MicroRNA-216a targets WT1 expression and regulates KRT7 transcription to mediate the progression of pancreatic cancer-A transcriptome analysis.

Gene expression profiling has been broadly performed in the field of cancer research. This study aims to explore the key gene regulatory network and focuses on the functions of microRNA (miR)-216a in pancreatic cancer (PC). PC datasets GSE15471, GSE16515, and GSE32676 were used to screen the differentially expressed genes (DEGs) in PC. A miRNA microarray analysis and gene oncology analysis suggested miR-216a as an important differentially expressed miRNA in PC. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that miR-216a and the DEGs are largely enriched on the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. miR-216a targeted Wilms Tumor 1 (WT1), while WT1 promoted transcription activity of keratin 7 (KRT7). Upregulation of miR-216a reduced proliferation and invasiveness of PC cells, while further upregulation of WT1 blocked the functions of miR-216a. Silencing of KRT7 diminished the oncogenic role of WT1. The in vitro results were reproduced in vivo. High expression of miR-216a while poor expression of WT1 indicated better prognosis of PC patients. The miR-216a/WT1/KRT7 axis influenced the activity of the PI3K/AKT pathway. To conclude, this study evidenced that miR-216a suppressed WT1 expression and blocked KRT7 transcription, which inactivated the PI3K/AKT signaling and reduced PC progression.

Reactivity of CK7 across the spectrum of renal cell carcinomas with clear cells.

AIMS: Current available data on cytokeratin 7 (CK7) immunostaining pattern in the clear cell renal cell carcinoma (RCC) spectrum is conflicting. The aim of this study was to assess CK7 immunoreactivity within the spectrum of clear cell renal neoplasms, including clear cell RCC, multicystic renal neoplasm of low malignant potential and clear cell papillary RCC-like tumours. METHODS AND RESULTS: We analysed two clones of CK7 and two tumour blocks for a total of 75 cases divided into five distinct groups: (i) low-grade clear cell RCC, (ii) high-grade clear cell RCC, (iii) multicystic renal neoplasm of low malignant potential, (iv) clear cell RCC with cystic changes and (v) clear cell papillary RCC-like tumours. We found the highest CK7 reactivity in low-grade clear cell RCC, multicystic renal neoplasm of low malignant potential and clear cell papillary RCC-like groups, ranging from 60% to 93%. CONCLUSIONS: Our findings show that CK7 immunoreactivity in clear cell RCC is variable, and the extent of staining depends on the grade and architectural growth patterns of the tumours.

Low-grade oncocytic tumour of kidney (CD117-negative, cytokeratin 7-positive): a distinct entity?

AIM: To describe a group of distinct low-grade oncocytic renal tumours that demonstrate CD117 negative/cytokeratin (CK) 7-positive immunoprofile. METHODS AND RESULTS: We identified 28 such tumours from four large renal tumour archives. We performed immunohistochemistry for: CK7, CD117, PAX8, CD10, AMACR, e-cadherin, CK20, CA9, AE1/AE3, vimentin, BerEP4, MOC31, CK5/6, p63, HMB45, melan A, CD15 and FH. In 14 cases we performed array CGH, with a successful result in nine cases. Median patient age was 66 years (range 49-78 years) with a male-to-female ratio of 1:1.8. Median tumour size was 3 cm (range 1.1-13.5 cm). All were single tumours, solid and tan-brown, without a syndromic association. On microscopy, all cases showed solid and compact nested growth. There were frequent areas of oedematous stroma with loosely arranged cells. The tumour cells had oncocytic cytoplasm with uniformly round to oval nuclei, but without significant irregularities, and showed only focal perinuclear halos. Negative CD117 and positive CK7 reactivity were present in all cases (in two cases there was focal and very weak CD117 reactivity). Uniform reactivity was found for PAX8, AE1/AE3, e-cadherin, BerEP4 and MOC31. Negative stains included CA9, CK20, vimentin, CK5/6, p63, HMB45, Melan A and CD15. CD10 and AMACR were either negative or focally positive; FH was retained. On array CGH, there were frequent deletions at 19p13.3 (seven of nine), 1p36.33 (five of nine) and 19q13.11 (four of nine); disomic status was found in two of nine cases. On follow-up (mean 31.8 months, range 1-118), all patients were alive with no disease progression. CONCLUSION: Low-grade oncocytic tumours that are CD117-negative/CK7-positive demonstrate consistent and readily recognisable morphology, immunoprofile and indolent behaviour.

p16ink4 and cytokeratin 7 immunostaining in predicting HSIL outcome for low-grade squamous intraepithelial lesions: a case series, literature review and commentary.

p16ink4 and cytokeratin 7 (CK7) have been proposed to identify low-grade squamous intraepithelial lesions (LSIL) at greater or lesser risk for an outcome of high-grade squamous intraepithelial lesion (HSIL). We correlated CK7 and p16ink4 staining in LSILs with outcome on follow-up and placed this information in the context of prior reports. Cervical LSIL biopsies with at least 1-year follow-up information were immunostained for CK7 and p16ink4. Follow-up outcomes included no SIL, LSIL (persistence) or HSIL (CIN2+). In all, 109 LSILs were studied and 18.3% stained positive for CK7. Ninety-one percent of CK7-negative LSILs regressed, 4.5% persisted, and 4.5% had an HSIL outcome, versus 60, 20, and 20% of CK7-positive LSILs, respectively (P=0.036). p16ink4 status did not significantly associate with outcome. Review of the literature revealed a highly variable rate of both positive p16ink4 immunoreactivity in LSIL and CIN2+ outcome for p16-positive LSIL but a consistently high negative predictive value (>90%) in the case of no/low p16 expression. Inter-observer reproducibility for the diagnosis of CIN2 in the literature ranged from poor to good, with unanimous agreement on the diagnosis of CIN2 occurring in less than 25% of cases. As with high-risk human papillomavirus testing, the most clinically useful result of p16ink4 staining is a negative test, implying no lesion or CIN1 and conferring a low risk of HSIL outcome. HSIL outcomes ('progression') are highly variable and are subject to wide differences in inter-observer interpretation for CIN2. This argues against the wisdom of relying on p16ink4 to both predict CIN2+ or upgrade CIN1 to CIN2. It also begs the question of whether CIN2 should be replaced by an alternate and less pejorative term (SIL of intermediate grade) for lesions that are not reproducibly classified as LSIL or HSIL, with an appropriate management scheme.

Complete and unidirectional conversion of human embryonic stem cells to trophoblast by BMP4.

Human ES cells (hESC) exposed to bone morphogenic protein 4 (BMP4) in the absence of FGF2 have become widely used for studying trophoblast development, but the soundness of this model has been challenged by others, who concluded that differentiation was primarily toward mesoderm rather than trophoblast. Here we confirm that hESC grown under the standard conditions on a medium conditioned by mouse embryonic fibroblasts in the presence of BMP4 and absence of FGF2 on a Matrigel substratum rapidly convert to an epithelium that is largely KRT7(+) within 48 h, with minimal expression of mesoderm markers, including T (Brachyury). Instead, they begin to express a series of trophoblast markers, including HLA-G, demonstrate invasive properties that are independent of the continued presence of BMP4 in the medium, and, over time, produce extensive amounts of human chorionic gonadotropin, progesterone, placental growth factor, and placental lactogen. This process of differentiation is not dependent on conditioning of the medium by mouse embryonic fibroblasts and is accelerated in the presence of inhibitors of Activin and FGF2 signaling, which at day 2 provide colonies that are entirely KRT7(+) and in which the majority of cells are transiently CDX2(+). Colonies grown on two chemically defined media, including the one in which BMP4 was reported to drive mesoderm formation, also differentiate at least partially to trophoblast in response to BMP4. The experiments demonstrate that the in vitro BMP4/hESC model is valid for studying the emergence and differentiation of trophoblasts.

Aberrant keratin 7 and 20 expression in triple-negative carcinoma of the breast.

Early studies characterizing the keratin (K) profile of various epithelial tissues indicated that breast carcinoma is K7 positive and K20 negative, but not all breast carcinomas show this profile. Triple-negative carcinoma (TNC) has been characterized by negativity for estrogen receptor (ER), progesterone receptor (PgR), and Her2/neu protein. TNC is more likely to metastasize to the viscera and present as a metastatic poorly different carcinoma. In our study, on the basis of immunohistochemical staining of ER, PgR, and Her2/neu, 75 of the 290 patients with invasive breast carcinoma were judged to have TNC. K20 expression was detected in 6 of 75 patients with TNC, and non-TNC was negative in all 215 cases (P = .0003). K7 expression was also detected in 72 of 75 TNC cases. However, non-TNC was negative in 26 of 215 cases, which was significant (P = .0457). An aberrant profile of K was observed in the TNC group, indicating that caution is needed in determining the site of primary tumors using immunohistochemical algorithms. It should be kept in mind that patients with TNC show highly variable K profiles in practical diagnosis.

Keratin 7 expression in lymph node metastases but not in the primary tumour correlates with distant metastases and poor prognosis in colon carcinoma.

Colorectal carcinoma (CRC) is one of the leading causes of cancer-related deaths worldwide. Alterations in keratin expression, including keratin 7 (K7), are frequent findings in multiple cancers, and they constitute a prognostic factor. The aim of our study was to evaluate the prognostic significance of K7 in the primary tumour and lymph node metastases in two separate cohorts of patients: the first one with lymph node involvement (LN+, 129 cases) and the second one free of LN metastases (LN-, 85 cases). Keratin 7 expression in CRC was analysed on tissue microarrays with immunohistochemistry and evaluated using the h-score. In the LN+ group K7 positivity was identified in 7/129 (5.4%) of primary tumours (PT) and lymph node metastases (LNM); concordance between them was 94% ( 0.396). Keratin 7 was expressed in 8/85 cases (9.4%) in the LN- group. K7 expression in LNM of the LN+ cohort correlated with shorter overall survival (OS) (p = 0.047) and presence of distant metastases at diagnosis (p = 0.005). Expression of K7 in the primary tumour in both cohorts did not correlate with survival. We conclude that the status of K7 expression in metastatic lymph nodes from CRC is a poor prognostic factor.

Primary perianal Paget's disease with focal adenocarcinoma, signet-ring cell differentiation and unusual immunohistochemical expression: a case report.

Perianal Paget's disease is an uncommon intraepidermal carcinoma characterized by the presence ofPaget cells. It usually affects older patients and commonly presents as chronic perianal pruritus with scaly plaques. The disease is categorized into primary perianal Paget's disease ofcutaneous origin and secondaryperianal Paget's disease, which is due to extension of a visceral malignancy such as that of the anorectum or colon. Cytokeratin 7 (CK7), cytokeratin 20 (CK20), and gross cystic disease fluid protein-15 (GCDFP15) expression are useful for differentiation between these two types. A tumor immunohistochemical profile of CK7+/CK20-/GCDFP15+ suggests the primary type, whereas CK7+/CK20+/GCDFP15- suggests the secondary type. The expression of caudal homeobox 2 (CDX2) suggests the secondary type from anorectal or colonic adenocarcinoma. However, approximately one- third of patients without visceral malignancy have a tumor that is CK7+/CK20+/GCDFP15-. Two percents of primary perianal Paget ' disease can express CDX2. The author reports a case ofan 86-year-old man who presented with chronic perianalpruritus and a scaly plaque. A skin biopsy showed intraepidermal Paget cells with immunohistochemical profile of CK7+/CK20+/GCDFPJ5-/CDX2+. Initially, secondary perianal Paget's disease from colorectal adenocarcinoma was suspected. However, extensive investiga- tions found no visceral malignancy. The patient underwent wide excision of the perianal skin. Pathological examination showed diffuse intraepidermal Paget cells withfocal dermal invasion by intestinal-type adenocarcinoma and signet-ring cell differentiation. In conclusion, thefinal diagnosis was primary perianal Paget's disease withfocal adenocarcinona and signet- ring cell differentiation. The disease was consistent with primary perianal Paget's disease, because no visceral malignancy was found.

Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse.

Early mammalian embryogenesis is controlled by mechanisms governing the balance between pluripotency and differentiation. The expression of early lineage-specific genes can vary significantly between species, with implications for developmental control and stem cell derivation. However, the mechanisms involved in patterning the human embryo are still unclear. We analyzed the appearance and localization of lineage-specific transcription factors in staged preimplantation human embryos from the zygote until the blastocyst. We observed that the pluripotency-associated transcription factor OCT4 was initially expressed in 8-cell embryos at 3 days post-fertilization (dpf), and restricted to the inner cell mass (ICM) in 128-256 cell blastocysts (6dpf), approximately 2 days later than the mouse. The trophectoderm (TE)-associated transcription factor CDX2 was upregulated in 5dpf blastocysts and initially coincident with OCT4, indicating a lag in CDX2 initiation in the TE lineage, relative to the mouse. Once established, the TE expressed intracellular and cell-surface proteins cytokeratin-7 (CK7) and fibroblast growth factor receptor-1 (FGFR1), which are thought to be specific to post-implantation human trophoblast progenitor cells. The primitive endoderm (PE)-associated transcription factor SOX17 was initially heterogeneously expressed in the ICM where it co-localized with a sub-set of OCT4 expressing cells at 4-5dpf. SOX17 was progressively restricted to the PE adjacent to the blastocoel cavity together with the transcription factor GATA6 by 6dpf. We observed low levels of Laminin expression in the human PE, though this basement membrane component is thought to play an important role in mouse PE cell sorting, suggesting divergence in differentiation mechanisms between species. Additionally, while stem cell lines representing the three distinct cell types that comprise a mouse blastocyst have been established, the identity of cell types that emerge during early human embryonic stem cell derivation is unclear. We observed that derivation from plating intact human blastocysts resulted predominantly in the outgrowth of TE-like cells, which impairs human embryonic stem cell derivation. Altogether, our findings provide important insight into developmental patterning of preimplantation human embryos with potential consequences for stem cell derivation.

Cell turnover in the repopulated rat liver: distinct lineages for hepatocytes and the biliary epithelium.

The dynamics of cell renewal in the normal adult liver remains an unresolved issue. We investigate the possible contribution of a common biliary precursor cell pool to hepatocyte turnover in the chimeric long-term repopulated rat liver. The retrorsine (RS)-based model of massive liver repopulation was used. Animals not expressing the CD26 marker (CD26(-)) were injected with RS, followed by transplantation of 2 million syngeneic hepatocytes isolated from a normal CD26-expressing donor. Extensive (80-90%) replacement of resident parenchymal cells was observed at 1 year post-transplantation and persisted at 2 years, as expected. A panel of specific markers, including cytokeratin 7, OV6, EpCAM, claudin 7 and α-fetoprotein, was employed to locate the in situ putative progenitor and/or biliary epithelial cells in the stably repopulated liver. No overlap was observed between any of these markers and the CD26 tag identifying transplanted cells. Exposure to RS was not inhibitory to the putative progenitor and/or biliary epithelial cells, nor did we observe any evidence of cell fusion between these cells and the transplanted cell population. Given the long-term (>2 years) stability of the donor cell phenotype in this model of liver repopulation, the present findings suggest that hepatocyte turnover in the repopulated liver is fuelled by a cell lineage distinct from that of the biliary epithelium and relies largely on the differentiated parenchymal cell population. These results support the solid biological foundation of liver repopulation strategies based on the transplantation of isolated hepatocytes.

Expression of CK7, Cam 5.2 and Ber-Ep4 in cutaneous squamous cell carcinoma.

BACKGROUND: Cytokeratin 7 (CK7) and Cam 5.2 are often used to differentiate extramammary Paget's disease (EPD) from squamous cell carcinoma (SCC) in situ because they are generally considered to be expressed in the former but not in the latter. However, we have encountered CK7+ and Cam 5.2+ SCCs. METHODS: We evaluated CK7, Cam 5.2 and Ber-Ep4 expression in SCC and EPD. RESULTS: We found significant CK7 and Cam 5.2 positivity in SCCs, particularly in those with a pagetoid pattern. Only one case expressed Ber-Ep4. CONCLUSIONS: We conclude that CK7 and Cam 5.2 expression may occur in SCC. A panel including Ber-Ep4 is advisable for immunohistochemical differentiation of EPD from SCC.

Source of angiopoietin-2 in the sera of women during pregnancy.

Placental development requires coordinated angiogenesis regulated by multiple factors including angiopoietins. Previously we demonstrated that the concentration of angiopoietin-2 (Ang-2) in the sera of women rises markedly in pregnancy in early gestation. This increase is reduced in pregnancies subsequently complicated by intrauterine growth restriction (IUGR). We now show that the concentration of Ang-2, but not Ang-1, in maternal serum is increased during normal pregnancy, peaking at the end of the first trimester. We also demonstrate that a key source of the elevated Ang-2 levels during pregnancy is decidual endothelial cells (DECs) but not cytotrophoblasts. Secretion of Ang-2 by DECs relies on the release from intracellular stores and the synthesis of new Ang-2 protein and is regulated by serum factors at a translational level. Further studies on the role of Ang-2 during pregnancy are warranted as well as the evaluation of Ang-2 as a marker to predict adverse pregnancy outcomes.

Cytokeratin 7: a re-evaluation of the 'tried and true' in triple-negative breast cancers.

AIMS: Triple-negative breast cancers (TNBCs) are often poorly differentiated tumours that can present clinically as metastases of an unknown primary. Immunohistochemical panels are frequently used to determine the likelihood of a breast primary, but in this tumour subset cytokeratin (CK)7 may be the only positive finding. In this study we aimed to evaluate a commonly employed immunohistochemical panel using a large group of TNBCs (both basal-like and unclassified), and to analyse the CK7 staining patterns. METHODS AND RESULTS: Tissue microarrays containing 138 TNBCs were stained with antibodies against CK7, CK20, gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin. CK5/6 staining was used to identify basal-like tumours. CK7 staining was notably heterogeneous, with 14.5% of all cases demonstrating ≤20% tumour cell staining. A greater proportion of basal-like TNBCs than of unclassified TNBCs showed focal staining. GCDFP-15 and mammaglobin were not expressed in the majority of TNBCs, and were less frequently positive in basal-like than in unclassified TNBCs. CONCLUSION: TNBCs are commonly negative for most immunomarkers indicative of breast origin, with the exception of CK7. As about one in five TNBCs showed only focal CK7 positivity, use of this marker must be interpreted with caution, especially in small samples, so that the possibility of a breast primary is not overlooked.

The Role of CK7, S100A1, and CD82 (KAI1) Expression in the Differential Diagnosis of Chromophobe Renal Cell Carcinoma and Renal Oncocytoma.

Renal oncocytoma is a benign renal tumor originated from intercalated cells of collecting ducts like chromophobe renal cell carcinoma (RCC). The differential diagnosis of these 2 tumors is important because while they are histologically and cytologically similar, they show different biological behavior. For the differential diagnosis, several immunohistochemical markers have been investigated. But, differential diagnostic challenges remain and the identification of additional markers is needed. Cytokeratin 7 (CK7) is one of ductal-type keratins, which is expressed in tumors of breast, pancreas, lung, thyroid, ovary, endometrium, urinary bladder, and the kidney. S100A1 is the first defined member of the calcium-binding S100 protein family and it organizes several cellular functions including cell cycle progression and cell differentiation.CD82 is a tetraspanin membrane protein, which functions as a metastasis supressor. In this study, we immunohistochemically investigated the expressions of CK7, S100A1, and CD82 in 30 chromophobe RCC (23 classic and 7 eosinophilic variant) and 19 oncocytomas. When these markers were evaluated separately and together, their expressions in chromophobe RCC and renal oncocytoma show statistically significant difference (P<0.001). Similar statistically significant results were also seen between eosinophilic chromophobe RCC and oncocytoma (P<0.001). For both classic and eosinophilic-variant chromophobe RCCs, CK7+/S100A1-/CD82+ profile being the most common. In oncocytomas, the most frequently observed profile was CK7-/S100A1+/CD82-. Our results showed that the application of a panel consisting of CK7, S100A1, and CD82 may provide accurate categorization of the tumors in difficult cases.

Aberrant expression of cytokeratin 7 in perivenular hepatocytes correlates with a cholestatic chemistry profile in patients with heart failure.

A cholestatic liver chemistry profile (elevations in alkaline phosphatase and bilirubin) is commonly encountered in patients with hepatic venous outflow obstruction due to right heart failure. Liver biopsies from these patients demonstrate varying degrees of sinusoidal dilatation, red blood cell extravasation and sinusoidal congestion. Recently, a bile ductular reaction mimicking biliary tract disease has been identified in ∼ 50% of patients with venous outflow obstruction possibly explaining the cholestatic profile encountered in these patients. In this study, we evaluated the liver biopsies from 22 patients with heart failure. Marked sinusoidal dilatation involving zones 2 and 3 was observed in 15 patients. Similar to a previous study, 7 of 22 patients had histologic evidence of a mild ductular reaction. Cytokeratin 7 immunohistochemistry revealed a mild ductular reaction in an additional two cases. Strikingly, CK7 was aberrantly expressed in perivenular hepatocytes in 20 of 22 cases. Perivenular CK7 immunoreactivity was focal in most cases; however, in five cases it was quite extensive and extended into zone 2. There was no significant association between marked sinusoidal dilatation and extensive perivenular CK7 positivity. Extensive perivenular CK7 positivity was significantly associated with both elevated bilirubin, as well as the presence of fibrosis. However, a ductular reaction was not associated with a cholestatic liver chemistry profile.

Significant high expression of cytokeratins 7, 8, 18, 19 in pulmonary large cell neuroendocrine carcinomas, compared to small cell lung carcinomas.

The aim of the present study was to clarify protein profiling in small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC). The proteomic approach was used, and involved cell lysate from two cell lines (N231 derived from SCLC and LCN1 derived from LCNEC), with 2-D gel electrophoresis (2-DE). In the present study, 25 protein spots with greater than twofold quantitative differences between LCN1 and N231 cells on 2-DE gels were confirmed. Within the 25 identified proteins, cytokeratins (CK) 7, 8, 18 and 19 were upregulated in LCN1 cells compared with N231 cells. The expression of CK7, 8, 18, and 19 was further studied on immunohistochemistry with 81 formalin-fixed and paraffin-embedded pulmonary carcinomas, which included 27 SCLC, 30 LCNEC, 14 adenocarcinomas, and 10 squamous cell carcinomas. Although the expression of CK7, 8, 18, and 19 was observed in all histological types, the mean immunostaining scores of CK7, 8, 18, and 19 were significantly higher in LCNEC than in SCLC (P < 0.001, P < 0.001, P < 0.01 and P < 0.001, respectively). These data suggest that the biological characteristics of LCNEC and SCLC may be different and the expression of CK may serve as differential diagnostic markers.

Adenosquamous carcinoma: a report of nine cases with p63 and cytokeratin 5/6 staining.

Adenosquamous carcinoma, a rare tumor of the skin with few reported cases in the literature, has not been studied with p63, cytokeratin 5/6 and cytokeratin 7. We stained nine such tumors with these markers. Histologically, the tumors showed superficial, atypical islands of keratinocytes in close association with islands displaying glandular differentiation. Clinically, lesions favored the head and trunk, and a subset of cases showed aggressive behavior. All tumors marked with p63 and cytokeratin 5/6, substantiating that diffuse positivity with these stains is supportive of a primary cutaneous origin. Six tumors stained focally in luminal areas with cytokeratin 7. Recognition of adenosquamous carcinoma is important for appropriate therapy, and stains for p63 and cytokeratin 5/6 may be helpful in ruling out metastatic adenocarcinoma.

High Proliferative Placenta-Derived Multipotent Cells Express Cytokeratin 7 at Low Level.

The purpose of this study was to investigate the immunophenotypes and gene expression profile of high proliferative placenta-derived multipotent cells (PDMCs) population at different stages of culture. We demonstrated that the colonies resulting from single cells were either positive or negative for CK7, whereas only PDMC clones with weak CK7 expression (CK7low-clones) were highly proliferative. Interestingly, vimentin positive (Vim+) placental stromal mesenchymal cells did not express CK7 in situ, but double CK7+Vim+ cells detection in tissue explants and explants outgrowth indicated CK7 inducible expression in vitro. PCNA presence in CK7+Vim+ cells during placental explants culturing confirmed belonging of these cells to proliferative subpopulation. Transcription factors CDX2 and EOMES were expressed in both CK7low-clones and subset of stromal mesenchymal cells of first-trimester placental tissue in situ. Meanwhile, CK7low -clones and stromal mesenchymal cells of full-term placental tissue in situ expressed ERG heterogeneously. SPP1, COL2A1, and PPARG2 mesodermal-related genes expression by CK7low-clones additionally confirms their mesenchymal origin. Inherent stem cell-related gene expression (IFTM3, POU5F1, and VASA) in CK7low-clones might indicate their enrichment for progenitors. Finally, in CK7low-clones we observed expression of such trophoblast-associated genes as CGB types I and II, fusogenic ERVW-1, GCM1, and GATA3. Thus, our results indicate that PDMCs acquired the representative immunophenotype signature under culture conditions.

Cytokeratin 7 and thyroid transcription factor - 1 levels in patients with lung cancer complicated with superior vena cava syndrome and their correlation with clinicopathological characteristics.

PURPOSE: This study aimed to detect the levels of cytokeratin 7 (CK7) and thyroid transcription factor -1(TTF-1) in serum of patients with non-small cell lung cancer (NSCLC) complicated with superior vena cava syndrome (SVCS), and to explore their prognosis and relationship and correlation with pathological characteristics. METHODS: 68 patients with non-small cell lung cancer (NSCLC) complicated with SVCS treated in Shaoxing Second Hospital from July 2014 to May 2018 were selected as the experimental group, 60 normal healthy persons as the control group, and 60 patients with lung cancer as the lung cancer group. The levels of CK7 and TTF-1 in the three groups were determined by enzyme-linked immunosorbent assay (ELISA), and the differences were compared. The relationship between the expression levels of CK7 and TTF-1 and clinicopathological characteristics of patients, the correlation between CK7 and TTF-1 in lung cancer patients complicated with SVCS, and their 3-year survival rate were analyzed. RESULTS: CK7 and TTF-1 levels in experimental group were significantly higher than those in control group (P<0.05). The levels in lung cancer group were significantly higher than those in control group (P<0.05). In experimental group, the expression of CK7 and TTF-1 was not related to gender, age, weight, histological classification and tumor size (P>0.05)). CK7 expression was positively correlated with TTF-1 expression in lung cancer patients (P<0.001). The 3-year survival rate in CK7 and TTF-1 high expression group was significantly lower than that in low expression group (P<0.05). CONCLUSION: The expressions of CK7 and TTF-1 are increased in patients with lung cancer complicated with SVCS, and are related to TNM stage, lymph node metastasis and differentiation degree. The high expressions of CK7 and TTF-1 in serum of patients are expected to be potential prognostic indicators for lung cancer complicated with SVCS.