Pan-cancer analysis of oncogenic role of Programmed Cell Death 2 Like (PDCD2L) and validation in colorectal cancer

Our plain-English summary of Pan-cancer analysis of oncogenic role of Programmed Cell Death 2 Like (PDCD2L) and validation in colorectal cancer, by H. Gao, C. Xu, J. Liang, et al (Cancer Cell International, 2022).

The study

• Authors: H. Gao, C. Xu, J. Liang, S. Ge, F. Zhang, Y. Tuo, H. Shi, A. Han
• Journal: Cancer Cell International
• Published: 2022;22(1):100
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Programmed Cell Death 2 Like (PDCD2L) correlates with cell proliferation, apoptosis and mouse embryonic development. However, the role of PDCD2L in human cancers is unclear.

Methods: Multiple bioinformatic methods, in vitro function experiments and validation were performed to clarify the oncogenic role of PDCD2L in human cancers.

Results: Our study found that PDCD2L was aberrantly expressed in multiple types of human cancers, and associated with clinical stage and molecular subtype. Furthermore, overexpression of PDCD2L predicted poor overall survival in adrenocortical carcinoma(ACC), kidney chromophobe(KICH), acute myeloid leukemia(LAML), brain lower grade glioma(LGG),liver hepatocellular carcinoma(LIHC), mesothelioma(MESO), uveal melanoma(UVM) and poor diseases free survival in ACC, bladder urothelial carcinoma(BLCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), kidney renal clear cell carcinoma(KIRC), kidney renal papillary cell carcinoma(KIRP), LGG, LIHC, and UVM. PDCD2L expression was negatively associated with cancer associated fibroblast in breast invasive carcinoma (BRCA), lung squamous cell carcinoma (LUSC), sarcoma (SARC), stomach adenocarcinoma (STAD) and testicular germ cell tumors (TGCT). Mechanically, we found that PDCD2L expression was associated with apoptosis, invasion and cell cycle by investigating single cell sequencing data. For further validation, PDCD2Lwas highly expressed in colorectal cancer (CRC) cell lines and tissue samples compared with the normal colon cell line and non-tumor adjacent colorectal mucosa tissues. PDCD2L knockdown induced the apoptosis and proliferation of CRC cells.

Conclusions: Our study shows that the oncogenic role of PDCD2L in various cancers and PDCD2L could be served as a biomarker of CRC.

© 2022. The Author(s).

In plain English

This laboratory and database study looked at a gene called PDCD2L across many cancer types. It did not study asbestos. The authors analysed public cancer databases, tested tumor samples from 157 colorectal cancer patients at a hospital in Guangzhou, China, from 2013, and ran experiments in colorectal cancer cell lines. In the databases, PDCD2L was expressed at higher levels in many cancers than in corresponding non-tumor tissue. Patients whose tumors had higher-than-median PDCD2L had poorer overall survival in seven cancer types, including mesothelioma (P = 0.0077). For mesothelioma, no link was found with disease-free survival. The article does not say whether these mesotheliomas were pleural or peritoneal, and it gives no information on asbestos or other exposures. In the hospital samples, PDCD2L was higher in colorectal tumors than in nearby non-tumor bowel lining, but it was not associated with patients' survival. Lowering PDCD2L in two cell lines increased both programmed cell death (apoptosis) and cell growth. The authors concluded that PDCD2L could serve as a biomarker of colorectal cancer. They said its link with survival needs study in more patients.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Bioinformatic analysis of public cancer databases (pan-cancer), plus laboratory experiments in cell lines and validation in colorectal cancer tissue samples
• Who was studied: Public database data (ONCOMINE, TIMER2.0, GEPIA2, TISIDB, CancerSEA) across many cancer types, including mesothelioma. Also 157 paraffin-embedded colorectal cancer specimens and 140 non-tumor adjacent colorectal mucosa tissues (126 paired), collected January to December 2013 at the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; 97 cases had follow-up. Also 10 pairs of fresh tissue, seven colorectal cancer cell lines and one normal colon cell line (NCM460).
• Exposure: No asbestos or fiber exposure was studied. The factor studied was the expression level of the gene PDCD2L in tumors.
• Main results:
  • In the databases, PDCD2L expression was up-regulated in various cancers compared with adjacent normal tissues.
  • In the database survival analysis (patients split at median PDCD2L expression), high PDCD2L expression was associated with poor overall survival in ACC (P = 0.04), KICH (P = 0.0075), LAML (P = 0.0032), LGG (P = 0.013), LIHC (P = 0.044), mesothelioma (MESO, P = 0.0077) and UVM (P = 0.016). It was associated with favorable overall survival in UCEC (P = 0.039).
  • PDCD2L expression was not associated with disease-free survival in mesothelioma (MESO), among other cancers.
  • PDCD2L expression across immune subtypes was not statistically different in mesothelioma (MESO), among other cancers.
  • In the hospital samples (126 pairs, immunohistochemistry), PDCD2L was more highly expressed in colorectal cancer tissue than in non-tumor colorectal mucosa.
  • Among colorectal cancer patients, PDCD2L expression was associated with sex (P = 0.002) and histological differentiation (P = 0.041), but not with overall survival or disease-free survival.
  • In the HT29 and SW480 colorectal cancer cell lines, lowering PDCD2L increased the total apoptosis rate and also enhanced cell proliferation.
• The authors' conclusion: The authors concluded that PDCD2L was more highly expressed in colorectal cancer samples than in non-tumor tissue, and that it could serve as a biomarker of colorectal cancer.
• Limitations the authors state:
  • The relationship between PDCD2L expression and the prognosis of colorectal cancer patients needs further study with a larger sample size.
  • How PDCD2L regulates apoptosis-induced proliferation in colorectal cancer needs further investigation.

Topics

Medical terms in this study, explained in our Lexicon: Colorectal Cancer, Apoptosis, Overall Survival, Carcinoma, Mesothelioma, Squamous Cell Carcinoma, Adenocarcinoma, Fibroblast.

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