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Increased expression of TMED2 is an unfavorable prognostic factor in patients with breast cancer.

ABSTRACT: Background: We obtained 2 types of clones which were termed SC (sphere-shaped clone) and NSC (non-sphere-shaped clone) from 4T1 cells by monoclonal culture. SC and NSC were distinct in morphology, surface marker, metabolism and proliferation rate. With the transcriptome sequencing data analysis, we found TMED2 expressed higher in SCs. TMED2 was a member of the transmembrane emp24 domain and might play roles in cancer cell proliferation. However, its prognostic roles in breast cancer remained unknown. We aimed to investigate the prognostic values of TMED2 in patients with breast cancer. Methods: We used UALCAN (http://ualcan.path.uab.edu) and the Human Protein Atlas (www.proteinatlas.org) to explore the TMED2 expression level and DNA methylation data between breast cancer and normal breast tissue. With Oncomine (www.oncomine.org), we investigated the copy number of TMED2 in breast cancer sample and normal breast tissue. We used the Kaplan-Meier Plotter database (http://kmplot.com/analysis) to analyze prognostic values of TMED2 mRNA expression in all breast cancers and in different intrinsic subtypes. Moreover, protein expression levels of TMED2 were confirmed by Western blot in breast cancer tissues and normal mammary tissue as well as SCs and NSCs. Results: TMED2 significantly upregulated in breast cancer patients compared to normal mammary samples. Meanwhile, the increased expression of TMED2 mRNA was closely associated with reduced overall survival (OS) in all breast cancers, and with reduced OS in patients with ER-positive, Luminal A or Luminal B breast cancer subtypes. Moreover, western blot confirmed that TMED2 increased expressed was correlated with the reduced OS at protein levels. Conclusion: Increased expression of TMED2 was significantly related to unfavorable outcomes in patients with breast cancer. Thus, we supposed TMED2 is oncogenic and a potential target for breast cancer therapy and these preliminary findings require further study to determine whether TMED2-targeting reagents might be developed for clinical application in breast cancer.

SUBMITTER: Lin X

PROVIDER: S-EPMC6497492 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Increased expression of TMED2 is an unfavorable prognostic factor in patients with breast cancer.

Lin Xia X Liu Jian J Hu Shu Fang SF Hu Xun X

Cancer management and research 20190318

<b>Background:</b> We obtained 2 types of clones which were termed SC (sphere-shaped clone) and NSC (non-sphere-shaped clone) from 4T1 cells by monoclonal culture. SC and NSC were distinct in morphology, surface marker, metabolism and proliferation rate. With the transcriptome sequencing data analysis, we found <i>TMED2</i> expressed higher in SCs. TMED2 was a member of the transmembrane emp24 domain and might play roles in cancer cell proliferation. However, its prognostic roles in breast cance ...[more]

PMID: 31114314

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Project description:The clinical utility and prognostic impact of presumed primary breast or ovarian cancer among patients with an unfavorable subset of cancer of unknown primary site (CUP) remains unclear. We aimed to evaluate the clinical relevance of the presumed primary site of CUP and the clinical outcome of site-specific therapy based on such presumptions.Patients referred to our center who were diagnosed with unfavorable-subset CUP and treated between April 2007 and March 2015 were enrolled in this study. Data were collected retrospectively from the hospital database and electronic medical records. Presumptive primary breast or ovarian cancer was based on histological and immunohistochemical analyses and metastatic patterns. The outcomes of patients with unfavorable-subset CUP with a putative primary site in the breast or ovary (P-CUP) and of patients with unfavorable-subset CUP, but without P-CUP (U-CUP), were assessed.A total of 780 patients were referred to our hospital with malignancy of unknown origin. Of these, 409 patients were diagnosed with CUP and 344 patients with unfavorable-subset CUP. Following clinicopathological examination, 40 (11.6%) of the 344 patients had P-CUP and the remaining 303 (88.3%) patients had U-CUP. In total, 136 patients received chemotherapy (22 with P-CUP and 114 with U-CUP). Among the 22 patients with P-CUP, three received hormonal therapy for breast cancer, and 19 received chemotherapy based on the presumed primary organ (breast, 4; ovaries, 15). Conventional platinum-based chemotherapy was administered to 105 patients with U-CUP and non-platinum drug treatment to nine patients. The objective response rates were 61.1% (95% confidence interval [CI]: 38.6-83.6) and 41.1% (95% CI: 31.8-50.4) for patients with P-CUP and U-CUP, respectively. The median overall survival durations were 50.0 months and 16.9 months (log-rank: P?=?0.002) for patients with P-CUP and U-CUP, respectively. P-CUP was identified as an independent predictor of good prognosis according to multivariate analysis.Patients with P-CUP had higher response rates and a better prognosis compared with patients with U-CUP. It might thus be reasonable to classify this subset as a new category of CUP with a favorable prognosis.

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Increased expression of TMED2 is an unfavorable prognostic factor in patients with breast cancer.

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Increased expression of TMED2 is an unfavorable prognostic factor in patients with breast cancer.

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