Molecular biomarkers screened by next-generation RNA sequencing for non-sentinel lymph node status prediction in breast cancer patients with metastatic sentinel lymph nodes

Feng, Liang; Qu, Hongzhu; Lin, Qiang; Yang, Yadong; Ruan, Xiuhang; Zhang, Bo; Liu, Yi; Yu, Chunjing; Zhang, Hongyan; Fang, Xiangdong; Hao, Xiaopeng

doi:10.1186/s12957-015-0642-2

Cited by 24 publications

(21 citation statements)

References 39 publications

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“…Pursuant to the next-generation RNA sequencing study by Feng Liang et al [14] in non-SLN-positive group, CYP2A13, KLK11, and CLEC3A demonstrated higher overexpression. Biomarkers identified in this study can provide a new understanding of the mechanism of breast and lymph node involvement, as well as the selection of patients for surgery.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been indicated that KLK11 expression is regulated by steroid hormones such as estrogen [23] . CLEC3A and KLK11 are not normally expressed in lymph node tissue [14] . Furthermore, there are limited investigations on the presence of this biomarker in metastatic lymph nodes in breast cancer.…”

Section: Introductionmentioning

confidence: 95%

“…According to the recent next generation sequencing studies, CLEC3A and KLK11, are overexpressed in metastatic lymph nodes [14] . CLEC3A is a protein related to the great family of C-type lectins and can be seen in normal human breast tissue, but not in any other normal human tissue [15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

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Novel Biomarkers Aim at Detecting Metastatic Sentinel Lymph Nodes in Breast Cancer

Bakaeean

Gholamin

Yazdi

et al. 2020

ibj

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Background: Intra-operative molecular diagnostic assays are currently used for the detection of lymph node metastases. The objective of this study was to find new biomarkers to improve diagnostic accuracy in the detection of metastatic axillary lymph nodes in breast cancer patients. Methods: We applied an absolute quantitative real-time RT-PCR to quantitate the expression of CK19, KLK11, and CLEC3A mRNAs in 79 FFPE SLNs from 35 breast cancer patients. The CK19 was confirmed as a standard biomarker, and the level of expression of selected new markers, KLK11 and CLEC3A, was evaluated in pathologically negative and positive SLNs by using absolute quantitative real-time PCR. Results: The overall concordance of the CK19 gene with pathological results was 92.4% (less than 250 copies) in negative SLNs and 85% in positive SLNs (more than 250 copies). The sensitivity and specificity of CK19, which were detected by real-time PCR, was 85% and 46%, respectively. Our results revealed that lower CLEC3A was associated with more lymph node involvement. We could set a cutoff point for CLEC3A with the sensitivity of 78% and specificity of 60%. Also, the mean KLK11 had a statistically significant reverse correlation with tumor grade (p = 0.017). Higher CK19 levels were related to more tumor invasion (p < 0.0001). Conclusion: Regarding the findings, CLEC3A along with CK19 can be used as a promising marker with high sensitivity and specificity for the detection of metastatic SLN.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Novel Biomarkers Aim at Detecting Metastatic Sentinel Lymph Nodes in Breast Cancer

Bakaeean

Gholamin

Yazdi

et al. 2020

ibj

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“…Although there is a history of RNA detection in cancers [28,29] , there are methodological difficulties associated with this type of test, because generally it requires working with fresh biological materials, RNase-free reagents and under conditions which protect RNA integrity and prevent contamination with cellular RNase and between samples.…”

Section: Discussionmentioning

confidence: 99%

Detection of E6/E7 human papilloma virus (HPV) transcripts in lymph nodes of patients with cervical cancer

Basiletti¹,

Soderini²,

Picconi³

et al. 2017

Integr Cancer Sci Therap

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Volume 4(5): [1][2][3][4][5] types that taxonomically correspond to A7 (HPV 18, 39, 45, 59 and 68) and A9 species (HPV 16,31, 33, 35, 52 and 58) Hospital Nacional "Profesor Alejandro Posadas", Argentina 5Hospital Municipal "Juan A. Fernández", Argentina AbstractPersistent high risk Human Papillomavirus (HPV) infection is necessary for the development of cervical cancer (CC). HPV carcinogenesis is based on viral E6 and E7 proteins' capacity to interfere in cell proliferation control. The metastasis status of pelvic lymph nodes (PLN) is a critical parameter in post-operative decisions on adjuvant therapy, given its strong correlation with recurrence in CC. In order to complement the histopathological evaluation of subclinical node metastases, we evaluated the application of a commercial HPV E6 / E7 mRNA kit, to detect viral messenger RNAs in lymph nodes and tumors of patients with CC.Forty five cervical primary tumors and 152 PLN ( 3-4 from each patient) were included. HPVs were typed in tumors by PCR (polymerase chain reaction) using generic primers PGMY and reverse line blot hybridization (RLB) with type-specific oligo probes corresponding to 37 HPV types that infect the anogenital tract. PNL were collected in RNAlater (Invitrogen) and mRNA was extracted using the MiniMag (Biomerieux) system. Detection of E6 and E7 mRNAs corresponding to HPVs types 16, 18, 31, 33 and 45 was carried out using isothermal real time PCR (NucliSENS EasyQ HPV, Biomerieux).HPV was detected in the tumors of 42 patients; the viral types identified were HPV16 (n = 32), HPV18 (n = 5), HPV31 (n = 3), HPV45 (n = 2), HPV59 (n = 1) and HPV73 (n = 1). These last 2 cases were not considered in the study because the mRNA detection system does not include these viral types. Also excluded were 2 cases whose tumors were HPV negative. There was a high correlation between the histological and virological results. Seventy-two percent of the histologically positive PLN were positive for E6-E7 mRNA; while 93% (125/134) of the negative PLN were also negative for E6-E7 mRNA assay. There was, however 8% (9/134) of negative PLN in which viral messengers were detected.Patients' follow up was limited (4 years) and except for two patients who died (both positive for HPV 45) in the period under review, no recurrences were recorded in any of the patients included in the study.The presence of HPV in PLN may indicate a metastasis, as since the virus is not able of producing viremia or invading tissues it can only be "transported" by the cancer cell. The presence of HPV mRNA indicates viral genome transcription, a process which occurs in a lymph node only in CC metastatic cells, as these viruses can only replicate in epithelial-origin cells. Therefore, the findings of these mRNAs in the negative pelvic lymph nodes point out a very early metastasis, detectable at molecular level, but unobservable on histological diagnosis.The commercial kits for HPV E6/E7 mRNA detection, usually applied for the cervical disease management, may be used also to evaluate PLN biopsie...

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“…Gene expression profiling of the SLN was performed by Liang et al [21] in a small study to predict non-SLN status using next generation sequencing: They identified 103 specifically expressed genes in the non-SLN-negative group and 47 in the non-SLN-positive group. Only 2 protein-encoding genes were identified with high expression levels.…”

Section: Models For Prediction Of Nodal Metastasismentioning

confidence: 99%

Lymph Nodes in Breast Cancer - What Can We Learn from Translational Research

Peintinger¹,

Reitsamer²,

Smidt³

et al. 2018

Breast Care

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Clinical observations about lack of survival benefit after extensive axillary surgery and biological discordance between primary breast tumors and axillary lymph nodes raise the question of the actual metastatic potential of axillary nodal disease. The exploration of intratumoral heterogeneity and detection of genomic differences between the primary and lymph nodes indicate some similarity between the number of mutations in synchronous axillary node metastases and those in the primary lesion, suggesting a favorable prognosis. The hematogenous route of metastasis needs to be considered in findings of different subclones between nodal and distant metastases. Modern tools such as whole-genome sequencing applied in multiple tumor areas may guide more precisely the extent of axillary surgery.

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Molecular biomarkers screened by next-generation RNA sequencing for non-sentinel lymph node status prediction in breast cancer patients with metastatic sentinel lymph nodes

Cited by 24 publications

References 39 publications

Novel Biomarkers Aim at Detecting Metastatic Sentinel Lymph Nodes in Breast Cancer

Novel Biomarkers Aim at Detecting Metastatic Sentinel Lymph Nodes in Breast Cancer

Detection of E6/E7 human papilloma virus (HPV) transcripts in lymph nodes of patients with cervical cancer

Lymph Nodes in Breast Cancer - What Can We Learn from Translational Research

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