveal the relationship between PD-L1 expression and intrinsic molecular subtypes of breast cancer. Methods: 225 breast tumor samples from female patients were analyzed for PD-L1 expression using the Immunohistochemistry (IHC) method. The PDL1 expression level was detected by IHC and the relationship between the expression and clinical parameters was analyzed statistically. Results: Positive staining of PD-L1 was mainly found in the plasma membrane. In all cases, the positive rate was 12.0% (27/225). The PD-L1 expression level was significantly reduced in Luminal A subtype (the corrected ratio OR=0.15, p=0.04) whereas increased in HER2-positive subtype (OR=4.2, p=0.01). PD-L1 was significantly related to HER2-positive subtype (p<0.05) and histological grade 3 (p<0.05). There was statistically significant association between PD-L1 expression and metastasis (p=0.046), but not with the patient’s age, the tumor stage and menstruation (p>0.05). Moreover, there was a significant difference in the frequency of intrinsic subtypes between patients with positive and negative PD-L1 expression (p<0.001) among patients with metastasis. Conclusions: PD-L1 expression in breast cancer was positively correlated with HER2-positive subtype, higher pathological grade and metastasis of breast cancer, while negatively correlated with Luminal A in female patients in Hainan, China. PD-L1 may be a new independent marker to predict the prognostic factor in HER2-positive subtype breast cancer.


2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Maryam Alamdar ◽  
Majid Sadeghizadeh

Background: Colorectal cancer (CRC) is the second and third most common cancer in men and women respectively, and the fourth cause of cancer death of individuals. Mutations in specific genes can lead to colorectal cancer. UCA1 is one of the oncogenic genes that have been shown to stimulate cell proliferation. mTOR1 is another gene that leads to the growth of cancer cells through anabolic processes and autophagy inhibition. Objectives: In this study, we evaluate the expression of these two genes in different phases of CRC, that helps the early detection of colorectal cancer which can increase the survival rate. Methods: First, we collected 25 colorectal cancer tumor tissues and 25 adjacent normal tissues as a control group. Then, RNA was extracted from tissue samples and cDNA synthesized. The UCA1 and mTOR1 expression was evaluated in CRC tissues compared to adjacent normal tissues by Real Time PCR. Results: Our results showed that the UCA1 and mTOR1 expression in the tumor tissues was significantly higher than in the adjacent normal tissues (P < 0.05). There was also a significant difference in Lynph inv and Vescu inv with mTOR1 expression (P < 0.05). Conclusions: Our results showed that UCA1/mTOR1 may be important genes involved in colorectal cancer. mTOR1 was also identified as one of the possible genes in metastasis of colorectal cancer. Thus, UCA1 and mTOR1 can probably be considered as biomarkers in CRC therapy and diagnosis.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jinmin Zhao ◽  
Hua Xu ◽  
Maolin He ◽  
Zhe Wang ◽  
Yang Wu

The Rho GTPase-activating protein 35 (ARHGAP35), an important Rho family GTPase-activating protein, may be associated with tumorigenesis of some tumors. Here, we investigated the relationship between an important polymorphic variant at 3′-UTR of this gene (rs1052667) and osteosarcoma risk and prognosis. This hospital-based case-control study, including 247 osteosarcoma patients and 428 age-, sex-, and race-matched healthy controls, was conducted in Guangxi population. Genotypes were tested using TaqMan PCR technique. We found a significant difference in the frequency of rs1052667 genotypes between cases and controls. Compared with the homozygote of rs1052667 C alleles (rs1052667-CC), the genotypes with rs1052667 T alleles (namely, rs1052667-CT or -TT) increased osteosarcoma risk (odds ratios: 2.41 and 7.35, resp.). Moreover, rs1052667 polymorphism was correlated with such pathological features of osteosarcoma as tumor size, tumor grade, and tumor metastasis. Additionally, this polymorphism also modified the overall survival and recurrence-free survival of osteosarcoma cases. Like tumor grade, ARHGAP35 rs1052667 polymorphism was an independent prognostic factor influencing the survival of osteosarcoma. These results suggest that ARHGAP35 rs1052667 polymorphism may be associated with osteosarcoma risk and prognosis.


2000 ◽  
Vol 39 (01) ◽  
pp. 10-15 ◽  
Author(s):  
S. P. Müller ◽  
Ch. Reiners ◽  
A. Bockisch ◽  
Katja Brandt-Mainz

Summary Aim: Tumor scintigraphy with 201-TICI is an established diagnostic method in the follow-up of differentiated thyroid cancer. We investigated the relationship between thyroglobulin (Tg) level and tumor detectability. Subject and methods: We analyzed the scans of 122 patients (66 patients with proven tumor). The patient population was divided into groups with Tg above (N = 33) and below (N = 33) 5 ng/ml under TSH suppression or above (N = 33) and below (N = 33) 50 ng/ml under TSH stimulation. Tumor detectability was compared by ROC-analysis (True-Positive-Fraction test, specificity 90%). Results: There was no significant difference (sensitivity 75% versus 64%; p = 0.55) for patients above and below 5 ng/ml under TSH suppression and a just significant difference (sensitivity 80% versus 58%; p = 0.04) for patients above and below 50 ng/ml under TSH stimulation. In 18 patients from our sample with tumor, Tg under TSH suppression was negative, but 201-TICI-scan was able to detect tumor in 12 patients. Conclusion: Our results demonstrate only a moderate dependence of tumor detectability on Tg level, probably without significant clinical relevance. Even in patients with slight Tg elevation 201-TICI scintigraphy is justified.


Author(s):  
Ma. Dulce C. Guillena

Gonado-somatic index and fecundity are tools for measuring the sexual maturity and ability of animals to reproduce.  This study investigates the reproduction of Trichiurus lepturus. Specifically, this aimed to determine the sex ratio, the GSI, the relationship between fecundity and total length, fecundity and total weight, fecundity and ovary weight. The Descriptive Method of research was used.  Percentage and chi-square was utilized in determining the percentage of occurrence and sex ratio respectively.   Pearson r Product Moment Coefficient of Correlation was used to determine the relationships of the parameters. The study revealed that females outnumbered males and the sex ratio for different month showed significant difference.  Spawning season was observed to occur in November and December as revealed in its GSI values and it synchronized with the full and new moon phases.  Fecundity is positively correlated with body weight, body size, and ovary weight where ovary weight is observed to be the best index for fecundity.  The results of this study could be used further for formal stock assessment of cutlassfish fishery.


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