Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis

Kim, Mijin; Kwon, Chae Hwa; Jang, Min Hee; Kim, Jeong Mi; Kim, Eun Heui; Jeon, Yun Kyung; Kim, Sang Soo; Choi, Kyung Un; Kim, In Joo; Park, Meeyoung; Kim, Bo Hyun

doi:10.3803/enm.2021.1132

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…Hendrix et al demonstrated that the gene RAB27B was associated with metastasis of breast cancer ( Hendrix et al, 2010 ). Other studies have identified mutated genes associated with early recurrence, including FAT3 and USH2A ( Kim et al, 2021 ; Qiu et al, 2021 ). In addition, other researchers have also used multi-omics data to identify biomarkers for cancer recurrence and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer

Wang

Wen

et al. 2023

Front. Genet.

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Cancer remains a formidable challenge in medicine due to its propensity for recurrence and metastasis, which can result in unfavorable treatment outcomes. This challenge is particularly acute for early-stage patients, who may experience recurrence and metastasis without timely detection. Here, we first analyzed the differences in clinical characteristics among the primary tumor, recurrent tumor, and metastatic tumor in different stages of cancer, which may be caused by the molecular level. Moreover, the importance of predicting early cancer recurrence and metastasis is emphasized by survival analyses. Next, we used a multi-omics approach to identify key molecular changes associated with early cancer recurrence and metastasis and discovered that early metastasis in cancer demonstrated a high degree of genomic and cellular heterogeneity. We performed statistical comparisons for each level of omics data including gene expression, mutation, copy number variation, immune cell infiltration, and cell status. Then, various analytical techniques, such as proportional hazard model and Fisher’s exact test, were used to identify specific genes or immune characteristics associated with early cancer recurrence and metastasis. For example, we observed that the overexpression of BPIFB1 and high initial B-cell infiltration levels are linked to early cancer recurrence, while the overexpression or amplification of ANKRD22 and LIPM, mutation of IGHA1 and MUC16, high fibroblast infiltration level, M1 polarization of macrophages, cellular status of DNA repair are all linked to early cancer metastasis. These findings have led us to construct classifiers, and the average area under the curve (AUC) of these classifiers was greater than 0.75 in The Cancer Genome Atlas (TCGA) cancer patients, confirming that the features we identified could be biomarkers for predicting recurrence and metastasis of early cancer. Finally, we identified specific early sensitive targets for targeted therapy and immune checkpoint inhibitor therapy. Once the biomarkers we identified changed, treatment-sensitive targets can be treated accordingly. Our study has comprehensively characterized the multi-omics characteristics and identified a panel of biomarkers of early cancer recurrence and metastasis. Overall, it provides a valuable resource for cancer recurrence and metastasis research and improves our understanding of the underlying mechanisms driving early cancer recurrence and metastasis.

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Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer

Wang

Wen

et al. 2023

Front. Genet.

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“…Yet, there is little information about their somatic mutations in cancer. Somatic mutations in SLC16A1 [ 18 ], SLC16A7 [ 24 , 64 ], SLC9A2 [ 91 ], SLC9A3 [ 42 ], SLC9A8 [ 48 ], SLC9A9 [ 31 , 85 ], SLC4A2 [ 22 , 88 ], SLC4A4 [ 53 ], SLC4A7 [ 34 ], and SLC4A8 [ 47 ] have been reported in human cancers (Table 1 ). However, their abundance across large pan-cancer cohorts has not been analysed.…”

Section: Pan-cancer Analysis Of Somatic Mutations In Abt-slcsmentioning

confidence: 99%

What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?

White,

Swietach

2023

Pflugers Arch - Eur J Physiol

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Acidosis is a chemical signature of the tumour microenvironment that challenges intracellular pH homeostasis. The orchestrated activity of acid-base transporters of the solute-linked carrier (SLC) family is critical for removing the end-products of fermentative metabolism (lactate/H+) and maintaining a favourably alkaline cytoplasm. Given the critical role of pH homeostasis in enabling cellular activities, mutations in relevant SLC genes may impact the oncogenic process, emerging as negatively or positively selected, or as driver or passenger mutations. To address this, we performed a pan-cancer analysis of The Cancer Genome Atlas simple nucleotide variation data for acid/base-transporting SLCs (ABT-SLCs). Somatic mutation patterns of monocarboxylate transporters (MCTs) were consistent with their proposed essentiality in facilitating lactate/H+ efflux. Among all cancers, tumours of uterine corpus endometrial cancer carried more ABT-SLC somatic mutations than expected from median tumour mutation burden. Among these, somatic mutations in SLC4A3 had features consistent with meaningful consequences on cellular fitness. Definitive evidence for ABT-SLCs as ‘cancer essential’ or ‘driver genes’ will have to consider microenvironmental context in genomic sequencing because bulk approaches are insensitive to pH heterogeneity within tumours. Moreover, genomic analyses must be validated with phenotypic outcomes (i.e. SLC-carried flux) to appreciate the opportunities for targeting acid-base transport in cancers.

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“…WES has been applied to study PTMC in several cohorts and revealed potential biomarkers and therapeutic targets. 3,4 However, these studies used surgically resected tissue samples, which are typical materials for genetic molecular Liyuan Ma and Luying Gao contributed equally to this work.…”

Section: Introductionmentioning

confidence: 99%

“…Whole‐exome sequencing (WES) is a powerful next‐generation sequencing (NGS) technique that can provide comprehensive information on the genomic landscape of tumors. WES has been applied to study PTMC in several cohorts and revealed potential biomarkers and therapeutic targets 3,4 . However, these studies used surgically resected tissue samples, which are typical materials for genetic molecular testing.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of whole‐exome sequencing in fine‐needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations

Ma,

Gao,

et al. 2024

Clinical Genetics

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Genetic profiling is important for assisting the management of papillary thyroid microcarcinoma (PTMC). Although whole‐exome sequencing (WES) of surgically resected PTMC tissue has been performed and revealed potential prognostic biomarkers, its application in PTMC fine‐needle aspiration (FNA) specimens has not been explored. This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single‐nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC FNA samples, the most frequently mutated genes were BRAF and ANKRD18B, and the four driver genes were BRAF, AFF3, SRCAP, and EGFR. We also identified several germline cancer predisposing gene mutations. The results suggest that WES of FNA specimens is feasible for PTMC and can identify novel genetic mutations.

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Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis

Cited by 4 publications

References 35 publications

Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer

Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer

What can we learn about acid-base transporters in cancer from studying somatic mutations in their genes?

Feasibility of whole‐exome sequencing in fine‐needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations

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