Evidence map›Paper›PMID 34718915›Full record

ArticleAnnals of surgical oncology2022

Establishing Novel Molecular Subtypes of Appendiceal Cancer.

Mary Garland-Kledzik, Anthony Scholer, Miquel Ensenyat-Mendez, Javier I J Orozco, Adam Khader, Juan Santamaria-Barria, Trevan Fischer, Alessio Pigazzi, Diego M Marzese

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Article in Annals of surgical oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Mary Garland-KledzikDivision of Surgical Oncology, West Virginia University, Morgantown, WV, USA. mgkledzikmd@gmail.com.
Anthony ScholerDepartment of Surgery, Saint John's Cancer Institute at Providence St. John's Health Center, Santa Monica, CA, USA.
Miquel Ensenyat-MendezCancer Epigenetic Laboratory, Health Research Institute of the Balearic Islands (IdISBa), Palma, Islas Baleares, Spain.
Javier I J OrozcoCancer Epigenetics Laboratory, Saint John's Cancer Institute at Providence St. John's Health Center, Santa Monica, CA, USA.
Adam KhaderDepartment of Surgery, Saint John's Cancer Institute at Providence St. John's Health Center, Santa Monica, CA, USA.
Juan Santamaria-BarriaDepartment of Surgery, Saint John's Cancer Institute at Providence St. John's Health Center, Santa Monica, CA, USA.
Trevan FischerDepartment of Surgery, Saint John's Cancer Institute at Providence St. John's Health Center, Santa Monica, CA, USA.
Alessio PigazziColon and Rectal Surgery, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY, USA.
Diego M MarzeseCancer Epigenetic Laboratory, Health Research Institute of the Balearic Islands (IdISBa), Palma, Islas Baleares, Spain.

Funding

AES19 Project PI19/01514Miguel Servet Project CP17/00188
6 · The paper itself

Abstract

purposeAppendiceal cancer is a rare disease process with complex treatment strategies. The objective of this study was to identify mutation-based genetic subtypes that may differ from the current histological classification, compare the genetic make-up of primaries and metastases, and find novel targetable alterations.

methodsThe analyses involved the curation and normalization of gene mutation panels from appendiceal adenocarcinoma and mucinous adenocarcinoma (n = 196) stored in the AACR GENIE Database v6.0. Genes mutated in less than one patient and tumors profiled with incomplete mutation panels were excluded from the study. The optimal number of AC subtypes was established using the Nonnegative Matrix Factorization algorithm. Statistical comparisons of mutation frequencies were performed using Pearson's χ

resultsAC patients were stratified into five mutation subtypes, based on a final set of 41 cancer-related genes. AC0 had no mutations. The most frequently mutated genes varied between the subtypes were: AC1: KRAS (91.9%) and GNAS (77.4%); AC2: KRAS (52.5%), APC (32.5%), and GNAS (30%); AC3: KMT2D (38.7%), TP53 (38.7%), KRAS (35.5%), EP300 (22.6%); and AC4: TP53 (97.2%), KRAS (77.8%), and SMAD4 (36.1%). Additionally, AC3 was less likely to be mucinous (22.6% vs. 50.0-74.2%, p < 0.001) and had a higher mutation frequency (3.6 vs. 0-3.1, p < 0.001). There were no significant differences between primary tumors and metastases in the 41 assessed genes (p = 0.35).

conclusionsThe characterization of these subtypes suggests a need for molecular approaches to complement anatomical and histopathological staging for AC. A prospective comparison of subtype prognosis and response to surgery and adjuvant treatment is needed to identify the clinical applications of the novel molecular subtypes.

Indexed as

Adenocarcinoma, MucinousAppendiceal NeoplasmsBiomarkers, TumorHumansMutationOncogenesProspective StudiesBiomarkers, Tumor

Identifiers

PMID34718915

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.