Clinical and Experimental Medicine
Can an endoplasmic-reticulum-stress gene signature stratify overall-survival prognosis in retrospective LUAD transcriptomic cohorts?
The study combined LUAD single-cell and bulk transcriptomic datasets to investigate endoplasmic reticulum stress. Twenty-two survival-associated genes were reduced to a 10-gene ERAS signature using LASSO in TCGA. The authors examined survival stratification in TCGA and seven named GEO datasets, and combined ERAS with age and stage in a nomogram. The reported nomogram AUCs were 0.740, 0.754 and 0.754 at 1, 3 and 5 years. Expression of SERPINH1 and GPR37 was assessed by qPCR in 10 paired tumor and adjacent specimens. Immune scores and drug sensitivities were inferred from molecular data; this does not establish that using ERAS to choose treatment improves outcomes.
Bing Wen, Pengpeng Zhang, Jiping Xie, Zhaokai Zhou, Ge Zhang, Lianmin Zhang, Zhenfa Zhang. Deciphering the prognostic role of endoplasmic reticulum stress in lung adenocarcinoma: integrating prognostic prediction and immunotherapy strategies. Clinical and Experimental Medicine. 2024. https://doi.org/10.1007/s10238-024-01439-4
ERAS: endoplasmic-reticulum-stress gene signatures in lung adenocarcinoma
Retrospective transcriptomic modeling defined a 10-gene ERAS signature, evaluated it across TCGA and GEO datasets, and assessed two model genes in 10 paired LUAD specimens. Treatment-response analyses were computational.
Datasets and specimen pairs are distinct units. No unique pooled participant total is derived. The Results text calls the external survival datasets six but enumerates seven; Methods and Figure 4C identify TCGA plus seven GEO datasets. External evaluation here means retrospective public-dataset assessment, not prospective clinical validation; cross-dataset participant overlap was not independently reconstructed.
Univariate Cox screening followed by LASSO in the TCGA development dataset; public-dataset survival evaluation was not uniformly significant.
| Measure | Value |
|---|---|
| screened prognostic genes | 22 |
| final ERAS genes | 10 |
| named survival datasets | 8 including TCGA |
Source locator: Methods: Dataset source; Results: Model construction and evaluation, Par17; Fig. 4A-C; Supplementary Fig. 1 (MOESM1)
Retrospective nomogram evaluation; these values are not independent prospective performance estimates.
| Measure | Value |
|---|---|
| 1-year AUC | 0.740 |
| 3-year AUC | 0.754 |
| 5-year AUC | 0.754 |
Source locator: Results: Independent prognostic analysis of the ERAS and construction of the nomogram, Par18; Fig. 6F-H
Expression validation only; it does not test survival prediction or treatment effect.
| Measure | Value |
|---|---|
| clinical tissue pairs | 10 |
| genes tested in this qPCR comparison | 2: SERPINH1 and GPR37 |
Source locator: Methods: Clinical specimen collection, Par12; Results: Experimental validation, Par23; Supplementary Fig. 3A-B (MOESM3)
The signature contains 10 genes selected from 22 survival-associated candidates.
Evidence: KF1
The nomogram AUCs were 0.740, 0.754 and 0.754 at 1, 3 and 5 years in the reported retrospective evaluation.
Evidence: KF2
qPCR compared SERPINH1 and GPR37 in 10 paired LUAD tumor and adjacent tissue samples.
Evidence: KF3
| Row ID | Component | Context | Finding | Evidence Level | Scope | Source Locator | Evidence refs |
|---|---|---|---|---|---|---|---|
| evidence-kf1 | A 10-gene ERAS signature was selected from 22 survival-associated genes. | Univariate Cox screening followed by LASSO in the TCGA development dataset; public-dataset survival evaluation was not uniformly significant. | screened prognostic genes: 22; final ERAS genes: 10; named survival datasets: 8 including TCGA | Human transcriptomic associations and limited expression validation | Retrospective LUAD prognostic signature development and public-dataset evaluation. | Methods: Dataset source; Results: Model construction and evaluation, Par17; Fig. 4A-C; Supplementary Fig. 1 (MOESM1) | KF1 |
| evidence-kf2 | The nomogram combining ERAS, age and stage showed the reported time-specific survival discrimination. | Retrospective nomogram evaluation; these values are not independent prospective performance estimates. | 1-year AUC: 0.740; 3-year AUC: 0.754; 5-year AUC: 0.754 | Human transcriptomic associations and limited expression validation | Reported nomogram discrimination within the analyzed data. | Results: Independent prognostic analysis of the ERAS and construction of the nomogram, Par18; Fig. 6F-H | KF2 |
| evidence-kf3 | SERPINH1 and GPR37 expression was higher in LUAD tumor than paired adjacent tissue in the reported qPCR experiment. | Expression validation only; it does not test survival prediction or treatment effect. | clinical tissue pairs: 10; genes tested in this qPCR comparison: 2: SERPINH1 and GPR37 | Human transcriptomic associations and limited expression validation | Limited tumor-adjacent expression validation. | Methods: Clinical specimen collection, Par12; Results: Experimental validation, Par23; Supplementary Fig. 3A-B (MOESM3) | KF3 |
The signature contains 10 genes selected from 22 survival-associated candidates.
Evidence: KF1
The nomogram AUCs were 0.740, 0.754 and 0.754 at 1, 3 and 5 years in the reported retrospective evaluation.
Evidence: KF2
qPCR compared SERPINH1 and GPR37 in 10 paired LUAD tumor and adjacent tissue samples.
Evidence: KF3
No. The reported survival modeling and two-gene expression experiment do not test whether choosing treatment with ERAS improves outcomes.
Evidence: KF1, KF3
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