Non-SMC condensin I complex subunit D2 (NCAPD2) reveals its prognostic and immunologic features in human cancers

Our plain-English summary of Non-SMC condensin I complex subunit D2 (NCAPD2) reveals its prognostic and immunologic features in human cancers, by X. Dong, T. Liu, Z. Li, et al (Aging, 2023).

The study

• Authors: X. Dong, T. Liu, Z. Li, Y. Zhai
• Journal: Aging
• Published: 2023;15(14):7237-7257
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Non-SMC condensin I complex subunit D2 (NCAPD2) is overexpressed in some malignant tumors. However, there are few studies on the function of NCAPD2 in pan-cancer. We used the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN to analyze NCAPD2 expression and promoter methylation levels in 33 tumors and normal samples. We performed immunohistochemistry (IHC) on liver cancer and corresponding normal tissues to examine NCAPD2 protein expression in LIHC. Kaplan-Meier survival and univariate regression analyses were performed to explore the pan-cancer clinical significance of NCAPD2. Moreover, correlative analysis between NCAPD2 expression and clinical characteristics, immune cell infiltration, immune checkpoints, immune regulators, tumor mutation burden (TMB), microsatellite instability (MSI), ribonucleic acid (RNA) methylation regulators, and drug sensitivity was conducted using data from TCGA. We also investigated the effects of NCAPD2 expression on immunotherapy efficacy and prognosis. Gene set enrichment analysis (GSEA) was conducted using NCAPD2. Bioinformatic analysis showed that NCAPD2 was overexpressed in most tumors and correlated with the clinical characteristics of some cancers. IHC results demonstrated that NCAPD2 protein expression was higher in LIHC than in normal liver. NCAPD2 expression was linked with T stage, clinical stage, and histologic grade in LIHC. Overexpression of NCAPD2 resulted in poor overall survival, and disease-specific survival in adrenocortical carcinoma, kidney renal papillary cell carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, lung adenocarcinoma, mesothelioma, pancreatic adenocarcinoma, sarcoma, skin cutaneous melanoma, and uterine corpus endometrial carcinoma. NCAPD2 was considered an independent biomarker by Cox regression in LIHC. The time ROC curve demonstrated that the survival rate of 1-, 3-, and 5-year OS and DSS in LIHC was above 0.6. The expression of NCAPD2 was significantly correlated with immune cell infiltration, immune checkpoints, TMB, MSI, and RNA methylation regulators in several tumors. NCAPD2 had a high predictive value for immunotherapy efficiency in certain tumors. In our study, drugs sensitive to NCAPD2 protein were screened by sensitivity analysis. GSEA analysis showed that NCAPD2 mainly participated in the G2M checkpoint, mitotic spindle, and KRAS-signaling. NCAPD2 may act as a prognostic molecular marker in most cancers.

In plain English

This study did not examine asbestos. It was a computer-based analysis of public cancer databases, mainly The Cancer Genome Atlas, looking at a gene called NCAPD2 across 33 tumor types. One of those types was mesothelioma; the article does not say whether pleural or peritoneal. The authors split patients into high- and low-NCAPD2 groups at the median level. They reported that the gene was more highly expressed than in normal tissue in 25 tumor types. In mesothelioma and nine other cancers, high NCAPD2 was linked with worse overall survival and worse disease-specific survival. The article's text gives no numerical hazard ratios for these links and no count of mesothelioma patients. In mesothelioma, NCAPD2 was not associated with eight immune checkpoint genes. The authors also stained 20 liver cancers from Shengjing Hospital in China and found more NCAPD2 protein than in normal tissue. The authors concluded that NCAPD2 could be regarded as a valuable prognostic biomarker in many tumors. They noted that the results came from public datasets and need experimental confirmation.

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: Pan-cancer bioinformatic analysis of public gene-expression databases, with a small immunohistochemistry (tissue staining) study of liver cancer
• Who was studied: Database expression data for 33 tumor types, including mesothelioma, and normal tissues from TCGA and GTEx. Separately, 20 liver cancers and 10 normal tissues from Shengjing Hospital of China Medical University (15 males, 5 females, aged 30 to 70). No study dates are given.
• Exposure: No asbestos or fiber exposure was studied. The factor examined was the level of NCAPD2 gene expression, split into high and low groups at the median.
• Main results:
  • Across the database tumors, NCAPD2 was highly expressed in 25 tumor types and low in three (LAML, PRAD, THCA), compared with normal tissues.
  • High NCAPD2 expression was associated with poor overall and disease-specific survival in ten cancer types, including mesothelioma (MESO). The hazard ratios are shown only in figures, not in the text.
  • In mesothelioma, NCAPD2 was not associated with any of the eight immune checkpoints examined.
  • Mesothelioma was one of six tumor types listed as exceptions where NCAPD2 was not reported to be associated with stromal, immune or estimate scores.
  • In the hospital liver cancer samples, NCAPD2 protein staining was higher than in normal tissues.
  • In liver hepatocellular carcinoma database patients (187 low-expression, 187 high-expression), NCAPD2 expression was associated with T stage, pathologic stage and histologic grade.
  • For liver hepatocellular carcinoma, time ROC curve values for 1-, 3- and 5-year overall survival were 0.728, 0.631 and 0.608. For disease-specific survival they were 0.784, 0.654 and 0.612.
• The authors' conclusion: The authors concluded that NCAPD2 can be regarded as a valuable prognostic biomarker in many tumors and that its mechanism needs further experimental study.
• Limitations the authors state:
  • Protein expression was checked by staining only in liver cancer.
  • Results came from public datasets, and some findings still need experimental validation.
  • Few studies on NCAPD2 exist, so more experimental work is needed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Microsatellite Instability (MSI-H), Immunotherapy, Prognosis, Overall Survival, Carcinoma, Lung Adenocarcinoma, Mesothelioma.

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