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High temperature requirement A3 (HTRA3) expression predicts postoperative recurrence and survival in patients with non-small-cell lung cancer.

ABSTRACT: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and its recurrence rate after complete resection is high, owing to local or distant metastases. Low expression of high temperature requirement A3 (HTRA3) has been reported to promote tumorigenesis, diminish the effects of anti-tumor treatments, and correlate with a malignant phenotype. To assess the involvement of HTRA3 in the prognosis of postoperative NSCLC, we obtained tumors from 78 patients who had undergone complete surgical resection, and immunohistochemically examined them for HTRA3 expression. HTRA3 was significantly down-regulated in lung cancer tissues compared with normal lung tissues, and only six tumor cases(7.7%) exhibited relatively high levels of HTRA3 (P < 0.001). Notably, high-HTRA3 patients were at significantly lower risk of postoperative recurrence than low-HTRA3 or HTRA3-negative patients (0% versus 31.2% and 35.0%; P = 0.044, 0.029, respectively). High expression of HTRA3 also independently indicated longer disease-free survival in Cox regression analysis (hazard ratio 0.39, 95%CI 0.16-0.95, P = 0.038). Ectopic expression of the long isoform of HTRA3 attenuated the invasion of an NSCLC cell line in a Transwell assay, while knockdown of HTRA3 had the converse effect. Thus, HTRA3 suppresses tumor cell invasiveness and may serve as a prognostic biomarker for postoperative recurrence or survival in NSCLC.

SUBMITTER: Zhao J

PROVIDER: S-EPMC5130039 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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High temperature requirement A3 (HTRA3) expression predicts postoperative recurrence and survival in patients with non-small-cell lung cancer.

Zhao Jingya J Zhang Jing J Zhang Xin X Feng Mingxiang M Qu Jieming J

Oncotarget 20160601 26

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and its recurrence rate after complete resection is high, owing to local or distant metastases. Low expression of high temperature requirement A3 (HTRA3) has been reported to promote tumorigenesis, diminish the effects of anti-tumor treatments, and correlate with a malignant phenotype. To assess the involvement of HTRA3 in the prognosis of postoperative NSCLC, we obtained tumors from 78 patients who had un ...[more]

PMID: 27166271

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Project description:BackgroundThere is currently a lack of effective biomarkers to evaluate efficacy of neoadjuvant therapy (NAT) for resectable non-small cell lung cancer (NSCLC) patients. Circulating tumor DNA (ctDNA) has been investigated as a non-invasive tool for the assessment of tumor burden and minimal residual disease (MRD). The utility of ctDNA profiling in reflecting NAT efficacy, however, has not been confirmed. This study explored the association of ctDNA change with treatment response to NAT and recurrence-free survival (RFS) after surgery.MethodsEligible patients with stage IB-IIIA NSCLC were retrospectively included if they had received neoadjuvant immunotherapy combined with chemotherapy (IO+Chemo), dual immunotherapy (IO+IO), or chemotherapy alone (Chemo). We conducted ctDNA profiling before and after NAT, after surgery, and during follow-ups using an ultra-deep lung cancer-specific MRD (LC-MRD) sequencing panel.ResultsA total of 22 patients who received NAT followed by surgery between August 2018 and July 2019 were included in this study. The major pathological response (MPR) rates were 58.33% (7/12) in the IO+Chemo group, 25.00% (1/4) in the IO+IO group, and 16.67% (1/6) in the Chemo group. The ctDNA dynamics during NAT were highly concordant with pathologic response, demonstrating 100% sensitivity and 83.33% specificity, for an overall accuracy of 91.67%. Pre-surgery detectable ctDNA (after NAT) trended to correlate with inferior RFS [hazard ratio (HR), 7.41; 95% confidence interval (CI): 0.91-60.22, log-rank P=0.03]. At 3-8 days after surgery, ctDNA was detectable in 31.8% of patients and was an independent risk factor for recurrence (HR, 5.37; 95% CI: 1.27-22.67; log-rank P=0.01). The presence of ctDNA at 3 months after surgery showed 83% sensitivity and 90% specificity for predicting relapse (C-index, 0.79; 95% CI: 0.62-0.95). During disease monitoring after surgery, molecular recurrence by means of ctDNA preceded radiographic relapse, with a median time of 6.83 months.ConclusionsThis study investigated the potential of ctDNA in evaluating NAT efficacy in NSCLC, implying the high concordance between ctDNA and pathological response. We also set out the prognostic value of perioperative ctDNA in predicting recurrence.

Dataset Information

High temperature requirement A3 (HTRA3) expression predicts postoperative recurrence and survival in patients with non-small-cell lung cancer.

Publications

High temperature requirement A3 (HTRA3) expression predicts postoperative recurrence and survival in patients with non-small-cell lung cancer.

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