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Prognostic value of molecular intratumor heterogeneity in primary oral cancer and its lymph node metastases assessed by mass spectrometry imaging

ABSTRACT: Different aspects of intra-tumor heterogeneity (ITH), which are associated with development of cancer and its response to treatment, have postulated prognostic value. Here we searched for the potential association between phenotypic ITH analyzed by mass spectrometry imaging (MSI) and the prognosis of head and neck cancer. The study involved tissue specimens resected from 77 patients with locally advanced oral squamous cell carcinoma, including 37 patients where matched samples of primary tumor and synchronous lymph node metastases were analyzed. A 3-year follow-up was available for all patients that enabled their separation into two groups: with no evidence of disease (NED, n=41) and with progressive disease (PD, n=36). After the on-tissue trypsin digestion, peptide maps of all cancer regions were segmented using an unsupervised approach to reveal their intrinsic heterogeneity. We found that intra-tumor similarity of spectra was higher in the PD group and diversity of clusters identified during image segmentation was higher in the NED group, which indicated a higher level of ITH in patients with more favorable outcomes. Furthermore, signature of molecular components that correlated with long-term outcomes could be associated with proteins involved in the immune functions. Hence, we proposed that a higher level of ITH revealed by MSI in cancers with a better prognosis could reflect the presence of heterotypic components of tumor microenvironment such as infiltrating immune cells enhancing the response to the treatment. LC-MALDI-MS/MS data deposited in this repository originate from protein lysates obtained from FFPE sections consecutive to sections dedicated to MSI measurements. The hypothetical identity of the MSI components was established by assignment of a component location on the m/z scale for the measured masses of tryptic peptides identified by LC-MALDI-MS/MS allowing ±0.05% mass tolerance.

INSTRUMENT(S): ultraflex

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Monika Pietrowska

LAB HEAD: Piotr Widlak

PROVIDER: PXD034958 | Pride | 2022-10-13

REPOSITORIES: Pride

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Prognostic Value of Molecular Intratumor Heterogeneity in Primary Oral Cancer and Its Lymph Node Metastases Assessed by Mass Spectrometry Imaging.

Kurczyk Agata A Gawin Marta M Paul Piotr P Chmielik Ewa E Rutkowski Tomasz T Pietrowska Monika M Widłak Piotr P

Molecules (Basel, Switzerland) 20220825 17

Different aspects of intra-tumor heterogeneity (ITH), which are associated with the development of cancer and its response to treatment, have postulated prognostic value. Here we searched for potential association between phenotypic ITH analyzed by mass spectrometry imaging (MSI) and prognosis of head and neck cancer. The study involved tissue specimens resected from 77 patients with locally advanced oral squamous cell carcinoma, including 37 patients where matched samples of primary tumor and s ...[more]

PMID: 36080226

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Project description:Intra-individual tumoral heterogeneity (ITH) is a hallmark of solid tumors and impedes accurate genomic diagnosis and selection of proper therapy. The purpose of this study was to identify ITH of ovarian serous adenocarcinomas (OSAs) and to determine the utility of ascitic cancer cells as a resource for mutation profiling in spite of ITH. We performed whole-exome sequencing, copy number profiling, and DNA methylation profiling of four OSA genomes using multiregional biopsies from 13 intraovarian lesions, 12 extraovarian tumor lesions (omentum/peritoneum), and ascitic cells. We observed substantial levels of heterogeneity in mutations and copy number alterations (CNAs) of the OSAs. We categorized the mutations into 'common', 'shared' and 'private' according to the regional distribution. Six common, 8 shared, and 24 private mutations were observed in known cancer-related genes,. but common mutations had a higher mutant allele frequency and included TP53 mutations in all four OSAs. Region-specific chromosomal amplifications and deletions involving BRCA1, PIK3CA, and RB1 were also identified. Of note, the mutations detected in ascitic cancer cells represented 92.3-100% of overall somatic mutations in the given case. Phylogenetic analyses of ascitic genomes predicted a polyseeding origin of somatic mutations in ascitic cells. Our results demonstrate that despite ITH, somatic mutations, CNAs, and DNA methylations in both âcommonâ category and cancer-related genes were highly conserved in ascitic cells of OSAs, highlighting the clinical relevance of genome analysis of ascitic cells. Ascitic tumor cells may serve as a potential resource to discover somatic mutations of primary OSA with diagnostic and therapeutic relevance. The purpose of this study was to identify intra-individual tumor heterogenety of ovarian serous adenocarcinomas Four to nine different ovarian cancer areas from intraovarian and extra-ovarian lesions that were at least 1cm apart as well as 50 ml ascites were collected from the four OSA patients. Genomic DNA from tumor and matched normal samples were simultaneously hybridized onto the array. Total 29 array experiments were conducted.

			Action	DRS
	HNC-ITH-LN-mix-combined.mgf	Mgf
	HNC-ITH-LN-mix.dat	Other
	HNC-ITH-PT-mix-combined.mgf	Mgf
	HNC-ITH-PT-mix.dat	Other