Midkine is a serum and urinary biomarker for the detection and prognosis of non-small cell lung cancer

Xia, Xin; Lu, Jianjun; Zhang, Shui-Shen; Su, Chunhua; Hy, Luo

doi:10.18632/oncotarget.13865

Cited by 25 publications

(18 citation statements)

References 17 publications

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“…Unfortunately, the reason behind the s‐MK positive rate being relatively low, and lower than the CEA positive rate in stage III, was unclear. Although high s‐MK (>400 pg/mL) was reported to be a poor prognostic factor in patients with non‐small cell lung cancer, we could not confirm such a prognostic impact of s‐MK in gastric cancer.…”

Section: Discussioncontrasting

confidence: 69%

“…Yamashita et al showed that s‐MK levels were positively associated with immunohistochemical staining scores in patients with head and neck squamous cell carcinoma. Moreover, Xia et al showed that the immunoreactivity of MK was significantly associated with s‐MK in patients with lung cancer. Actually, their study included 91 patients with adenocarcinoma among the 153 with lung cancer.…”

Section: Discussionmentioning

confidence: 99%

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Diagnostic impact of high serum midkine level in patients with gastric cancer

Ito

Oshima

Yajima

et al. 2019

Annals of Gastroent Surgery

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Aim We evaluated the diagnostic impact of serum midkine (s‐MK) levels in patients with gastric cancer using a monoclonal antibody enzyme‐linked immunosorbent assay system (ELISA) to detect s‐MK levels. Methods Serum samples were obtained from 131 patients with gastric cancer including stage I (n = 71), stage II (n = 28), stage III (n = 16), and stage IV (n = 16) before surgery. Serum samples were analyzed using ELISA to detect soluble midkine. A cut‐off value was fixed at 421 pg/mL, and the sample divided into two groups: a high s‐MK group and a low s‐MK group. Clinicopathological factors and prognosis were compared between these two groups using univariate and multivariate analyses. Comparison of two groups was analyzed by Fisher's exact probability test. Statistical significance was considered at P < 0.05. Results High s‐MK was significantly associated with high carcinoembryonic antigen (CEA) (P < 0.01). Positive rate of s‐MK was higher than the positive rates of CEA in patients with stage I/II gastric cancer. Combination with CEA + CA19‐9 + s‐MK increased the positive rates of patients with stage I/II gastric cancer. No other clinicopathological factors were associated with s‐MK. Although the high s‐MK group showed worse overall survival than the low s‐MK group, the difference was not statistically significant. Conclusion s‐MK level is increased even during early‐stage gastric cancer. Combined with s‐MK, the positive rate of CEA + CA19‐9 was increased in patients with stage I/II gastric cancer.

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Section: Discussioncontrasting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Diagnostic impact of high serum midkine level in patients with gastric cancer

Ito

Oshima

Yajima

et al. 2019

Annals of Gastroent Surgery

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“…Recently, relatively rapid improvement has been made in the treatment of LUAD, but the prognosis and treatment efficacy of LUAD remains insufficient. The overall 5-year survival rate for all types of lung cancer, including LUAD, remains very low (<15%) ( 10 – 14 ). Therefore, it is essential to expand and improve understanding of the principal molecular mechanisms associated with LUAD.…”

Section: Introductionmentioning

confidence: 99%

The expression of HOXA13 in lung adenocarcinoma and its clinical significance: A study based on The Cancer Genome Atlas, Oncomine and reverse transcription‑quantitative polymerase chain reaction

Deng

Zhang

et al. 2018

Oncol Lett

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Previous studies have investigated the association between HOXA13 and non-small cell lung cancer. However, the role of HOXA13 expression in the occurrence and progression of lung adenocarcinoma (LUAD) has not yet been investigated. In the present study, HOXA13-related data mining of The Cancer Genome Atlas (TCGA), polymerase chain reaction (PCR) data from our cases and the case information in Oncomine was conducted for validation. The expression data of HOXA13 in lung cancer cell lines were also collected from the Cancer Cell Line Encyclopedia (CCLE) database for further verification. A comprehensive meta-analysis of the expression of HOXA13 was also performed, integrating the data of TCGA, in-house PCR and Oncomine. Genes that were co-expressed with HOXA13 were subsequently identified through cBioPortal and Multi Experiment Matrix (MEM), and the potential role and mechanism of HOXA13 in LUAD was investigated. The expression value of HOXA13 in the LUAD group, which comprised 237 cases, was 3.74±2.694, significantly higher than its expression value in the non-cancerous group (0.92±0.608, P<0.001). The pooled SMD for HOXA13 was 0.346 (95% CI, 0.052–0.640; P=0.068; I2=51.3%; P=0.021), The meta-analysis of diagnostic tests revealed that the area under the summary receiver operating characteristic curve (SROC) was 0.78 (95% CI, 0.75–0.82). The results demonstrated that HOXA13 is highly expressed in LUAD. In addition to the studies on HOXA13 expression in tissues, the expression data of HOXA13 in lung cancer cell lines were also collected from the CCLE database for further verification of these conclusions. Genes that were co-expressed with HOXA13 were identified for pathway analysis. The most enriched Gene Ontology terms in the genes co-expressed with HOXA13 were positive regulation of transcription from RNA polymerase II promoter, signal transduction and positive regulation of GTPase activity in biological process; cytoplasm, integral component of membrane and plasma membrane in cellular component; and significantly involved in protein binding, transcription factor activity, sequence-specific DNA binding and sequence-specific DNA binding in molecular function. Kyoto Encyclopedia of Genes and Genomes analysis revealed that these target genes were clearly involved in Pathways in cancer, Proteoglycans in cancer and cAMP signaling pathway. The hub genes obtained from the four protein-protein interaction networks were associated with HOXA13. The results of the bioinformatics research in the present study revealed that HOXA13 may influence the expression of these hub genes in such a way as to promote the occurrence and development of LUAD. In conclusion, the expression of HOXA13 in patients with LUAD and its potential clinical value were analyzed comprehensively in the present study using data from a variety of sources. Through bioinformatics analysis, evidence that HOXA13 may promote the occurrence and development of LUAD was obtained.

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“…For instance, Xu et al characterized the high level of serous Cripto‐1 in NSCLC patients, which was associated with poorer prognosis and possessed the potential as a novel biomarker for diagnostic purpose . Xia et al proposed that Midkine was a serum and urinary biomarker for the screening and prognostic scoring of NSCLC . Kerenidi et al demonstrated that the multifunctional cytokine, Osteopontin, was positively correlated with both VEGF and MMP‐9 and might serve as a prognostic biomarker in lung cancer .…”

Section: Discussionmentioning

confidence: 99%

Serous IFNA3 predicts unfavorable prognosis in lung cancer via abnormal activation of AKT signaling

Cong

2019

IUBMB Life

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This study addresses the demand through datamining The Cancer Genome Atlas (TCGA) database and elucidates mechanistic involvements of interferon alpha 8 (IFNA8) in lung cancer. The overall survival and disease-free survival of lung cancer patients in respect to IFNA8 expression level were analyzed. IFNA8 expression levels in both serum and tumor tissue were determined by real-time polymerase chain reaction. The diagnostic value of serous IFNA8 in lung cancer was assessed by receiver operating characteristic (ROC) curve analysis. Cell viability and proliferation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Cell Counting Kit-8 assays. in vivo pro-tumor effect of IFNA8 was evaluated using xenograft tumor model. The metastasis-prone behaviors were determined by Transwell chamber assay and tail vein-injection in mice. Protein levels of p-AKT, total AKT, and endogenous reference actin were analyzed by western blot. We uncovered high IFNA8 associated with unfavorable overall survival and disease-free survival in lung cancer patients from TCGA. We further characterized the aberrant over-expression of IFNA8 in both peripheral blood and solid tumor from our clinical patient panel, and ROC analysis suggested its potential diagnostic value. Ectopic over-expression of IFNA8 promoted viability and proliferation in both A549 and H1299 cells in vitro and accelerated xenograft tumor growth in vivo. Furthermore, IFNA8 facilitated migration, invasion, and metastasis of A549 cells in vivo. Mechanistically, we disclosed the over-activation of AKT signaling in IFNA8-proficient A549 cells, inhibition of which completely abolished the pro-tumor effects of IFNA8. We have identified IFNA8 as a novel biomarker for either diagnostic or prognostic purpose in lung cancer, which is mechanistically associated with abnormal activation of AKT signaling. K E Y W O R D SAKT signaling, biomarker, IFNA8, lung cancer

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Midkine is a serum and urinary biomarker for the detection and prognosis of non-small cell lung cancer

Cited by 25 publications

References 17 publications

Diagnostic impact of high serum midkine level in patients with gastric cancer

Diagnostic impact of high serum midkine level in patients with gastric cancer

The expression of HOXA13 in lung adenocarcinoma and its clinical significance: A study based on The Cancer Genome Atlas, Oncomine and reverse transcription‑quantitative polymerase chain reaction

Serous IFNA3 predicts unfavorable prognosis in lung cancer via abnormal activation of AKT signaling

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