Summary of Study ST003599
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002227. The data can be accessed directly via it's Project DOI: 10.21228/M8RR8B This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003599 |
| Study Title | Multi-omic profiling of squamous cell lung cancer identifies metabolites and related genes associated with squamous cell carcinoma |
| Study Summary | Squamous cell lung carcinoma (SqCC) is the second most common histological subtype of lung cancer. Besides tumor-initiating and promoting DNA, RNA, and epigenetic alterations, aberrant cell metabolism is a hallmark of carcinogenesis. This study aimed to identify SqCC-specific metabolites and key gene regulators that could eventually be used as new anticancer targets. Transcriptional, proteomic, and metabolomic data were gathered for a cohort of resected lung cancers. SqCC-specific differentially expressed genes were integrated with proteogenomic and metabolic data using genome scale metabolic models (GEMs). Findings were validated in cohorts of tumors, normal specimens, and cell lines. In-situ protein expression of SLC6A8 was investigated. Differential gene expression analysis identified a list of 280 strictly SqCC-specific genes. Metabolic profiling identified 7 SqCC-specific metabolites, of which increased creatine and decreased phosphocholine levels matched to SqCC-specific expression of SLC6A8 and CHKA, by matching genes to metabolites through genome scale metabolic models (GEMs) and the Reactome pathways database. Expression of both genes appeared tumor cell-associated, and in particular, the elevated expression of SLC6A8 identified SqCC also in stage IV disease. Elevated creatine levels and overexpression of its transporter SLC6A8 appear a distinct metabolic feature of SqCC. Considering ongoing clinical trials in other malignancies, exploring SLC6A8-inhibition in SqCC appears motivated based on a metabolic addiction hypothesis. |
| Institute | Lund University |
| Department | oncology |
| Laboratory | Maria Planck and Johan Staaf |
| Last Name | Arbajian |
| First Name | Elsa |
| Address | Medicin Village 404, 22381 Lund, SWEDEN |
| elsa.arbajian@med.lu.se | |
| Phone | 0046700253200 |
| Submit Date | 2024-11-26 |
| Total Subjects | 73 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-07-25 |
| Release Version | 1 |
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Project:
| Project ID: | PR002227 |
| Project DOI: | doi: 10.21228/M8RR8B |
| Project Title: | Multi-omic profiling of squamous cell lung cancer identifies metabolites and related genes associated with squamous cell carcinoma |
| Project Summary: | Squamous cell lung carcinoma (SqCC) is the second most common histological subtype of lung cancer. Besides tumor-initiating and promoting DNA, RNA, and epigenetic alterations, aberrant cell metabolism is a hallmark of carcinogenesis. This study aimed to identify SqCC-specific metabolites and key gene regulators that could eventually be used as new anticancer targets. Transcriptional, proteomic, and metabolomic data were gathered for a cohort of resected lung cancers. SqCC-specific differentially expressed genes were integrated with proteogenomic and metabolic data using genome scale metabolic models (GEMs). Findings were validated in cohorts of tumors, normal specimens, and cell lines. In-situ protein expression of SLC6A8 was investigated. Differential gene expression analysis identified a list of 280 strictly SqCC-specific genes. Metabolic profiling identified 7 SqCC-specific metabolites, of which increased creatine and decreased phosphocholine levels matched to SqCC-specific expression of SLC6A8 and CHKA, by matching genes to metabolites through genome scale metabolic models (GEMs) and the Reactome pathways database. Expression of both genes appeared tumor cell-associated, and in particular, the elevated expression of SLC6A8 identified SqCC also in stage IV disease. Elevated creatine levels and overexpression of its transporter SLC6A8 appear a distinct metabolic feature of SqCC. Considering ongoing clinical trials in other malignancies, exploring SLC6A8-inhibition in SqCC appears motivated based on a metabolic addiction hypothesis. |
| Institute: | Lund University |
| Department: | Oncology |
| Laboratory: | Maria Planck and Johan Staaf |
| Last Name: | Arbajian |
| First Name: | Elsa |
| Address: | Medicon Village 404, 22381 Lund, SWEDEN |
| Email: | elsa.arbajian@med.lu.se |
| Phone: | 0046700253200 |
Subject:
| Subject ID: | SU003728 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Species Group: | Mammals |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Group_Histology |
|---|---|---|
| SA392407 | JS-51 | AC |
| SA392408 | JS-32 | AC |
| SA392409 | JS-33 | AC |
| SA392410 | JS-35 | AC |
| SA392411 | JS-36 | AC |
| SA392412 | JS-40 | AC |
| SA392413 | JS-41 | AC |
| SA392414 | JS-43 | AC |
| SA392415 | JS-44 | AC |
| SA392416 | JS-48 | AC |
| SA392417 | JS-49 | AC |
| SA392418 | JS-55 | AC |
| SA392419 | JS-27 | AC |
| SA392420 | JS-56 | AC |
| SA392421 | JS-57 | AC |
| SA392422 | JS-59 | AC |
| SA392423 | JS-63 | AC |
| SA392424 | JS-64 | AC |
| SA392425 | JS-66 | AC |
| SA392426 | JS-68 | AC |
| SA392427 | JS-71 | AC |
| SA392428 | JS-72 | AC |
| SA392429 | JS-73 | AC |
| SA392430 | JS-31 | AC |
| SA392431 | JS-01 | AC |
| SA392432 | JS-26 | AC |
| SA392433 | JS-17 | AC |
| SA392434 | JS-05 | AC |
| SA392435 | JS-06 | AC |
| SA392436 | JS-08 | AC |
| SA392437 | JS-09 | AC |
| SA392438 | JS-13 | AC |
| SA392439 | JS-15 | AC |
| SA392440 | JS-14 | AC |
| SA392441 | JS-21 | AC |
| SA392442 | JS-22 | AC |
| SA392443 | JS-23 | AC |
| SA392444 | JS-58 | LCC |
| SA392445 | JS-42 | LCC |
| SA392446 | JS-70 | LCC |
| SA392447 | JS-07 | LCC |
| SA392448 | JS-16 | LCC |
| SA392449 | JS-34 | LCC |
| SA392450 | JS-50 | LCC |
| SA392451 | JS-65 | LCC |
| SA392452 | JS-25 | LCC |
| SA392453 | JS-24 | LCC |
| SA392454 | JS-39 | LCNEC |
| SA392455 | JS-03 | LCNEC |
| SA392456 | JS-29 | LCNEC |
| SA392457 | JS-69 | LCNEC |
| SA392458 | JS-67 | LCNEC |
| SA392459 | JS-61 | LCNEC |
| SA392460 | JS-11 | LCNEC |
| SA392461 | JS-46 | LCNEC |
| SA392462 | JS-19 | LCNEC |
| SA392463 | JS-53 | LCNEC |
| SA392464 | JS-12 | SqCC |
| SA392465 | JS-04 | SqCC |
| SA392466 | JS-18 | SqCC |
| SA392467 | JS-02 | SqCC |
| SA392468 | JS-45 | SqCC |
| SA392469 | JS-30 | SqCC |
| SA392470 | JS-28 | SqCC |
| SA392471 | JS-47 | SqCC |
| SA392472 | JS-20 | SqCC |
| SA392473 | JS-52 | SqCC |
| SA392474 | JS-62 | SqCC |
| SA392475 | JS-54 | SqCC |
| SA392476 | JS-60 | SqCC |
| SA392477 | JS-10 | SqCC |
| SA392478 | JS-37 | SqCC |
| SA392479 | JS-38 | SqCC |
| Showing results 1 to 73 of 73 |
Collection:
| Collection ID: | CO003721 |
| Collection Summary: | Tumor pieces were collected from patients with early-stage lung cancer undergoing tumor removal surgery at the Skåne University Hospital in Lund. The samples were fresh frozen and kept at -80℃. |
| Sample Type: | Lung |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR003737 |
| Treatment Summary: | The patients included in this study underwent surgical removal of their lung tumors, they had not been subjected to neoadjuvant cancer treatment. |
Sample Preparation:
| Sampleprep ID: | SP003735 |
| Sampleprep Summary: | Metabolite extraction solution (50% methanol, 30% acetonitrile, 20% ultrapure water, 5 µM final concentration valine-d8) was added to each sample tube and incubated at -20°C for one hour. The samples were placed on a Thermomixer for 15 min at 4°C and maximum speed . After final centrifugation at max speed for 10 min at 4°C, the supernatants were transferred into LC-MS vials and kept at -80°C prior to mass spectrometry analysis |
Chromatography:
| Chromatography ID: | CH004491 |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | SeQuant ZIC-HILIC (150 x 2.1mm,5um) |
| Column Temperature: | 40°C |
| Flow Gradient: | 0-2 min: 80% B; 2-17 min: linear gradient from 80% B to 20% B; 17-17.1 min: linear gradient from 20% B to 80% B; 17.1-22.5min: hold at 80% B |
| Flow Rate: | 0.200 mL/min |
| Solvent A: | 100% Water; 20 mM ammonium carbonate; 0.05% ammonium hydroxide |
| Solvent B: | 100% Acetonitrile |
| Chromatography Type: | HILIC |
Analysis:
| Analysis ID: | AN005914 |
| Analysis Type: | MS |
| Chromatography ID: | CH004491 |
| Num Factors: | 4 |
| Num Metabolites: | 139 |
| Units: | peak area |